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肝炎ウイルス･肝がん検診

肝炎ウイルス･

肝がん検診

エビデンスレポート

平成２２年度

がん研究開発費

「がん検診の評価とあり方に関する研究」班

2011 3 31

22

..................................................................................................................................................... 1

............................................................................................................................................ 3

I. ..................................................................................................................................... 4

II. ..................................................................................................................... 6

III. ................................................................................ 11

IV. ............................................................................... 15

1. ....................................................................................................................................... 15 2. ........................................................................................................................... 18 3. ............................................................................................................................................... 18

CQ1. ........................................................... 19 CQ2.

.................................................................................. 23 CQ3.

...................................................................... 24 CQ4. ................................................................................... 26 CQ5. ............................................... 28 CQ6. (B C

) .... 29 CQ7.

.......................................................................... 31 CQ8.

.............................................................................................................................. 37 CQ9. B

.......................................................................... 46 CQ10. B

.......................................................................................................................... 48

V. ........................................................................... 49

VI. ........................................................... 57

VII. ................................... 59

VIII. ....................................................................................................... 62

.................................................................................................................................................. 64

.................................................. 85

.......................................... 86

.................................................................................................................................................. 88

1

42,194 (2005 ) 32,725 (2009

) 4 3

1995

2005 ( 10 ) 30.1 10.1 2009

( 10 ) 19.7 6.6

1)

(B

C )

2)

MEDLINE

1985 1 2009 9 Clinical Question

3)

B

B (hepatitis B virus, HBV) HBV

PCR HBV DNA

B B

B HBV

C

C HCV(hepatitis C virus) PCR HCV

RNA C

C

C

C

C

+

SVR(Sustained Virological Response, )

2

+ C

A.

B.

1 1

14

(chain of evidence)

22

3

1

2

3 ( )

4 ( )

5 B C

6

7

8 Analytic Framework Clinical Questions

1 B

2 C

3 (MEDLINE)

4 (J Dream II )

5 Clinical Question

6

7

8 (B )

9 (C )

10 (C )

11

12

1

2

3 Clinical Question

4

5

4

I.

3 70% HCV1) 14 C

20

22

14

C2, 3)

( )4, 5)

5

1) .

(http://ganjoho.jp/professional/statistics/index.html, 2010.12.28. )

2) C

. C . . 2007.

3) . . . 2009.

4) 12

( ).

. 2001.

5)

17 (2006):

.

6

II.

1. B (hepatitis

B virus, HBV) C (hepatitis C virus, HCV)

6)

HBV HCV7~9)

70% HCV 16% HBs 10)

2. HBV HCV

11) 1995~2000

3,485,648 ( 16~64 2000 16~69 )

HBs HCV HBs 0.63% HCV

0.49% HBs 0.73% 0.53%

(p<0.001) HBs

50~59 16~19 HBs 0.26% 0.20%

50~59 HBs 1.73% 1.35% HCV

0.48% 0.50% HCV

HBs

16~19 HCV 0.11% 0.14% 60~69

HCV 3.45% 3.33% HBs

HCV

2000 15~65

HBV 97 HCV (HCV 70% HCV

RNA ) 88

HBV (genotype) A~J HBV B

genotype B C 10%

80~90% 12, 13) NAT( )

B genotype A

10~20% 14~18) genotype A

genotype A19, 20) HCV genotype 1~6 subtype

1b 60~80% 2a 10~20% 2b 10% 21~28) HBV

7

HCV HBV genotype

A genotype B C HCV genotype 1b genotype

2a 2b 27~31)

3. 42,194 (2005 ) 32,725 (2009

) 4 3 1)

19951) (1981~2003 )

50~59 60~69 70~79 1986 1995

2000 HCV32)

2005

( 10 ) 30.1 10.1 2009 ( 10

) 19.7 6.6 1)

2005 20 65

45~64 ( 1)

2009 20 45~69 55~69

( 2)1) 75

HCV1)

7 1993~1996 5

17.1% 1) 2000

5 23.0%33) 5 34.8%

2.3% 7.8% 1.7%

3 4 34, 35)

HCV

HCV

HBV

40

1.5~2

8

(ICD-10: C22)

80%

94% 10, 36)

6) Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends.

Gastroenterology. 2004; 127(5 Suppl 1): S5-S16.

7) .

(http://epi.ncc.go.jp/jp/can_prev/ , 2011.1.24. )

8) Tanaka K, Tsuji I, Wakai K, Nagata C, Mizoue T, Inoue M, Tsugane S; Research Group for

the Development and Evaluation of Cancer Prevention Strategies in Japan. Cigarette smoking

and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence

among Japanese. Jpn J Clin Oncol. 2006; 36(7): 445-56.


the Development and Evaluation of Cancer Prevention Strategies in Japan. Alcohol drinking


among the Japanese population. Jpn J Clin Oncol. 2008; 38(12): 816-38.

10) Ikai I, Arii S, Okazaki M, Okita K, Omata M, Kojiro M, Takayasu K, Nakanuma Y, Makuuchi

M, Matsuyama Y, Monden M, Kudo M. Report of the 17th Nationwide Follow-up Survey of

Primary Liver Cancer in Japan. Hepatol Res. 2007; 37(9): 676-91.

11) Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R, Suzuki K, Miyakawa Y,

Yoshizawa H. Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated

by the prevalence in the 3,485,648 first-time blood donors during 1995-2000. Intervirology.

2004; 47(1): 32-40.

12) Orito E, Ichida T, Sakugawa H, Sata M, Horiike N, Hino K, Okita K, Okanoue T, Iino S,

Tanaka E, Suzuki K, Watanabe H, Hige S, Mizokami M. Geographic distribution of hepatitis

B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology. 2001;

34(3): 590-4.

13) Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, Suzuki F,

Akuta N, Someya T, Matsuda M, Sato J, Kumada H. Clinical characteristics of patients

infected with hepatitis B virus genotypes A, B, and C. J Gastroenterol. 2002; 37(1): 35-9.

14) Murokawa H, Yoshikawa A, Ohnuma H, Iwata A, Katoh N, Miyamoto M, Mine H, Emura H,

Tadokoro K; Japanese Red Cross NAT Screening Research Group. Epidemiology of blood

donors in Japan, positive for hepatitis B virus and hepatitis C virus by nucleic acid

amplification testing. Vox Sang. 2005; 88(1): 10-6.

15) . HBV HBV

. IASR. 2006; 27(9): 223-4.

9

16) Sugauchi F, Orito E, Ohno T, Tanaka Y, Ozasa A, Kang JH, Toyoda J, Kuramitsu T, Suzuki K,

Tanaka E, Akahane Y, Ichida T, Izumi N, Inoue K, Hoshino H, Iino S, Yotsuyanagi H,

Kakumu S, Tomita E, Okanoue T, Nishiguchi S, Murawaki Y, Hino K, Onji M, Yatsuhashi H,

Sata M, Miyakawa Y, Ueda R, Mizokami M. Spatial and chronological differences in hepatitis

B virus genotypes from patients with acute hepatitis B in Japan. Hepatol Res. 2006; 36(2):

107-14.

17) Hayashi K, Katano Y, Takeda Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Nakano I, Yano M,

Goto H, Yoshioka K, Toyoda H, Kumada T. Comparison of hepatitis B virus subgenotypes in

patients with acute and chronic hepatitis B and absence of lamivudine-resistant strains in

acute hepatitis B in Japan. J Med Virol. 2007;79(4): 366-73.

18) Yoshikawa A, Gotanda Y, Suzuki Y, Tanaka M, Matsukura H, Shiraishi T, Matsubayashi K,

Kon E, Suzuki K, Yugi H; Japanese Red Cross HBV Genotype Research Group. Age- and

gender-specific distributions of hepatitis B virus (HBV) genotypes in Japanese HBV-positive

blood donors. Transfusion. 2009; 49(7): 1314-20.

19) Koibuchi T, Hitani A, Nakamura T, Nojiri N, Nakajima K, Jyuji T, Iwamoto A. Predominance

of genotype A HBV in an HBV-HIV-1 dually positive population compared with an

HIV-1-negative counterpart in Japan. J Med Virol. 2001; 64(4): 435-40.

20) Takeda Y, Katano Y, Hayashi K, Honda T, Yokozaki S, Nakano I, Yano M, Yoshioka K,

Toyoda H, Kumada T, Goto H. Difference of HBV genotype distribution between acute

hepatitis and chronic hepatitis in Japan. Infection. 2006; 34(4): 201-7.

21) Nakao T, Enomoto N, Takada N, Takada A, Date T. Typing of hepatitis C virus genomes by

restriction fragment length polymorphism. J Gen Virol. 1991; 72 (Pt 9): 2105-12.

22) Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F,

Miyakawa Y, et al. Typing hepatitis C virus by polymerase chain reaction with type-specific

primers: application to clinical surveys and tracing infectious sources. J Gen Virol. 1992;

73(Pt 3): 673-9.

23) Takada N, Takase S, Takada A, Date T. HCV genotypes in different countries. Lancet. 1992;

339(8796): 808.

24) Takada N, Takase S, Takada A, Date T. Differences in the hepatitis C virus genotypes in

different countries. J Hepatol. 1993; 17(3): 277-83.

25) Chayama K, Tsubota A, Arase Y, Saitoh S, Koida I, Ikeda K, Matsumoto T, Kobayashi M,

Iwasaki S, Koyama S, et al. Genotypic subtyping of hepatitis C virus. J Gastroenterol Hepatol.

1993; 8(2): 150-6.

26) McOmish F, Yap PL, Dow BC, Follett EA, Seed C, Keller AJ, Cobain TJ, Krusius T, Kolho E,

Naukkarinen R, et al. Geographical distribution of hepatitis C virus genotypes in blood

donors: an international collaborative survey. J Clin Microbiol. 1994; 32(4): 884-92

27) Simmonds P. Variability of hepatitis C virus. Hepatology. 1995; 21(2): 570-83.

10

28) Mondelli MU, Silini E. Clinical significance of hepatitis C virus genotypes. J Hepatol. 1999;

31 Suppl 1: 65-70.

29) Yotsuyanagi H, Okuse C, Yasuda K, Orito E, Nishiguchi S, Toyoda J, Tomita E, Hino K,

Okita K, Murashima S, Sata M, Hoshino H, Miyakawa Y, Iino S; Japanese Acute Hepatitis B

Group. Distinct geographic distributions of hepatitis B virus genotypes in patients with acute

infection in Japan. J Med Virol. 2005; 77(1): 39-46.

30) Suzuki Y, Kobayashi M, Ikeda K, Suzuki F, Arfase Y, Akuta N, Hosaka T, Saitoh S,

Kobayashi M, Someya T, Matsuda M, Sato J, Watabiki S, Miyakawa Y, Kumada H.

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med

Virol. 2005; 76(1): 33-9.

31) Ozasa A, Tanaka Y, Orito E, Sugiyama M, Kang JH, Hige S, Kuramitsu T, Suzuki K, Tanaka

E, Okada S, Tokita H, Asahina Y, Inoue K, Kakumu S, Okanoue T, Murawaki Y, Hino K, Onji

M, Yatsuhashi H, Sakugawa H, Miyakawa Y, Ueda R, Mizokami M. Influence of genotypes

and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.

Hepatology. 2006; 44(2): 326-34.

32) Tanaka H, Imai Y, Hiramatsu N, Ito Y, Imanaka K, Oshita M, Hijioka T, Katayama K,

Yabuuchi I, Yoshihara H, Inoue A, Kato M, Takehara T, Tamura S, Kasahara A, Hayashi N,

Tsukuma H. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to

2003. Ann Intern Med. 2008; 148(11): 820-6.

33) .

71 2004 2000 5 .

. 2008.

34) WHO Cancer Mortality Database. (http://www-dep.iarc.fr/WHOdb/WHOdb.htm, 2010.12.28. )

35) GLOBOCAN 2008. (http://globocan.iarc.fr/, 2010.12.28. )

36) Boyle P and Levin B, editors. World cancer report 2008. IARC: Lyon, 2008.

11

III.

1. 2001 3 12

(

3 )4) I-b

16

( )

HBV B

HBs

HCV

HCV C SVR(Sustained

Virological Response, )

(chain of evidence)

2. 1) B

HBV HBs HBs

HBV

2) C

HCV HCV HCV

1989 NS3-4 (C100-3)

ELISA 64% 37)

1991

NS3 NS4 NS5 HCV

HCV HCV

HCV PCR

TaqMan PCR

12

1.2 LogIU/mL

HCV HBV HCV

38) HCV

37) Uyttendaele S, Claeys H, Mertens W, Verhaert H, Vermylen C. Evaluation of third-generation

screening and con rmatory assays for HCV antibodies. Vox Sang. 1994; 66(2): 122–9.

38) Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. Brief

communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C.

Ann Intern Med. 2008; 149(6): 399-403.

3)

B C

(AFP)

3~6

6~12 AFP

3.

14 18 5

5 (40, 45, 50, 55, 60, 65, 70 5 ) C

B

(

)

19

1)

13

2)

40

ALT (GPT)

14 18

(ALT

)

3)

[ (

) ]

C B15 C HCV

14 19 1 2

39, 40) 14 18 5

C B 14 1.6% 1.3%

18 0.8% 1.0% ( 5)

20 40 40 C B

657,937 660,580 1.0% 1.0%

20

22 201039, 40)

39) . 14~19 . 40) . 20 .

4. 6 41)

1) B

B HBs HBs

HBV

B

14

2) C

C HCV

HCV HCV (NAT)

C

C 2

C

HCV

C

3)

2010 1 6

47 6542)

41) . 19 . (http://www.mhlw.go.jp/houdou/2009/03/h0304-1.html)

42) .

(http://www.ncgm.go.jp/center/index.html) 5.

2008 1

1,822 31

(1.7%) 20

1,000,238 43)

92 (0.009%) 2009

3,008,945 94 (0.003%)44)

43) . 20

. 2010.

44) . 2009 . . 2010; 25(4): 688-734.

15

IV.

1. 45)

7

Analytic Framework( 8) Clinical Question(CQ) CQ

2

CQ

45) 16

( ).

. 2005.

1)

( )

(

)

( )

(

) (

)

CQ

2)

B

C

16

3) Analytic Framework Clinical Question

Analytic Framework

( )

CQ 45) Analytic Framework

CQ

Analytic Framework( 8) B

C

CQ

CQ1.

1) B

2) C

CQ2.

1) B

2) C

3)

CQ3.

CQ4.

1) B

2) C

3)

CQ5.

1) (B C )

2)

CQ6. (B C

)

CQ7.

1) B

2) C

CQ8.

CQ9. B

17

CQ10. B

4)

MEDLINE 1985 1

2009 9

4)

CQ CQ

CQ

CQ

(

)

peer review

( )

5) 45)

2 1 (

1 2 1 )

2 1

CQ B C

18

6)

3

P85

2. 3 4 1985 1

1 CQ MEDLINE3,960 322 J Dream

106 ( 2009 9 19 )

190

2 1 ( 5

) 134 4

CQ ( 5) 1

2

3. CQ CQ

( 3) (

4)

19

CQ1.

1) B

HBV ( )

70~80%

20~30%

HBV HBV

HBs HBe

90% HBV HBV 4

HBe HBV ALT

ALT

HBe HBe

HBe HBs

HBe

HBV

ALT

HBV 10% ALT

HBe HBV DNA

B46) 1980~1995

2,215 ( 1,544 44 ) B 610 ( 475

34 ) 5 10 15 8.0%

21.2% 37.0% F1 0% 8.2% 35.0%

F2 6.2% 16.4% 27.9% F3 17.0% 35.0% 53.7%

5 10 15 2.1% 4.9% 18.8%

F1 0% 2.7% 11.5% F2 0.8% 4.4% 7.1% F3 6.2% 7.7% 34.3%

2,215 1,366 (61.7%)

B

HBV47) 1991~1992 7 30~65 11,893 2000

HBs HBe

(95%CI) HBs HBe 9.6(6.0-15.2) HBs

HBe 60.2(35.5-102.1) HBs

HBe 130 study base

20

nested case-control study HBV DNA (<2.5 pg/mL)

2.5-13.0 pg/mL >13.0 pg/mL (95%CI) 2.3

(0.7-7.3) 6.0 (1.7-21.4) B HBe

HBe HBV DNA

HBV DNA48) 1976~1989 B

217

146 48

( 39 49.5 )

48 nested case-control study

3 ( 3 ) HBV DNA

(<3.7 LGE/mL) 0 (0%) 22 (46%) (p<0.0001)

HBV DNA49)

1991~1992 7 30~65 HBs 3,653

11.4 HBV DNA (<300 copies/mL)

(95%CI) 300-9,999 10,000-99,999

100,000-999,999 1,000,000 copies/mL 1.1 (0.5-2.3) 2.3

(1.1-4.9) 6.6 (3.3-13.1) 6.1 (2.9-12.7) HBe ALT

HBV DNA

HBV

DNA B

2 47, 49)

B

2003

(The Japan Public Health Center-based Prospective Study, JPHC Study) ALT50) 1993~1994 6

68,980 (cohort II) 19,812 ( 6,920 ) 11.8

HBs 499 ALT <30IU/L

(95%CI) ALT 30-69 70 IU/L

18.5 (3.7-93.1) 35.0 (4.2-293.1)

21

HBs ALT

2) C

HCV

1989~1997 C

C 71% (95%CI: 67-74) 51)

CQ1. 1) B

C 1,500 ( 995 49 )46) 5 10 15 8.4%

22.6% 31.3% F1 0% 5.4% 8.8% F2 2.0%

6.1% 15.3% F 3 19.2% 50.2% 67.7% 5 10 15

4.8% 13.6% 26.0% F1 0% 0%

11.3% F2 1.1% 5.6% 14.0% F3 11.0% 29.9% 52.6% B

C

C 152) 1985~1986 35 C (Child-Pugh

A) 214 ( 144

55 ) 114

3.9% 2.9% 2.0% 0.7% 0.1%

(27%) 4.0%

(44%)

31.5%

15.1% 16.6% 27.7% 23 (11%)

1989~1993

(SVR) C

CQ1. 1) B

(JPHC Study) HCV 757 ALT50) ALT

<30IU/L (95%CI) ALT 30-69

70-99 100 IU/L 11.4 (4.7-27.2) 25.1 (9.8-64.8) 35.0 (13.4-91.4)

HBs HCV ALT

46) Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H. Disease progression and hepatocellular

22

carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998; 28(6): 930-8.

47) Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen

CJ; Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the

risk of hepatocellular carcinoma. N Engl J Med. 2002; 347(3):168-74.

48) Ikeda K, Arase Y, Kobayashi M, Someya T, Hosaka T, Saitoh S, Sezaki H, Akuta N, Suzuki F,

Suzuki Y, Kumada H. Hepatitis B virus-related hepatocellular carcinogenesis and its

prevention. Intervirology. 2005; 48(1): 29-38.

49) Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV

Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis

B virus DNA level. JAMA. 2006; 295(1): 65-73.

50) Ishiguro S, Inoue M, Tanaka Y, Mizokami M, Iwasaki M, Tsugane S; JPHC Study Group.

Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based

cohort study in Japan. Eur J Cancer Prev. 2009; 18(1): 26-32.

51) Pagliaro L, Peri V, Linea C, Cammà C, Giunta M, Magrin S. Natural history of chronic

hepatitis C. Ital J Gastroenterol Hepatol. 1999; 31(1): 28-44.

52) Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, Morabito

A, Colombo M. The natural history of compensated cirrhosis due to hepatitis C virus: A

17-year cohort study of 214 patients. Hepatology. 2006; 43(6): 1303-10.

23

CQ2.

1) B B

2) C

C

3)

24

CQ3.

1 1 ( 6) 53) B

(9,373 ) (9,443

) 6 AFP

5 32

10 83.2 54 10 131.5

0.63(95% CI: 0.41-0.98)

HBs

54) 16,652 HBs HCV AFP AST ALT

1 4,843

4,385 458 7

AFP20ng/mL 3 6

1 68

9 0.76(95%CI: 0.38-1.52)

50 HBs AST

AFP 5 self-selection bias

55, 56) 57) lead time

bias

53) Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular

carcinoma. J Cancer Res Clin Oncol. 2004; 130(7): 417-22.

25

54) Chen TH, Chen CJ, Yen MF, Lu SN, Sun CA, Huang GT, Yang PM, Lee HS, Duffy SW.

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk

group in Taiwan. Int J Cancer. 2002; 98(2): 257-61.

55) Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L,

Zanetti M, Sherman M. Surveillance programme of cirrhotic patients for early diagnosis and

treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut. 2001; 48(2): 251-9.

56) , , , , , , ,

. .

. 1990; 88: 63-70.

57) , , , , , , ,

, , . .

. 2008; 46(1): 35-45.

26

CQ4.

1) B

HBs HBs EIA 58, 59) HBs

HBs58, 60) HBV HBs

HBV PCR HBV DNA

PCR

PCR HBV DNA 2.1 (log copy/mL) HBs

HBV DNA PCR occult

HBV HBs HBs61~63)

58) Palmer DR, Perry KR, Mortimer PP, Parry JV. Variation in the sensitivity of HBsAg screening

kits. Transfus Med. 1996; 6(4): 311-7.

59) Motte A, Colson P, Tamalet C. Evaluation of the clinical performance of the Beckman Coulter

Access AbHBsII immunoassay for the detection of hepatitis B surface antibodies. J Clin Virol.

2006; 37(3): 213-7.

60) Shih LN, Sheu JC, Wang JT, Huang GT, Yang PM, Lee HS, Sung JL, Wang TH, Chen DS.

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by

polymerase chain reaction. J Med Virol. 1990; 32(4): 257-60.

61) Gomes SA, Yoshida CF, Niel C. Detection of hepatitis B virus DNA in hepatitis B surface

antigen-negative serum by polymerase chain reaction: evaluation of different primer pairs and

conditions. Acta Virol. 1996; 40(3): 133-8.

62) Togashi H, Hashimoto C, Yokozawa J, Suzuki A, Sugahara K, Saito T, Yamaguchi I, Badawi

H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S. What

can be revealed by extending the sensitivity of HBsAg detection to below the present limit? J

Hepatol. 2008; 49(1): 17-24.

2) C

10 98.9%(95%CI:

94-100) 100% 63)

63) Colin C, Lanoir D, Touzet S, Meyaud-Kraemer L, Bailly F, Trepo C; HEPATITIS Group.

Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an

analysis of the literature. J Viral Hepat. 2001; 8(2): 87-95.

27

3)

64) HBs 1,069 6

AFP AFP 5 ( 26

) 7 71.4% 93.8%

15.1% 65) HCV HBs 602

AFP 6 1 1 7 (

34.5 ) 31 100%

98% 78% 66)

7,022 9 88.9%

99.4% 2.6%

2 AFP

66) 1

64) Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers

of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North

American urban population. Hepatology. 1995; 22(2): 432-8.

65) Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with

chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001; 16(5):

553-9.

66) , , , , .

. . 1995; 33(2): 169-73.

28

CQ5.

1) (B C )

CQ1

2)

67, 68)

67) , , , , ,

1 . . 2009; 71(2):128-30.

68) Erdmann SM, Sachs B, Merk HF. Allergic contact dermatitis due to methyldibromo

glutaronitrile in Euxyl K 400 in an ultrasonic gel. Contact Dermatitis. 2001;44(1): 39-40

29

CQ6. (B C

)

( ) 69~80) 153 69) 68,27671) 1 73) 24 77)

5 7 ( 7)

4

1cm 69)

12 7 70~72, 76, 77, 79, 80)

0.33% 70) 0.51%72) 44%78)

0.14%76) 1.7%70) 10

18.5% 10 10.8%

10 1.35% 10 0.78%

(p=0.508) 77)

(1.9% vs. 1.7%) 73) Tru-cut

(p<0.005) 278)

69) Rivera-Sanfeliz G, Kinney TB, Rose SC, Agha AK, Valji K, Miller FJ, Roberts AC.

Single-pass percutaneous liver biopsy for diffuse liver disease using an automated device:

experience in 154 procedures. Cardiovasc Intervent Radiol. 2005; 28(5): 584-8.

70) Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A. Indications,

methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the

British Society of Gastroenterology and the Royal College of Physicians of London. Gut.

1995; 36(3): 437-41.

71) Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver

biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol. 1986; 2(2): 165-73.

72) Myers RP, Fong A, Shaheen AAM. Utilization rates, complications and costs of percutaneous

liver biopsy: a population-based study including 4275 biopsies. Liver Int. 2008; 28(5):

705-12.

73) Vivas S, Palacio MA, Rodríguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L. Ambulatory

liver biopsy: complications and evolution in 264 cases. Rev Esp Enferm Dig. 1998; 90(3):

175-82.

74) Sugano S, Sumino Y, Hatori T, Mizugami H, Kawafune T, Abei T. Incidence of

30

ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy. Dig Dis Sci.

1991; 36(9): 1229-33.

75) Caturelli E, Giacobbe A, Facciorusso D, Bisceglia M, Villani MR, Siena DA, Fusilli S,

Squillante MM, Andriulli A. Percutaneous biopsy in diffuse liver disease: increasing

diagnostic yield and decreasing complication rate by routine ultrasound assessment of

puncture site. Am J Gastroenterol. 1996; 91(7): 1318-21.

76) Froehlich F, Lamy O, Fried M, Gonvers JJ. Practice and complications of liver biopsy. Results

of a nationwide survey in Switzerland. Dig Dis Sci. 1993; 38(8): 1480-4.

77) van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU. Twenty-year

audit of percutaneous liver biopsy in a major Australian teaching hospital. Intern Med J. 2006;

36(11): 692-9.

78) Lindor KD, Bru C, Jorgensen RA, Rakela J, Bordas JM, Gross JB, Rodes J, McGill DB,

Reading CC, James EM, Charboneau JW, Ludwig J, Batts KP, Zinsmeister AR. The role of

ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy.

Hepatology. 1996; 23(5): 1079-83.

79) Montalto G, Soresi M, Carroccio A, Bascone F, Tripi S, Aragona F, Di Gaetano G,

Notarbartolo A. Percutaneous liver biopsy: a safe outpatient procedure? Digestion. 2001;

63(1): 55-60.

80) Chuah SY, Moody GA, Wicks AC, Mayberry JF. A nationwide survey of liver biopsy--is there

a need to increase resources, manpower and training? Hepatogastroenterology. 1994; 41(1):

4-8.

31

CQ7.

1) B

B 381~83) 1 84) 1 85)

( 8)

1999 84) 1.1

11.5 67 1 (1.5%)

34 4 (12%)

(p=0.043)

(10 : 98%) (10 : 85%) (p=0.018)

1998 85)

B C 637 250

281 29 (10%) 356

66 (19%) (RR: 1.99, 95%CI: 1.09-3.64,

p=0.027)

HCV (RR: 3.14, 95%CI:

1.46-6.77, p=0.004) HBV (RR: 0.98, 95%CI: 0.32-2.92, p=0.97)

2001 81) B

7

7 2 5

B

(RD:

-4.8%, 95%CI: -11.1 1.5, )

B

2 6 (n=1,303)83)

(RD: -5.0%, 95%CI: -9.4 -0.5, p=0.028)

(RD: -8.5%, 95%CI: -13.6 -3.6, p=0.0012) (RD: -0.5%, 95%CI:

-4.9 4.0, p=0.84) HBe

B

32

HBV

(genotype)

81) Cammà C, Giunta M, Andreone P, Craxì A. Interferon and prevention of hepatocellular

carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol. 2001; 34(4): 593-602.

82) Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B

infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008; 28(9):

1067-77.

83) Miyake Y, Kobashi H, Yamamoto K. Meta-analysis: the effect of interferon on development

of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J

Gastroenterol. 2009; 44(5): 470-5.

84) Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon

therapy in patients with chronic hepatitis B virus infection. Hepatology. 1999; 29(3): 971-5.

85) International Interferon-alpha Hepatocellular Carcinoma Study Group. Effect of

interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective

cohort study. Lancet. 1998; 351(9115): 1535-9.

2) C

HCV

+ +

A.

C

1 81) 3 86, 87, 90) 11 85,

88, 89, 91~98) ( 9) Cammà C

(RD: -12.8%, 95%CI: -8.3 -17.2, p<0.0001)

(RD: -10%, 95%CI: -5.9 -14.2, p<0.0001) 81)

(SVR)

+ 2 87, 94) Azzaroli 60 C

33

2 30 + 1

30 (p<0.004)

C +

SVR

+

+ SVR

+

B.

C

C ( )

1 3 ( 10)

Cammà C

(RD: -3.6%, 95%CI: -2.3 -5.0, p<0.00001)

Inoue 99) C 2,890

4.3 224 5 699

101 Cox

C (HR: 0.31, p=0.015)

Yoshida 89)

(OR: 0.516, p<0.001) Ikeda 98) C

1,643 5.1

1,191 28 452 67

C

(HR: 0.6, p=0.10)

296, 100)

Gramenzi C

Kasahara C

34

(SMR:2.7, 95%CI: 2.0-3.6)

(SMR: 0.9, 95%CI: 0.7-1.1) 101)

C

C

352 14.4

158 110 (69.6%) 102)

C ( )

2 100, 103) 1 104)

104)

2 C

86) Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S,

Kobayashi K, Otani S. Randomised trial of effects of interferon-alpha on incidence of

hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;

346(8982): 1051-5.

87) Azzaroli F, Accogli E, Nigro G, Trere D, Giovanelli S, Miracolo A, Lodato F, Montagnani M,

Tamé M, Colecchia A, Mwangemi C, Festi D, Roda E, Derenzini M, Mazzella G. Interferon

plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study

on patients with HCV related cirrhosis. World J Gastroenterol. 2004; 10(21): 3099-102.

88) Benvegnù L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A. Retrospective

analysis of the effect of interferon therapy on the clinical outcome of patients with viral

cirrhosis. Cancer. 1998; 83(5): 901-9.

89) Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M,

Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata

M; IHIT Study Group. Interferon therapy reduces the risk for hepatocellular carcinoma:

national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in

Japan. Ann Intern Med. 1999; 131(3): 174-81.

90) Valla DC, Chevallier M, Marcellin P, Payen JL, Trepo C, Fonck M, Bourliere M, Boucher E,

Miguet JP, Parlier D, Lemonnier C, Opolon P. Treatment of hepatitis C virus-related cirrhosis:

a randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology. 1999;

29(6): 1870-5.

91) Mazzella G, Accogli E, Sottili S, Festi D, Orsini M, Salzetta A, Novelli V, Cipolla A, Fabbri C,

35

Pezzoli A, Roda E. Alpha interferon treatment may prevent hepatocellular carcinoma in

HCV-related liver cirrhosis. J Hepatol. 1996; 24(2): 141-7.

92) Ikeda K, Arase Y, Saitoh S, Kobayashi M, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki F,

Suzuki Y, Kumada H. Anticarcinogenic impact of interferon on patients with chronic hepatitis

C: a large-scale long-term study in a single center. Intervirology. 2006; 49(1-2): 82-90.

93) Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E,

Hirota K, Yoshida H, Ohashi Y, Omata M; Tokyo-Chiba Hepatitis Research Group. Antiviral

therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma

development and improved survival. Ann Intern Med. 2005; 142(2): 105-14.

94) Yu ML, Lin SM, Chuang WL, Dai CY, Wang JH, Lu SN, Sheen IS, Chang WY, Lee CM,

Liaw YF. A sustained virological response to interferon or interferon/ribavirin reduces

hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide,

multicentre study in Taiwan. Antivir Ther. 2006; 11(8): 985-94.

95) Ikeda K, Arase Y, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Kobayashi M,

Saitoh S, Suzuki F, Suzuki Y, Kumada H. Necessities of interferon therapy in elderly patients

with chronic hepatitis C. Am J Med. 2009; 122(5): 479-86.

96) Gramenzi A, Andreone P, Fiorino S, Cammà C, Giunta M, Magalotti D, Cursaro C, Calabrese

C, Arienti V, Rossi C, Di Febo G, Zoli M, Craxì A, Gasbarrini G, Bernardi M. Impact of

interferon therapy on the natural history of hepatitis C virus related cirrhosis. Gut. 2001;

48(6): 843-8.

97) Soga K, Shibasaki K, Aoyagi Y. Effect of interferon on incidence of hepatocellular carcinoma

in patients with chronic hepatitis C. Hepatogastroenterology. 2005; 52(64): 1154-8.

98) Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Nakamura I,

Murashima N, Kumada H, Kawanishi M. Effect of interferon therapy on hepatocellular

carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of

1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology.

1999; 29(4): 1124-30.

99) Inoue A, Tsukuma H, Oshima A, Yabuuchi T, Nakao M, Matsunaga T, Kojima J, Tanaka S.

Effectiveness of interferon therapy for reducing the incidence of hepatocellular carcinoma

among patients with type C chronic hepatitis. J Epidemiol. 2000; 10(4): 234-40.

100) Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM,

Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL;

HALT-C Trial Investigators. Prolonged therapy of advanced chronic hepatitis C with low-dose

peginterferon. N Engl J Med. 2008; 359(23): 2429-41.

101) Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E,

Hino K, Hayashi K, Tamura S, Itoh Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N.

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as

36

well as virological responses by preventing liver-related death. J Viral Hepat. 2004; 11(2):

148-56.

102) Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A,

Silini EM, Almasio PL, Maisonneuve P. Predicting mortality risk in patients with

compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol.

2009; 104(5): 1147-58.

103) Fartoux L, Degos F, Trépo C, Goria O, Calès P, Tran A, Buffet C, Poynard T, Capron D,

Raabe JJ, Roulot D, Naveau S, Grange JD, Poupon RE, Poupon R, Serfaty L. Effect of

prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a

randomized trial. Clin Gastroenterol Hepatol. 2007; 5(4): 502-7.

104) Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, Hosaka T, Sezaki H, Yatsuji H,

Kawamura Y, Kobayashi M, Kumada H. Prolonged-interferon therapy reduces

hepatocarcinogenesis in aged-patients with chronic hepatitis C. J Med Virol. 2007; 79(8):

1095-102.

37

CQ8.

HCV

C

105~109)

-2a( )+ -2b( )+

11

-2a+ : (73.4%) (69.3%) (62.8%) (38.2%)

(22.1%) (43.2%) (31.7%) (31.2%) (24.1%) (29.6%)

(36.7%) ( )(30.2%) (60.3%) (46.2%) (40.7%)

(26.1%) (92.5%) (89.4%) (84.9%)

(82.9%) (81.4%) (73.4%) (65.8%)

(36.7%) (27.1%) (23.6%)

-2b+ : (95.5%) (93.4%) (88.6%) (66.0%)

(96.7%) (95.8%) (87.3%) (85.5%)

(79.8%) (78.6%) (70.8%) (81.9%)

(54.8%) (51.8%) (68.7%) (53.3%) (52.7%) (75.6%)

(68.4%)

+

+

66 (126 17,831 ) 102)

31

(95%CI) 5.30%(95%CI: 4.97-5.64) 0.17%(95%CI: 0.12-0.25)

0.035%(95%CI: 0.013-0.076)

105) Koskinas J, Merkouraki P, Manesis E, Hadziyannis S. Assessment of depression in patients

with chronic hepatitis: effect of interferon treatment. Dig Dis. 2002; 20(3-4): 284-8.

106) Kanda Y, Shigeno K, Matsuo H, Yano M, Yamada N, Kumagami H. Interferon-induced

sudden hearing loss. Audiology. 1995; 34(2): 98-102.

107) Del Monte P, Bernasconi D, De Conca V, Randazzo M, Meozzi M, Badaracco B, Mesiti S,

38

Marugo M. Endocrine evaluation in patients treated with interferon-alpha for chronic hepatitis

C. Horm Res. 1995; 44(3): 105-9.

108) Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E. Influence of psychiatric

diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. Am J

Gastroenterol. 2001; 96(1): 157-64.

109) Martín-Santos R, Díez-Quevedo C, Castellví P, Navinés R, Miquel M, Masnou H, Soler A,

Ardevol M, García F, Galeras JA, Planas R, Solà R. De novo depression and anxiety disorders

and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients

with hepatitis C. Aliment Pharmacol Ther. 2008; 27(3): 257-65.

110) Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, Jacobs S, Clement RP; The

Hepatitis C Intervention Therapy Group. A dose-ranging study of pegylated interferon alfa-2b

and ribavirin in chronic hepatitis C. Hepatology. 2000; 32(3): 647-53.

111) Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman

ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with

interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

Lancet. 2001; 358(9286): 958-65.

112) Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D,

Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus

ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347(13): 975-82.

113) Bosques-Padilla F, Trejo-Estrada R, Campollo-Rivas O, Cortez-Hernández C,

Dehesa-Violante M, Maldonado-Garza H, Pérez-Gómez R, Cabrera-Valdespino A.

Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of

Mexican patients included in a multicenter international clinical trial. Ann Hepatol. 2003;

2(3): 135-9.

114) Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN,

Mayet I, Khan MQ, Kessie G. Peginterferon alpha-2b plus ribavirin compared with interferon

alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly

infected with genotype 4. Liver Int. 2004; 24(6): 568-74.

115) Bruno S, Cammà C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D,

Colombo M, Craxì A, Mondelli MU, Pinzello G. Peginterferon alfa-2b plus ribavirin for naïve

patients with genotype 1 chronic hepatitis C: a randomized controlled trial. J Hepatol. 2004;

41(3): 474-81.

116) Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G,

Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM;

PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination

therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.

Ann Intern Med. 2004; 140(5): 346-55.

39

117) Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R, Siddique I, Al-Nakib B.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine]

for the treatment of non-responders to standard interferon and ribavirin. Antivir Ther. 2004;

9(4): 499-503.

118) Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS,

Morgan TR, Bonkovsky HL, Lee WM, Dienstag JL, Ghany MG, Goodman ZD, Everhart JE;

Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group. Peginterferon

alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

Gastroenterology. 2004; 126(4): 1015-23; discussion 947.

119) Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N,

O'Brien CB, Lamour F, Lardelli P; PEGASYS Study NR16071 Investigator Group.

Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and

normal aminotransferase levels. Gastroenterology. 2004; 127(6): 1724-32.

120) Herrine SK, Brown RS Jr, Bernstein DE, Ondovik MS, Lentz E, Te H. Peginterferon alpha-2a

combination therapies in chronic hepatitis C patients who relapsed after or had a viral

breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of

efficacy and safety. Dig Dis Sci. 2005; 50(4): 719-26.

121) Jacobson IM, Gonzalez SA, Ahmed F, Lebovics E, Min AD, Bodenheimer HC Jr, Esposito SP,

Brown RS Jr, Bräu N, Klion FM, Tobias H, Bini EJ, Brodsky N, Cerulli MA, Aytaman A,

Gardner PW, Geders JM, Spivack JE, Rahmin MG, Berman DH, Ehrlich J, Russo MW, Chait

M, Rovner D, Edlin BR. A randomized trial of pegylated interferon alpha-2b plus ribavirin in

the retreatment of chronic hepatitis C. Am J Gastroenterol. 2005; 100(11): 2453-62.

122) Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz

AA, Madwar MA. Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C

genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

Gut. 2005; 54(6): 858-66.

123) Lee SD, Yu ML, Cheng PN, Lai MY, Chao YC, Hwang SJ, Chang WY, Chang TT, Hsieh TY,

Liu CJ, Chen DS. Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and

interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in

Taiwan. J Viral Hepat. 2005; 12(3): 283-91.

124) Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tamé MR, Montagnani M, Muratori R,

Giovanelli S, Feletti V, Bacchi Reggiani ML, Roda E, Mazzella G. Higher doses of

peginterferon alpha-2b administered twice weekly improve sustained virological response in

difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study. J Viral

Hepat. 2005; 12(5): 536-42.

125) Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca

D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b

40

and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005; 352(25):

2609-17.

126) von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A,

Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and

ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.

Gastroenterology. 2005; 129(2): 522-7.

127) Zeuzem S, Pawlotsky JM, Lukasiewicz E, von Wagner M, Goulis I, Lurie Y, Gianfranco E,

Vrolijk JM, Esteban JI, Hezode C, Lagging M, Negro F, Soulier A, Verheij-Hart E, Hansen B,

Tal R, Ferrari C, Schalm SW, Neumann AU; DITTO-HCV Study Group. International,

multicenter, randomized, controlled study comparing dynamically individualized versus

standard treatment in patients with chronic hepatitis C. J Hepatol. 2005; 43(2): 250-7.

128) Abergel A, Hezode C, Leroy V, Barange K, Bronowicki JP, Tran A, Alric L, Castera L,

Bernard PH, Henquell C, Lafeuille H, Ughetto S, Darcha C, Chevallier M, Martineau N,

Dubost S, Randl K, Dhumeaux D, Bommelaer G, Bonny C; French multicenter study group.

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis:

a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b. J

Viral Hepat. 2006; 13(12): 811-20.

129) Berg C, Goncales FL Jr, Bernstein DE, Sette H Jr, Rasenack J, Diago M, Jensen DM, Graham

P, Cooksley G. Re-treatment of chronic hepatitis C patients after relapse: efficacy of

peginterferon-alpha-2a (40 kDa) and ribavirin. J Viral Hepat. 2006; 13(7): 435-40.

130) Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T,

Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth

U, Zeuzem S. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus

72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006; 130(4): 1086-97.

131) Brandão C, Barone A, Carrilho F, Silva A, Patelli M, Caramori C, Focaccia R, Pereira L,

Pedroso M, Tatsch F, Pessoa M; Pegasys Brazilian Study Group. The results of a randomized

trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and

ribavirin combination therapy in patients with chronic hepatitis C genotype 1. J Viral Hepat.

2006; 13(8): 552-9.

132) Bronowicki JP, Ouzan D, Asselah T, Desmorat H, Zarski JP, Foucher J, Bourlière M, Renou C,

Tran A, Melin P, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F,

Lonjon-Domanec I, Pawlotsky JM. Effect of ribavirin in genotype 1 patients with hepatitis C

responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology. 2006; 131(4):

1040-8.

133) Ciancio A, Picciotto A, Giordanino C, Smedile A, Tabone M, Manca A, Marenco G,

Garbagnoli P, Andreoni M, Cariti G, Calleri G, Sartori M, Cusumano S, Grasso A, Rizzi R,

Gallo M, Basso M, Anselmo M, Percario G, Ciccone G, Rizzetto M, Saracco G. A

41

randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in

the re-treatment of patients with chronic hepatitis C not responding to standard interferon and

ribavirin. Aliment Pharmacol Ther. 2006; 24(7): 1079-86.

134) Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, Hubmann R, Datz C,

Stauber R, Steindl-Munda P, Kessler HH, Klingler A, Gangl A; Austrian Hepatitis Study

Group. Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD)

plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C

genotype 1 infection. J Hepatol. 2006; 44(2): 275-82.

135) Meyer-Wyss B, Rich P, Egger H, Helbling B, Müllhaupt B, Rammert C, Gonvers JJ, Oneta C,

Criblez D, Rossi L, Borovicka J, Meyenberger C, Arn M, Renner EL; Swiss Association for

the Study of the Liver (SASL). Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5

microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and

up to moderate fibrosis. J Viral Hepat. 2006; 13(7): 457-65.

136) Yenice N, Mehtap O, Gümrah M, Arican N. The efficacy of pegylated interferon alpha 2a or

2b plus ribavirin in chronic hepatitis C patients. Turk J Gastroenterol. 2006; 17(2): 94-8.

137) Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang

WY, Chuang WL. A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b

plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan.

Liver Int. 2006; 26(1): 73-81.

138) Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O,

Noviello S, Brass C, Albrecht J. Efficacy of 24 weeks treatment with peginterferon alfa-2b

plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low

pretreatment viremia. J Hepatol. 2006; 44(1): 97-103.

139) Carr C, Hollinger FB, Yoffe B, Wakil A, Phillips J, Bzowej N, Leung J, Mirro K, Poordad F,

Moore DH, Gish RG. Efficacy of interferon alpha-2b induction therapy before retreatment for

chronic hepatitis C. Liver Int. 2007; 27(8): 1111-8.

140) Diago M, Crespo J, Olveira A, Pérez R, Bárcena R, Sánchez-Tapias JM, Muñoz-Sánchez M,

Romero-Gómez M. Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment

with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true

non-responder patients. Aliment Pharmacol Ther. 2007; 26(8): 1131-8.

141) Diago M, Olveira A, Solá R, Romero-Gómez M, Moreno-Otero R, Pérez R, Salmerón J,

Enríquez J, Planas R, Gavilán JC, Del Olmo J, Uribarrena R, Sillero C, Benítez A,

Sánchez-Galdón S, Dalmau B, Eraña L, Montoro M, Portu J, Garijo JM, Barniol R,

Domínguez A, Rota R, Olcoz JL, Antón M, Pamplona X, Casanovas T, Jiménez E, Huarte M,

Díaz F, Sánchez-Ruano J, Orive M, Muñoz-Sánchez M, Roset M. Treatment of chronic

hepatitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine

clinical practice in Spain: early prediction of sustained virological response rate. Aliment

42

Pharmacol Ther. 2007; 25(8): 899-906.

142) Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K,

Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M. Pegylated

interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of

rapid and early virologic response. Hepatology. 2007; 46(6): 1732-40.

143) Kuboki M, Iino S, Okuno T, Omata M, Kiyosawa K, Kumada H, Hayashi N, Sakai T.

Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic hepatitis C in

Japanese patients. J Gastroenterol Hepatol. 2007; 22(5): 645-52.

144) Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V,

Bengtsson L, McNair L, Alam J. Phase 2 study of the combination of merimepodib with

peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic

hepatitis C. J Hepatol. 2007; 47(4): 476-83.

145) Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and

ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology. 2007; 46(6):

1688-94.

146) Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, Luketic VA, Sanyal

AJ. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and

epoetin alpha. Hepatology. 2007; 46(2): 371-9.

147) Sjogren MH, Sjogren R Jr, Lyons MF, Ryan M, Santoro J, Smith C, Reddy KR, Bonkovsky H,

Huntley B, Faris-Young S. Antiviral response of HCV genotype 1 to consensus interferon and

ribavirin versus pegylated interferon and ribavirin. Dig Dis Sci. 2007; 52(6): 1540-7.

148) Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh

MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin

for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007; 56(4):

553-9.

149) Angelico M, Koehler-Horst B, Piccolo P, Angelico F, Gentile S, Francioso S, Tarquini P,

Vecchia RD, Ponti L, Pilleri G, Barlattani A, Grieco A, Soccorsi F, Guarascio P, Demelia L,

Sorbello O, Rossi Z, Forlini G, Zaru S, Bandiera F; SMIEC II Investigators. Peginterferon

alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological

responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin

and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve

patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2008; 20(7): 680-7.

150) Bain VG, Lee SS, Peltekian K, Yoshida EM, Deschênes M, Sherman M, Bailey R,

Witt-Sullivan H, Balshaw R, Krajden M; Canadian PEGASYS Study Group. Clinical trial:

exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection

treated with peginterferon alpha-2a plus ribavirin. Aliment Pharmacol Ther. 2008; 28(1):

43-50.

43

151) Lagging M, Langeland N, Pedersen C, Färkkilä M, Buhl MR, Mørch K, Dhillon AP, Alsiö A,

Hellstrand K, Westin J, Norkrans G; NORDynamIC Study Group. Randomized comparison of

12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype

2/3 infection. Hepatology. 2008; 47(6): 1837-45.

152) Napoli N, Giannelli G, Antonaci A, Antonaci S. The use of different Peg-interferon alpha-2b

regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not

affect the achievement of sustained virological response. J Viral Hepat. 2008; 15(4): 300-4.

153) Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, Bellia V, Del Poggio P,

Fornaciari G, Ceriani R, Ramella G, Corradi C, Rossini A, Bruno S; Gruppo Epatologico

Lombardo. Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated

treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.

Antivir Ther. 2008; 13(5): 663-73.

154) Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G.

Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active

chronic hepatitis: a pilot study. J Interferon Cytokine Res. 2008; 28(10): 623-9.

155) Sood A, Midha V, Hissar S, Kumar M, Suneetha PV, Bansal M, Sood N, Sakhuja P, Sarin SK.

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon

in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian

experience. J Gastroenterol Hepatol. 2008; 23(2): 203-7.

156) Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, Naoumov NV. Clinical

trial: individualized treatment duration for hepatitis C virus genotype 1 with

peginterferon-alpha 2a plus ribavirin. Aliment Pharmacol Ther. 2008; 27(9): 810-9.

157) von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, Hinrichsen H,

Weidenbach H, Gerken G, Manns M, Buggisch P, Herrmann E, Zeuzem S. Placebo-controlled

trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in

chronic hepatitis C virus-1 infection. Hepatology. 2008; 48(5): 1404-11.

158) Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC,

Hsieh MY, Wang LY, Chang WY, Chuang WL. Rapid virological response and treatment

duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology. 2008;

47(6): 1884-93.

159) Zeuzem S, Yoshida EM, Benhamou Y, Pianko S, Bain VG, Shouval D, Flisiak R, Rehak V,

Grigorescu M, Kaita K, Cronin PW, Pulkstenis E, Subramanian GM, McHutchison JG.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with

genotype 1 chronic hepatitis C. Hepatology. 2008; 48(2): 407-17.

160) Andriulli A, Cursaro C, Cozzolongo R, Iacobellis A, Valvano MR, Mangia A, Minerva N,

Bacca D, Stanzione M, Scuteri A, Montalto G, Andreone P. Early discontinuation of ribavirin

in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin. J Viral

44

Hepat. 2009; 16(1): 28-35.

161) Bressler B, Wang K, Grippo JF, Heathcote EJ. Pharmacokinetics and response of obese

patients with chronic hepatitis C treated with different doses of PEG-IFN alpha-2a (40KD)

(PEGASYS). Br J Clin Pharmacol. 2009; 67(3): 280-7.

162) Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourlière M,

Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam

J, Pawlotsky JM, Zeuzem S; PROVE2 Study Team. Telaprevir and peginterferon with or

without ribavirin for chronic HCV infection. N Engl J Med. 2009; 360(18): 1839-50.

163) Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, Sata M. A randomized study of

extended treatment with peginterferon alpha-2b plus ribavirin based on time to HCV RNA

negative-status in patients with genotype 1b chronic hepatitis C. Am J Gastroenterol. 2009;

104(1): 70-5.

164) Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandão-Mello CE, Reddy

KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A. Re-treatment of

patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized

trial. Ann Intern Med. 2009; 150(8): 528-40.

165) Kawaoka T, Kawakami Y, Tsuji K, Ito H, Kitamoto M, Aimitsu S, Kawakami H, Jeong SC,

Imamura M, Aikata H, Takahashi S, Chayama K. Dose comparison study of pegylated

interferon-alpha-2b plus ribavirin in naïve Japanese patients with hepatitis C virus genotype 2:

a randomized clinical trial. J Gastroenterol Hepatol. 2009; 24(3): 366-71.

166) Langlet P, D'Heygere F, Henrion J, Adler M, Delwaide J, Van Vlierberghe H, Mulkay JP,

Lasser L, Brenard R, Horsmans Y, Michielsen P, Laureys A, Nevens F. Clinical trial: a

randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in

treatment-naïve or relapsing chronic hepatitis C patients. Aliment Pharmacol Ther. 2009;

30(4): 352-63.

167) McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee

WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K,

Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team.

Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J

Med. 2009; 361(6): 580-93.

168) Roberts SK, Weltman MD, Crawford DH, McCaughan GW, Sievert W, Cheng WS,

Rawlinson W, Desmond PV, Marks PS, Yoshihara M, Rizkalla B, Depamphilis JK, Dore GJ;

Chariot Study Group. Impact of high-dose peginterferon alfa-2A on virological response rates

in patients with hepatitis C genotype 1: a randomized controlled trial. Hepatology. 2009;

50(4): 1045-55.

169) Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB. Improved virologic response in chronic

hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin.

45


170) Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson

L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S,

McHutchison JG; MErimepodib TRiple cOmbination Study Group. Merimepodib, pegylated

interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin

nonresponders. Hepatology. 2009; 50(6): 1719-26.

171) Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, Atsumi H,

Nakano S, Arakawa T. Eight-week regimen of antiviral combination therapy with

peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus

genotype 2 and a rapid virological response. Liver Int. 2009; 29(1): 120-5.

172) Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP,

Marino-Marsilia G, Fontanella L, Leandro G. Peginterferon alfa-2a plus ribavirin is more

effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus

infection. Gastroenterology. 2010; 138(1): 116-22.

173) Brady DE, Torres DM, An JW, Ward JA, Lawitz E, Harrison SA. Induction pegylated

interferon alfa-2b in combination with ribavirin in patients with genotypes 1 and 4 chronic

hepatitis C: a prospective, randomized, multicenter, open-label study. Clin Gastroenterol

Hepatol. 2010; 8(1): 66-71.e1.

174) Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L. Pioglitazone

improves virological response to peginterferon alpha-2b/ribavirin combination therapy in

hepatitis C genotype 4 patients with insulin resistance. Liver Int. 2010; 30(3): 447-54.

175) Mecenate F, Pellicelli AM, Barbaro G, Romano M, Barlattani A, Mazzoni E, Bonaventura ME,

Nosotti L, Arcuri P, Picardi A, Barbarini G, D'Ambrosio C, Paffetti A, Andreoli A, Soccorsi F;

Club Epatologi Ospedalieri (CLEO) Group. Short versus standard treatment with pegylated

interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo

trial. BMC Gastroenterol. 2010; 10: 21.

176) Méndez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Morán S, Juarez JA,

Chung RT, Dehesa-Violante M. A randomized controlled trial of double versus triple therapy

with amantadine for genotype 1 chronic hepatitis C in Latino patients. Dig Dis Sci. 2010;

55(9): 2629-35.

177) Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E,

Russo A, Colombo M. Randomized study of peginterferon-alpha2a plus ribavirin vs

peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology. 2010; 138(1):

108-15.

178) , , , , , . C

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Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study

Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J

Med. 2004; 351(15): 1521-31.

180) Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai

CL. Long-term lamivudine therapy reduces the risk of long-term complications of chronic

hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007; 12(8):

1295-303.

181) Papatheodoridis GV, Dimou E, Dimakopoulos K, Manolakopoulos S, Rapti I, Kitis G,

Tzourmakliotis D, Manesis E, Hadziyannis SJ. Outcome of hepatitis B e antigen-negative

chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.

Hepatology. 2005; 42(1): 121-9.


Kawamura Y, Kobayashi M, Kumada H. Comparison of interferon and lamivudine treatment

in Japanese patients with HBeAg positive chronic hepatitis B. J Med Virol. 2007; 79(9):

1286-92.

183) Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks

I, Kane RL, Wilt TJ. Antiviral therapy for adults with chronic hepatitis B: a systematic review

for a National Institutes of Health Consensus Development Conference. Ann Intern Med.

2009; 150(2): 111-24.

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184) Tramarin A, Gennaro N, Compostella FA, Gallo C, Wendelaar Bonga LJ, Postma MJ. HCV

screening to enable early treatment of hepatitis C: a mathematical model to analyse costs and

outcomes in two populations. Curr Pharm Des. 2008; 14(17): 1655-60.

185) Nakamura J, Terajima K, Aoyagi Y, Akazawa K. Cost-effectiveness of the national screening

55

program for hepatitis C virus in the general population and the high-risk groups. Tohoku J

Exp Med. 2008; 215(1): 33-42.

186) Loubière S, Rotily M, Moatti JP. Prevention could be less cost-effective than cure: the case of

hepatitis C screening policies in France. Int J Technol Assess Health Care. 2003; 19(4):

632-45.

187) Singer ME, Younossi ZM. Cost effectiveness of screening for hepatitis C virus in

asymptomatic, average-risk adults. Am J Med. 2001; 111(8): 614-21.

188) . . . 1999;

46(6): 447-65.

189) Jusot JF, Colin C. Cost-effectiveness analysis of strategies for hepatitis C screening in French

blood recipients. Eur J Public Health. 2001; 11(4): 373-9.

190) Saab S, Brezina M, Gitnick G, Martin P, Yee HF Jr. Hepatitis C screening strategies in

hemodialysis patients. Am J Kidney Dis. 2001; 38(1): 91-7.

191) Leal P, Stein K, Rosenberg W. What is the cost utility of screening for hepatitis C virus (HCV)

in intravenous drug users? J Med Screen. 1999; 6(3): 124-31.

192) Veldhuijzen IK, Toy M, Hahné SJ, De Wit GA, Schalm SW, de Man RA, Richardus JH.

Screening and early treatment of migrants for chronic hepatitis B virus infection is

cost-effective. Gastroenterology. 2010; 138(2): 522-30.

193) Kang JY, Lee TP, Yap I, Lun KC. Analysis of cost-effectiveness of different strategies for

hepatocellular carcinoma screening in hepatitis B virus carriers. J Gastroenterol Hepatol.

1992; 7(5): 463-8.

194) Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, Jackson S, Ryder

S, Price A, Stein K. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review

and economic analysis. Health Technol Assess. 2007; 11(34): 1-206.

195) Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U. Cost-effectiveness of hepatocellular

carcinoma surveillance in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol

Hepatol. 2005; 3(1):75-84.

196) Nakamura J, Toyabe SI, Aoyagi Y, Akazawa K. Economic impact of extended treatment with

peginterferon alpha-2a and ribavirin for slow hepatitis C virologic responders. J Viral Hepat.

2008; 15(4): 293-9.

197) Nakamura J, Kobayashi K, Toyabe S, Aoyagi Y, Akazawa K. The cost-effectiveness of the

new protocol reflecting rapid virologic response to peginterferon alpha-2b and ribavirin for

chronic hepatitis C. Eur J Gastroenterol Hepatol. 2007; 19(9): 733-9.

198) Hayashida K, Nagasue I, Fukuda T, Gunji A. The natural history model of hepatitis C virus

infection and the economic evaluation of alpha interferon treatment. J Epidemiol. 2002; 12(1):

22-32.

199) Ishida H, Wong JB, Hino K, Kurokawa F, Nishina S, Sakaida I, Okita K, Tamesa T, Oka M,

56

Torimura T, Sata M, Takahashi S, Chayama K, Inoue Y. Validating a Markov model of

treatment for hepatitis C virus-related hepatocellular carcinoma. Methods Inf Med. 2008;

47(6): 529-40.

57

VI.

USPSTF(U.S. Preventive Servises Task Force) NCI(National Cancer Institute)

CISNET (Cancer Intervention and Surveillance Modeling Network)

2008

2 50~75

10 5 S +200)

2009 40 75

6

CISNET 50~69

16.5%( 15% 23%) 40

50 3%( 1% 6%)

70

201)

40 Age trial 10202)

USPSTF

58

CISNET

200) Zauber AG, Vogelaar IL, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM.

Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S.

Preventive Services Task Force. Ann Intern Med. 2008; 149(9): 659-69.

201) Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, Huang H, Lee SJ,

Munsell M, Plevritis SK, Ravdin P, Schechter CB, Sigal B, Stoto MA, Stout NK, van

Ravesteyn NT, Venier J, Zelen M, Feuer EJ; Breast Cancer Working Group of the Cancer

Intervention and Surveillance Modeling Network (CISNET). Effects of Mammography

Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and

Harms. Ann Intern Med. 2009; 151(10): 738-47.

202) Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group.

Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’

follow-up: a randomized controlled trial. Lancet. 2006; 368(9552): 2053-60.

59

VII.

AFP

1)

(

)

USPSTF(U.S. Preventive Servises Task Force) HBV203~206) HCV

207, 208)

2005209)

2002

NIH consensus meeting 210)

Veterans Affires HCV211)

CDC (Centers for Disease Control and Prevention) 2001

National Hepatitis C Prevention Strategy

212)

WHO/Europe HEN(Health Evidence Network)

HIV213)

2)

40 HBs HCV

6 AFP

(

) 214)

2002 AHRQ(Agency for Healthcare Research and Quality)

AFP215) NCI/PDQ(National Cancer Institute/Physician Data Query)

AFP

60

216)

203) U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy:

U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern

Med. 2009; 150(12): 869-73, W154.

204) Lin K, Vickery J. Screening for hepatitis B virus infection in pregnant women: evidence for

the U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern

Med. 2009; 150(12): 874-6.

205) U.S. Preventive Services Task Force. Screening for Hepatitis B Virus Infection: A Brief

Evidence Update for the U.S. Preventive Services Task Force. AHRQ Pub. No. 05-0552-B.

February 2004.

206) U.S. Preventive Services Task Force. Screening for Hepatitis B Virus Infection:

Recommendation Statement. AHRQ Pub. No. 05-0552-A. 3 February 2004.

207) U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults:

recommendation statement. Ann Intern Med. 2004; 140(6): 462-4.

208) Chou R, Clark EC, Helfand M; U.S. Preventive Services Task Force. Screening for hepatitis C

virus infection: a review of the evidence for the U.S. Preventive Services Task Force. Ann

Intern Med. 2004; 140(6): 465-79.

209) Hill L, Henry B, Schweikert S; Prevention Practice Committee, American College of

Preventive Medicine. Screening for chronic hepatitis C: American College of Preventive

Medicine practice policy statement. Am J Prev Med. 2005; 28(3): 327-30.

210) NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci

Statements. 2002 Jun 10-12; 19(3): 1-46.

211) VA National Clinical Public Health Programs. Hepatitis C Topics: Hepatitis C Testing and

Prevention Counseling Guidelines for VA Health Care Practitioners.

(http://www.hepatitis.va.gov/vahep?page=prtop05-gd-01&pf=doc-pf&pp=pf)

212) CDC(Centers for Disease Control and Prevention). National Hepatitis C Prevention Strategy.

2001.

213) WHO/Europe Health Evidence Network (HEN) synthesis report. What is the evidence for the

effectiveness of interventions to reduce hepatitis C infection and the associated morbidity?

2005.

214) Yoo KY. Cancer control activities in the Republic of Korea. Jpn J Clin Oncol. 2008; 38(5):

327-33.

215) Evidence Report /Technology Assessment, Number 60. Management of Chronic Hepatitis C.

AHRQ Pub. No. 02-E030. July 2002.

216) National Cancer Institute. Liver (Hepatocellular) Cancer Screening (PDQ®). Health

Professional Version.

61

(http://www.cancer.gov/cancertopics/pdq/screening/hepatocellular/healthprofessional/allpages

/print)

62

VIII.

C

C

10

C

QOL

(chain of evidence)

1

( )

63

Analytic Framework

(chain of evidence)

NICE(National Institute for Health and Clinical Excellence)

64

1) .

(http://ganjoho.jp/professional/statistics/index.html, 2010.12.28. )

2) C

. C . . 2007.

3) . . . 2009.

4) 12

( ).

. 2001.

5)

17 (2006):

.

6) Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends.

Gastroenterology. 2004; 127(5 Suppl 1): S5-S16.

7) .

(http://epi.ncc.go.jp/jp/can_prev/ , 2011.1.24. )


the Development and Evaluation of Cancer Prevention Strategies in Japan. Cigarette smoking


among Japanese. Jpn J Clin Oncol. 2006; 36(7): 445-56.


the Development and Evaluation of Cancer Prevention Strategies in Japan. Alcohol drinking


among the Japanese population. Jpn J Clin Oncol. 2008; 38(12): 816-38.

10) Ikai I, Arii S, Okazaki M, Okita K, Omata M, Kojiro M, Takayasu K, Nakanuma Y, Makuuchi

M, Matsuyama Y, Monden M, Kudo M. Report of the 17th Nationwide Follow-up Survey of

Primary Liver Cancer in Japan. Hepatol Res. 2007; 37(9): 676-91.

11) Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R, Suzuki K, Miyakawa Y,

Yoshizawa H. Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated

by the prevalence in the 3,485,648 first-time blood donors during 1995-2000. Intervirology.

2004; 47(1): 32-40.

12) Orito E, Ichida T, Sakugawa H, Sata M, Horiike N, Hino K, Okita K, Okanoue T, Iino S,

Tanaka E, Suzuki K, Watanabe H, Hige S, Mizokami M. Geographic distribution of hepatitis

B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology. 2001;

34(3): 590-4.

65

13) Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, Suzuki F,

Akuta N, Someya T, Matsuda M, Sato J, Kumada H. Clinical characteristics of patients

infected with hepatitis B virus genotypes A, B, and C. J Gastroenterol. 2002; 37(1): 35-9.

14) Murokawa H, Yoshikawa A, Ohnuma H, Iwata A, Katoh N, Miyamoto M, Mine H, Emura H,

Tadokoro K; Japanese Red Cross NAT Screening Research Group. Epidemiology of blood

donors in Japan, positive for hepatitis B virus and hepatitis C virus by nucleic acid

amplification testing. Vox Sang. 2005; 88(1): 10-6.

15) . HBV HBV

. IASR. 2006; 27(9): 223-4.

16) Sugauchi F, Orito E, Ohno T, Tanaka Y, Ozasa A, Kang JH, Toyoda J, Kuramitsu T, Suzuki K,

Tanaka E, Akahane Y, Ichida T, Izumi N, Inoue K, Hoshino H, Iino S, Yotsuyanagi H,

Kakumu S, Tomita E, Okanoue T, Nishiguchi S, Murawaki Y, Hino K, Onji M, Yatsuhashi H,

Sata M, Miyakawa Y, Ueda R, Mizokami M. Spatial and chronological differences in hepatitis

B virus genotypes from patients with acute hepatitis B in Japan. Hepatol Res. 2006; 36(2):

107-14.

17) Hayashi K, Katano Y, Takeda Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Nakano I, Yano M,

Goto H, Yoshioka K, Toyoda H, Kumada T. Comparison of hepatitis B virus subgenotypes in

patients with acute and chronic hepatitis B and absence of lamivudine-resistant strains in

acute hepatitis B in Japan. J Med Virol. 2007; 79(4): 366-73.

18) Yoshikawa A, Gotanda Y, Suzuki Y, Tanaka M, Matsukura H, Shiraishi T, Matsubayashi K,

Kon E, Suzuki K, Yugi H; Japanese Red Cross HBV Genotype Research Group. Age- and

gender-specific distributions of hepatitis B virus (HBV) genotypes in Japanese HBV-positive

blood donors. Transfusion. 2009; 49(7): 1314-20.

19) Koibuchi T, Hitani A, Nakamura T, Nojiri N, Nakajima K, Jyuji T, Iwamoto A. Predominance

of genotype A HBV in an HBV-HIV-1 dually positive population compared with an

HIV-1-negative counterpart in Japan. J Med Virol. 2001; 64(4): 435-40.

20) Takeda Y, Katano Y, Hayashi K, Honda T, Yokozaki S, Nakano I, Yano M, Yoshioka K,

Toyoda H, Kumada T, Goto H. Difference of HBV genotype distribution between acute

hepatitis and chronic hepatitis in Japan. Infection. 2006; 34(4): 201-7.

21) Nakao T, Enomoto N, Takada N, Takada A, Date T. Typing of hepatitis C virus genomes by

restriction fragment length polymorphism. J Gen Virol. 1991; 72(Pt 9): 2105-12.

22) Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Sato K, Tsuda F,

Miyakawa Y, et al. Typing hepatitis C virus by polymerase chain reaction with type-specific

primers: application to clinical surveys and tracing infectious sources. J Gen Virol. 1992;

73(Pt 3): 673-9.

23) Takada N, Takase S, Takada A, Date T. HCV genotypes in different countries. Lancet. 1992;

66

339(8796): 808.

24) Takada N, Takase S, Takada A, Date T. Differences in the hepatitis C virus genotypes in

different countries. J Hepatol. 1993; 17(3): 277-83.

25) Chayama K, Tsubota A, Arase Y, Saitoh S, Koida I, Ikeda K, Matsumoto T, Kobayashi M,

Iwasaki S, Koyama S, et al. Genotypic subtyping of hepatitis C virus. J Gastroenterol Hepatol.

1993; 8(2): 150-6.

26) McOmish F, Yap PL, Dow BC, Follett EA, Seed C, Keller AJ, Cobain TJ, Krusius T, Kolho E,

Naukkarinen R, et al. Geographical distribution of hepatitis C virus genotypes in blood

donors: an international collaborative survey. J Clin Microbiol. 1994; 32(4): 884-92.

27) Simmonds P. Variability of hepatitis C virus. Hepatology. 1995; 21(2): 570-83.

28) Mondelli MU, Silini E. Clinical significance of hepatitis C virus genotypes. J Hepatol. 1999;

31 Suppl 1: 65-70.

29) Yotsuyanagi H, Okuse C, Yasuda K, Orito E, Nishiguchi S, Toyoda J, Tomita E, Hino K,

Okita K, Murashima S, Sata M, Hoshino H, Miyakawa Y, Iino S; Japanese Acute Hepatitis B

Group. Distinct geographic distributions of hepatitis B virus genotypes in patients with acute

infection in Japan. J Med Virol. 2005; 77(1): 39-46.

30) Suzuki Y, Kobayashi M, Ikeda K, Suzuki F, Arfase Y, Akuta N, Hosaka T, Saitoh S,

Kobayashi M, Someya T, Matsuda M, Sato J, Watabiki S, Miyakawa Y, Kumada H.

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med

Virol. 2005; 76(1): 33-9.

31) Ozasa A, Tanaka Y, Orito E, Sugiyama M, Kang JH, Hige S, Kuramitsu T, Suzuki K, Tanaka

E, Okada S, Tokita H, Asahina Y, Inoue K, Kakumu S, Okanoue T, Murawaki Y, Hino K, Onji

M, Yatsuhashi H, Sakugawa H, Miyakawa Y, Ueda R, Mizokami M. Influence of genotypes

and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.

Hepatology. 2006; 44(2): 326-34.

32) Tanaka H, Imai Y, Hiramatsu N, Ito Y, Imanaka K, Oshita M, Hijioka T, Katayama K,

Yabuuchi I, Yoshihara H, Inoue A, Kato M, Takehara T, Tamura S, Kasahara A, Hayashi N,

Tsukuma H. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to

2003. Ann Intern Med. 2008; 148(11): 820-6.

33) .

71 2004 2000 5 .

. 2008.

34) WHO Cancer Mortality Database.

(http://www-dep.iarc.fr/WHOdb/WHOdb.htm, 2010.12.28. )

35) GLOBOCAN 2008.

(http://globocan.iarc.fr/, 2010.12.28. )

67

36) Boyle P and Levin B, editors. World cancer report 2008. IARC: Lyon, 2008.

37) Uyttendaele S, Claeys H, Mertens W, Verhaert H, Vermylen C. Evaluation of third-generation

screening and confirmatory assays for HCV antibodies. Vox Sang. 1994; 66(2): 122-9.

38) Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. Brief

communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C.

Ann Intern Med. 2008; 149(6): 399-403.

39) . 14~19 .

40) . 20 .

41) . 19 .

(http://www.mhlw.go.jp/houdou/2009/03/h0304-1.html)

42) .

(http://www.ncgm.go.jp/center/index.html)

43) . 20

. 2010.

44) . 2009 . . 2010; 25(4): 688-734.

45) 16

( ).

. 2005.

46) Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama

K, Murashima N, Kumada H. Disease progression and hepatocellular carcinogenesis in

patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol.

1998; 28(6): 930-8.

47) Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen

CJ; Taiwan Community-Based Cancer Screening Project Group. Hepatitis B e antigen and the

risk of hepatocellular carcinoma. N Engl J Med. 2002; 347(3):168-74.

48) Ikeda K, Arase Y, Kobayashi M, Someya T, Hosaka T, Saitoh S, Sezaki H, Akuta N, Suzuki F,

Suzuki Y, Kumada H. Hepatitis B virus-related hepatocellular carcinogenesis and its

prevention. Intervirology. 2005; 48(1): 29-38.

49) Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV

Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis

B virus DNA level. JAMA. 2006; 295(1): 65-73.

50) Ishiguro S, Inoue M, Tanaka Y, Mizokami M, Iwasaki M, Tsugane S; JPHC Study Group.

Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based

cohort study in Japan. Eur J Cancer Prev. 2009; 18(1): 26-32.

51) Pagliaro L, Peri V, Linea C, Cammà C, Giunta M, Magrin S. Natural history of chronic

hepatitis C. Ital J Gastroenterol Hepatol. 1999; 31(1): 28-44.

68

52) Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, Morabito

A, Colombo M. The natural history of compensated cirrhosis due to hepatitis C virus: A

17-year cohort study of 214 patients. Hepatology. 2006; 43(6): 1303-10.

53) Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular

carcinoma. J Cancer Res Clin Oncol. 2004; 130(7): 417-22.

54) Chen TH, Chen CJ, Yen MF, Lu SN, Sun CA, Huang GT, Yang PM, Lee HS, Duffy SW.

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk

group in Taiwan. Int J Cancer. 2002; 98(2): 257-61.

55) Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L,

Zanetti M, Sherman M. Surveillance programme of cirrhotic patients for early diagnosis and

treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut. 2001; 48(2): 251-9.

56)

.

. 1990; 88: 63-70.

57)

.

. 2008; 46(1): 35-45.

58) Palmer DR, Perry KR, Mortimer PP, Parry JV. Variation in the sensitivity of HBsAg screening

kits. Transfus Med. 1996; 6(4): 311-7.

59) Motte A, Colson P, Tamalet C. Evaluation of the clinical performance of the Beckman Coulter

Access AbHBsII immunoassay for the detection of hepatitis B surface antibodies. J Clin Virol.

2006; 37(3): 213-7.

60) Shih LN, Sheu JC, Wang JT, Huang GT, Yang PM, Lee HS, Sung JL, Wang TH, Chen DS.

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by

polymerase chain reaction. J Med Virol. 1990; 32(4): 257-60.

61) Gomes SA, Yoshida CF, Niel C. Detection of hepatitis B virus DNA in hepatitis B surface

antigen-negative serum by polymerase chain reaction: evaluation of different primer pairs and

conditions. Acta Virol. 1996; 40(3): 133-8.

62) Togashi H, Hashimoto C, Yokozawa J, Suzuki A, Sugahara K, Saito T, Yamaguchi I, Badawi

H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S. What

can be revealed by extending the sensitivity of HBsAg detection to below the present limit? J

Hepatol. 2008; 49(1): 17-24.

63) Colin C, Lanoir D, Touzet S, Meyaud-Kraemer L, Bailly F, Trepo C; HEPATITIS Group.

Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an

analysis of the literature. J Viral Hepat. 2001; 8(2): 87-95.

64) Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers

69

of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North

American urban population. Hepatology. 1995; 22(2): 432-8.

65) Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with

chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001; 16(5):

553-9.

66) , , , , .

. . 1995; 33(2):169-73.

67) , , , , , .

1 . . 2009; 71(2): 128-30.

68) Erdmann SM, Sachs B, Merk HF. Allergic contact dermatitis due to methyldibromo

glutaronitrile in Euxyl K 400 in an ultrasonic gel. Contact Dermatitis. 2001; 44(1): 39-40.

69) Rivera-Sanfeliz G, Kinney TB, Rose SC, Agha AK, Valji K, Miller FJ, Roberts AC.

Single-pass percutaneous liver biopsy for diffuse liver disease using an automated device:

experience in 154 procedures. Cardiovasc Intervent Radiol. 2005; 28(5): 584-8.

70) Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A. Indications,

methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the

British Society of Gastroenterology and the Royal College of Physicians of London. Gut.

1995; 36(3): 437-41.

71) Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver

biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol. 1986; 2(2): 165-73.

72) Myers RP, Fong A, Shaheen AAM. Utilization rates, complications and costs of percutaneous

liver biopsy: a population-based study including 4275 biopsies. Liver Int. 2008; 28(5):

705-12.

73) Vivas S, Palacio MA, Rodríguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L. Ambulatory

liver biopsy: complications and evolution in 264 cases. Rev Esp Enferm Dig. 1998; 90(3):

175-82.

74) Sugano S, Sumino Y, Hatori T, Mizugami H, Kawafune T, Abei T. Incidence of

ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy. Dig Dis Sci.

1991; 36(9): 1229-33.

75) Caturelli E, Giacobbe A, Facciorusso D, Bisceglia M, Villani MR, Siena DA, Fusilli S,

Squillante MM, Andriulli A. Percutaneous biopsy in diffuse liver disease: increasing

diagnostic yield and decreasing complication rate by routine ultrasound assessment of

puncture site. Am J Gastroenterol. 1996; 91(7): 1318-21.

76) Froehlich F, Lamy O, Fried M, Gonvers JJ. Practice and complications of liver biopsy. Results

of a nationwide survey in Switzerland. Dig Dis Sci. 1993; 38(8): 1480-4.

77) van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU. Twenty-year

70

audit of percutaneous liver biopsy in a major Australian teaching hospital. Intern Med J. 2006;

36(11): 692-9.

78) Lindor KD, Bru C, Jorgensen RA, Rakela J, Bordas JM, Gross JB, Rodes J, McGill DB,

Reading CC, James EM, Charboneau JW, Ludwig J, Batts KP, Zinsmeister AR. The role of

ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy.

Hepatology. 1996; 23(5): 1079-83.

79) Montalto G, Soresi M, Carroccio A, Bascone F, Tripi S, Aragona F, Di Gaetano G,

Notarbartolo A. Percutaneous liver biopsy: a safe outpatient procedure? Digestion. 2001;

63(1): 55-60.

80) Chuah SY, Moody GA, Wicks AC, Mayberry JF. A nationwide survey of liver biopsy--is there

a need to increase resources, manpower and training? Hepatogastroenterology. 1994; 41(1):

4-8.

81) Cammà C, Giunta M, Andreone P, Craxì A. Interferon and prevention of hepatocellular

carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol. 2001; 34(4): 593-602.

82) Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: Treatment of hepatitis B

infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008; 28(9):

1067-77.

83) Miyake Y, Kobashi H, Yamamoto K. Meta-analysis: the effect of interferon on development

of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J

Gastroenterol. 2009; 44(5): 470-5.

84) Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon

therapy in patients with chronic hepatitis B virus infection. Hepatology. 1999; 29(3): 971-5.

85) International Interferon-alpha Hepatocellular Carcinoma Study Group. Effect of

interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective

cohort study. Lancet. 1998; 351(9115): 1535-9.

86) Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S,

Kobayashi K, Otani S. Randomised trial of effects of interferon-alpha on incidence of

hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;

346(8982): 1051-5.

87) Azzaroli F, Accogli E, Nigro G, Trere D, Giovanelli S, Miracolo A, Lodato F, Montagnani M,

Tamé M, Colecchia A, Mwangemi C, Festi D, Roda E, Derenzini M, Mazzella G. Interferon

plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study

on patients with HCV related cirrhosis. World J Gastroenterol. 2004; 10(21): 3099-102.

88) Benvegnù L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A. Retrospective

analysis of the effect of interferon therapy on the clinical outcome of patients with viral

cirrhosis. Cancer. 1998; 83(5): 901-9.

71

89) Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M,

Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata

M; IHIT Study Group. Interferon therapy reduces the risk for hepatocellular carcinoma:

national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in

Japan. Ann Intern Med. 1999; 131(3): 174-81.

90) Valla DC, Chevallier M, Marcellin P, Payen JL, Trepo C, Fonck M, Bourliere M, Boucher E,

Miguet JP, Parlier D, Lemonnier C, Opolon P. Treatment of hepatitis C virus-related cirrhosis:

a randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology. 1999;

29(6): 1870-5.

91) Mazzella G, Accogli E, Sottili S, Festi D, Orsini M, Salzetta A, Novelli V, Cipolla A, Fabbri C,

Pezzoli A, Roda E. Alpha interferon treatment may prevent hepatocellular carcinoma in

HCV-related liver cirrhosis. J Hepatol. 1996; 24(2): 141-7.

92) Ikeda K, Arase Y, Saitoh S, Kobayashi M, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki F,

Suzuki Y, Kumada H. Anticarcinogenic impact of interferon on patients with chronic hepatitis

C: a large-scale long-term study in a single center. Intervirology. 2006; 49(1-2): 82-90.

93) Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E,

Hirota K, Yoshida H, Ohashi Y, Omata M; Tokyo-Chiba Hepatitis Research Group. Antiviral

therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma

development and improved survival. Ann Intern Med. 2005; 142(2): 105-14.

94) Yu ML, Lin SM, Chuang WL, Dai CY, Wang JH, Lu SN, Sheen IS, Chang WY, Lee CM,

Liaw YF. A sustained virological response to interferon or interferon/ribavirin reduces

hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide,

multicentre study in Taiwan. Antivir Ther. 2006; 11(8): 985-94.

95) Ikeda K, Arase Y, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Kobayashi M,

Saitoh S, Suzuki F, Suzuki Y, Kumada H. Necessities of interferon therapy in elderly patients

with chronic hepatitis C. Am J Med. 2009; 122(5): 479-86.

96) Gramenzi A, Andreone P, Fiorino S, Cammà C, Giunta M, Magalotti D, Cursaro C, Calabrese

C, Arienti V, Rossi C, Di Febo G, Zoli M, Craxì A, Gasbarrini G, Bernardi M. Impact of

interferon therapy on the natural history of hepatitis C virus related cirrhosis. Gut. 2001;

48(6): 843-8.

97) Soga K, Shibasaki K, Aoyagi Y. Effect of interferon on incidence of hepatocellular carcinoma

in patients with chronic hepatitis C. Hepatogastroenterology. 2005; 52(64): 1154-8.

98) Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Nakamura I,

Murashima N, Kumada H, Kawanishi M. Effect of interferon therapy on hepatocellular

carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of

1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology.

72

1999; 29(4): 1124-30.

99) Inoue A, Tsukuma H, Oshima A, Yabuuchi T, Nakao M, Matsunaga T, Kojima J, Tanaka S.

Effectiveness of interferon therapy for reducing the incidence of hepatocellular carcinoma

among patients with type C chronic hepatitis. J Epidemiol. 2000; 10(4): 234-40.

100) Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM,

Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL;

HALT-C Trial Investigators. Prolonged therapy of advanced chronic hepatitis C with low-dose

peginterferon. N Engl J Med. 2008; 359(23): 2429-41.

101) Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E,

Hino K, Hayashi K, Tamura S, Itoh Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N.

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as

well as virological responses by preventing liver-related death. J Viral Hepat. 2004; 11(2):

148-56.

102) Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A,

Silini EM, Almasio PL, Maisonneuve P. Predicting mortality risk in patients with

compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol.

2009; 104(5): 1147-58.

103) Fartoux L, Degos F, Trépo C, Goria O, Calès P, Tran A, Buffet C, Poynard T, Capron D,

Raabe JJ, Roulot D, Naveau S, Grange JD, Poupon RE, Poupon R, Serfaty L. Effect of

prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a

randomized trial. Clin Gastroenterol Hepatol. 2007; 5(4): 502-7.


Kawamura Y, Kobayashi M, Kumada H. Prolonged-interferon therapy reduces

hepatocarcinogenesis in aged-patients with chronic hepatitis C. J Med Virol. 2007; 79(8):

1095-102.

105) Koskinas J, Merkouraki P, Manesis E, Hadziyannis S. Assessment of depression in patients

with chronic hepatitis: effect of interferon treatment. Dig Dis. 2002; 20(3-4): 284-8.

106) Kanda Y, Shigeno K, Matsuo H, Yano M, Yamada N, Kumagami H. Interferon-induced

sudden hearing loss. Audiology. 1995; 34(2): 98-102.

107) Del Monte P, Bernasconi D, De Conca V, Randazzo M, Meozzi M, Badaracco B, Mesiti S,

Marugo M. Endocrine evaluation in patients treated with interferon-alpha for chronic hepatitis

C. Horm Res. 1995; 44(3): 105-9.

108) Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E. Influence of psychiatric

diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. Am J

Gastroenterol. 2001; 96(1): 157-64.

109) Martín-Santos R, Díez-Quevedo C, Castellví P, Navinés R, Miquel M, Masnou H, Soler A,

73

Ardevol M, García F, Galeras JA, Planas R, Solà R. De novo depression and anxiety disorders

and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients

with hepatitis C. Aliment Pharmacol Ther. 2008; 27(3): 257-65.

110) Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, Jacobs S, Clement RP; The

Hepatitis C Intervention Therapy Group. A dose-ranging study of pegylated interferon alfa-2b

and ribavirin in chronic hepatitis C. Hepatology. 2000; 32(3): 647-53.

111) Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman

ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with

interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

Lancet. 2001; 358(9286): 958-65.

112) Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D,

Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus

ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347(13): 975-82.

113) Bosques-Padilla F, Trejo-Estrada R, Campollo-Rivas O, Cortez-Hernández C,

Dehesa-Violante M, Maldonado-Garza H, Pérez-Gómez R, Cabrera-Valdespino A.

Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of

Mexican patients included in a multicenter international clinical trial. Ann Hepatol. 2003;

2(3): 135-9.

114) Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN,

Mayet I, Khan MQ, Kessie G. Peginterferon alpha-2b plus ribavirin compared with interferon

alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly

infected with genotype 4. Liver Int. 2004; 24(6): 568-74.

115) Bruno S, Cammà C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D,

Colombo M, Craxì A, Mondelli MU, Pinzello G. Peginterferon alfa-2b plus ribavirin for naïve

patients with genotype 1 chronic hepatitis C: a randomized controlled trial. J Hepatol. 2004;

41(3): 474-81.

116) Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G,

Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM;

PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination

therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.

Ann Intern Med. 2004; 140(5): 346-55

117) Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R, Siddique I, Al-Nakib B.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine]

for the treatment of non-responders to standard interferon and ribavirin. Antivir Ther. 2004;

9(4): 499-503.

118) Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS,

74

Morgan TR, Bonkovsky HL, Lee WM, Dienstag JL, Ghany MG, Goodman ZD, Everhart JE;

Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group. Peginterferon

alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

Gastroenterology. 2004; 126(4): 1015-23; discussion 947.

119) Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N,

O'Brien CB, Lamour F, Lardelli P; PEGASYS Study NR16071 Investigator Group.

Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and

normal aminotransferase levels. Gastroenterology. 2004; 127(6): 1724-32.

120) Herrine SK, Brown RS Jr, Bernstein DE, Ondovik MS, Lentz E, Te H. Peginterferon alpha-2a

combination therapies in chronic hepatitis C patients who relapsed after or had a viral

breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of

efficacy and safety. Dig Dis Sci. 2005; 50(4): 719-26.

121) Jacobson IM, Gonzalez SA, Ahmed F, Lebovics E, Min AD, Bodenheimer HC Jr, Esposito SP,

Brown RS Jr, Bräu N, Klion FM, Tobias H, Bini EJ, Brodsky N, Cerulli MA, Aytaman A,

Gardner PW, Geders JM, Spivack JE, Rahmin MG, Berman DH, Ehrlich J, Russo MW, Chait

M, Rovner D, Edlin BR. A randomized trial of pegylated interferon alpha-2b plus ribavirin in

the retreatment of chronic hepatitis C. Am J Gastroenterol. 2005; 100(11): 2453-62.

122) Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz

AA, Madwar MA. Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C

genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

Gut. 2005; 54(6): 858-66.

123) Lee SD, Yu ML, Cheng PN, Lai MY, Chao YC, Hwang SJ, Chang WY, Chang TT, Hsieh TY,

Liu CJ, Chen DS. Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and

interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in

Taiwan. J Viral Hepat. 2005; 12(3): 283-91.

124) Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tamé MR, Montagnani M, Muratori R,

Giovanelli S, Feletti V, Bacchi Reggiani ML, Roda E, Mazzella G. Higher doses of

peginterferon alpha-2b administered twice weekly improve sustained virological response in

difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study. J Viral

Hepat. 2005; 12(5): 536-42.

125) Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca

D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b

and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005; 352(25):

2609-17.

126) von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A,

Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and

75

ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.


127) Zeuzem S, Pawlotsky JM, Lukasiewicz E, von Wagner M, Goulis I, Lurie Y, Gianfranco E,

Vrolijk JM, Esteban JI, Hezode C, Lagging M, Negro F, Soulier A, Verheij-Hart E, Hansen B,

Tal R, Ferrari C, Schalm SW, Neumann AU; DITTO-HCV Study Group. International,

multicenter, randomized, controlled study comparing dynamically individualized versus

standard treatment in patients with chronic hepatitis C. J Hepatol. 2005; 43(2): 250-7.

128) Abergel A, Hezode C, Leroy V, Barange K, Bronowicki JP, Tran A, Alric L, Castera L,

Bernard PH, Henquell C, Lafeuille H, Ughetto S, Darcha C, Chevallier M, Martineau N,

Dubost S, Randl K, Dhumeaux D, Bommelaer G, Bonny C; French multicenter study group.

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis:

a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b. J

Viral Hepat. 2006; 13(12): 811-20.

129) Berg C, Goncales FL Jr, Bernstein DE, Sette H Jr, Rasenack J, Diago M, Jensen DM, Graham

P, Cooksley G. Re-treatment of chronic hepatitis C patients after relapse: efficacy of

peginterferon-alpha-2a (40 kDa) and ribavirin. J Viral Hepat. 2006; 13(7): 435-40.

130) Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T,

Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth

U, Zeuzem S. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus

72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006; 130(4): 1086-97.

131) Brandão C, Barone A, Carrilho F, Silva A, Patelli M, Caramori C, Focaccia R, Pereira L,

Pedroso M, Tatsch F, Pessoa M; Pegasys Brazilian Study Group. The results of a randomized

trial looking at 24 weeks vs. 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and

ribavirin combination therapy in patients with chronic hepatitis C genotype 1. J Viral Hepat.

2006; 13(8): 552-9.

132) Bronowicki JP, Ouzan D, Asselah T, Desmorat H, Zarski JP, Foucher J, Bourlière M, Renou C,

Tran A, Melin P, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F,

Lonjon-Domanec I, Pawlotsky JM. Effect of ribavirin in genotype 1 patients with hepatitis C

responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology. 2006; 131(4):

1040-8.

133) Ciancio A, Picciotto A, Giordanino C, Smedile A, Tabone M, Manca A, Marenco G,

Garbagnoli P, Andreoni M, Cariti G, Calleri G, Sartori M, Cusumano S, Grasso A, Rizzi R,

Gallo M, Basso M, Anselmo M, Percario G, Ciccone G, Rizzetto M, Saracco G. A

randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in

the re-treatment of patients with chronic hepatitis C not responding to standard interferon and

ribavirin. Aliment Pharmacol Ther. 2006; 24(7): 1079-86.

76

134) Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, Hubmann R, Datz C,

Stauber R, Steindl-Munda P, Kessler HH, Klingler A, Gangl A; Austrian Hepatitis Study

Group. Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD)

plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C

genotype 1 infection. J Hepatol. 2006; 44(2): 275-82.

135) Meyer-Wyss B, Rich P, Egger H, Helbling B, Müllhaupt B, Rammert C, Gonvers JJ, Oneta C,

Criblez D, Rossi L, Borovicka J, Meyenberger C, Arn M, Renner EL; Swiss Association for

the Study of the Liver (SASL). Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5

microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and

up to moderate fibrosis. J Viral Hepat. 2006; 13(7): 457-65.

136) Yenice N, Mehtap O, Gümrah M, Arican N. The efficacy of pegylated interferon alpha 2a or

2b plus ribavirin in chronic hepatitis C patients. Turk J Gastroenterol. 2006; 17(2): 94-8.

137) Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang

WY, Chuang WL. A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b

plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan.

Liver Int. 2006; 26(1): 73-81.

138) Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O,

Noviello S, Brass C, Albrecht J. Efficacy of 24 weeks treatment with peginterferon alfa-2b

plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low

pretreatment viremia. J Hepatol. 2006; 44(1): 97-103.

139) Carr C, Hollinger FB, Yoffe B, Wakil A, Phillips J, Bzowej N, Leung J, Mirro K, Poordad F,

Moore DH, Gish RG. Efficacy of interferon alpha-2b induction therapy before retreatment for

chronic hepatitis C. Liver Int. 2007; 27(8): 1111-8.

140) Diago M, Crespo J, Olveira A, Pérez R, Bárcena R, Sánchez-Tapias JM, Muñoz-Sánchez M,

Romero-Gómez M. Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment

with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true

non-responder patients. Aliment Pharmacol Ther. 2007; 26(8): 1131-8.

141) Diago M, Olveira A, Solá R, Romero-Gómez M, Moreno-Otero R, Pérez R, Salmerón J,

Enríquez J, Planas R, Gavilán JC, Del Olmo J, Uribarrena R, Sillero C, Benítez A,

Sánchez-Galdón S, Dalmau B, Eraña L, Montoro M, Portu J, Garijo JM, Barniol R,

Domínguez A, Rota R, Olcoz JL, Antón M, Pamplona X, Casanovas T, Jiménez E, Huarte M,

Díaz F, Sánchez-Ruano J, Orive M, Muñoz-Sánchez M, Roset M. Treatment of chronic

hepatitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine

clinical practice in Spain: early prediction of sustained virological response rate. Aliment

Pharmacol Ther. 2007; 25(8): 899-906.

142) Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K,

77

Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M. Pegylated

interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of

rapid and early virologic response. Hepatology. 2007; 46(6): 1732-40.

143) Kuboki M, Iino S, Okuno T, Omata M, Kiyosawa K, Kumada H, Hayashi N, Sakai T.

Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic hepatitis C in

Japanese patients. J Gastroenterol Hepatol. 2007; 22(5): 645-52.

144) Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V,

Bengtsson L, McNair L, Alam J. Phase 2 study of the combination of merimepodib with

peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic

hepatitis C. J Hepatol. 2007; 47(4): 476-83.

145) Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and

ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology. 2007; 46(6):

1688-94.

146) Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, Luketic VA, Sanyal

AJ. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and

epoetin alpha. Hepatology. 2007; 46(2): 371-9.

147) Sjogren MH, Sjogren R Jr, Lyons MF, Ryan M, Santoro J, Smith C, Reddy KR, Bonkovsky H,

Huntley B, Faris-Young S. Antiviral response of HCV genotype 1 to consensus interferon and

ribavirin versus pegylated interferon and ribavirin. Dig Dis Sci. 2007; 52(6): 1540-7.

148) Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh

MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin

for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007; 56(4):

553-9.

149) Angelico M, Koehler-Horst B, Piccolo P, Angelico F, Gentile S, Francioso S, Tarquini P,

Vecchia RD, Ponti L, Pilleri G, Barlattani A, Grieco A, Soccorsi F, Guarascio P, Demelia L,

Sorbello O, Rossi Z, Forlini G, Zaru S, Bandiera F; SMIEC II Investigators. Peginterferon

alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological

responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin

and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve

patients with chronic hepatitis C. Eur J Gastroenterol Hepatol. 2008; 20(7): 680-7.

150) Bain VG, Lee SS, Peltekian K, Yoshida EM, Deschênes M, Sherman M, Bailey R,

Witt-Sullivan H, Balshaw R, Krajden M; Canadian PEGASYS Study Group. Clinical trial:

exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection

treated with peginterferon alpha-2a plus ribavirin. Aliment Pharmacol Ther. 2008; 28(1):

43-50.

151) Lagging M, Langeland N, Pedersen C, Färkkilä M, Buhl MR, Mørch K, Dhillon AP, Alsiö A,

78

Hellstrand K, Westin J, Norkrans G; NORDynamIC Study Group. Randomized comparison of

12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype

2/3 infection. Hepatology. 2008; 47(6): 1837-45.

152) Napoli N, Giannelli G, Antonaci A, Antonaci S. The use of different Peg-interferon alpha-2b

regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not

affect the achievement of sustained virological response. J Viral Hepat. 2008; 15(4): 300-4.

153) Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, Bellia V, Del Poggio P,

Fornaciari G, Ceriani R, Ramella G, Corradi C, Rossini A, Bruno S; Gruppo Epatologico

Lombardo. Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated

treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.

Antivir Ther. 2008; 13(5): 663-73.

154) Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G.

Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active

chronic hepatitis: a pilot study. J Interferon Cytokine Res. 2008; 28(10): 623-9.

155) Sood A, Midha V, Hissar S, Kumar M, Suneetha PV, Bansal M, Sood N, Sakhuja P, Sarin SK.

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon

in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian

experience. J Gastroenterol Hepatol. 2008; 23(2): 203-7.

156) Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, Naoumov NV. Clinical

trial: individualized treatment duration for hepatitis C virus genotype 1 with

peginterferon-alpha 2a plus ribavirin. Aliment Pharmacol Ther. 2008; 27(9): 810-9.

157) von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, Hinrichsen H,

Weidenbach H, Gerken G, Manns M, Buggisch P, Herrmann E, Zeuzem S. Placebo-controlled

trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in

chronic hepatitis C virus-1 infection. Hepatology. 2008; 48(5): 1404-11.

158) Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC,

Hsieh MY, Wang LY, Chang WY, Chuang WL. Rapid virological response and treatment

duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology. 2008;

47(6): 1884-93.

159) Zeuzem S, Yoshida EM, Benhamou Y, Pianko S, Bain VG, Shouval D, Flisiak R, Rehak V,

Grigorescu M, Kaita K, Cronin PW, Pulkstenis E, Subramanian GM, McHutchison JG.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with

genotype 1 chronic hepatitis C. Hepatology. 2008; 48(2): 407-17.

160) Andriulli A, Cursaro C, Cozzolongo R, Iacobellis A, Valvano MR, Mangia A, Minerva N,

Bacca D, Stanzione M, Scuteri A, Montalto G, Andreone P. Early discontinuation of ribavirin

in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin. J Viral

79

Hepat. 2009; 16(1): 28-35.

161) Bressler B, Wang K, Grippo JF, Heathcote EJ. Pharmacokinetics and response of obese

patients with chronic hepatitis C treated with different doses of PEG-IFN alpha-2a (40KD)

(PEGASYS). Br J Clin Pharmacol. 2009; 67(3): 280-7.

162) Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourlière M,

Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam

J, Pawlotsky JM, Zeuzem S; PROVE2 Study Team. Telaprevir and peginterferon with or

without ribavirin for chronic HCV infection. N Engl J Med. 2009; 360(18): 1839-50.

163) Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, Sata M. A randomized study of

extended treatment with peginterferon alpha-2b plus ribavirin based on time to HCV RNA

negative-status in patients with genotype 1b chronic hepatitis C. Am J Gastroenterol. 2009;

104(1): 70-5.

164) Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandão-Mello CE, Reddy

KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A. Re-treatment of

patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized

trial. Ann Intern Med. 2009; 150(8): 528-40.

165) Kawaoka T, Kawakami Y, Tsuji K, Ito H, Kitamoto M, Aimitsu S, Kawakami H, Jeong SC,

Imamura M, Aikata H, Takahashi S, Chayama K. Dose comparison study of pegylated

interferon-alpha-2b plus ribavirin in naïve Japanese patients with hepatitis C virus genotype 2:

a randomized clinical trial. J Gastroenterol Hepatol. 2009; 24(3): 366-71.

166) Langlet P, D'Heygere F, Henrion J, Adler M, Delwaide J, Van Vlierberghe H, Mulkay JP,

Lasser L, Brenard R, Horsmans Y, Michielsen P, Laureys A, Nevens F. Clinical trial: a

randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in

treatment-naïve or relapsing chronic hepatitis C patients. Aliment Pharmacol Ther. 2009;

30(4): 352-63.

167) McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee

WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K,

Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team.

Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J

Med. 2009; 361(6): 580-93.

168) Roberts SK, Weltman MD, Crawford DH, McCaughan GW, Sievert W, Cheng WS,

Rawlinson W, Desmond PV, Marks PS, Yoshihara M, Rizkalla B, Depamphilis JK, Dore GJ;

Chariot Study Group. Impact of high-dose peginterferon alfa-2A on virological response rates

in patients with hepatitis C genotype 1: a randomized controlled trial. Hepatology. 2009;

50(4): 1045-55.

169) Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB. Improved virologic response in chronic

80

hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin.


170) Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson

L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S,

McHutchison JG; MErimepodib TRiple cOmbination Study Group. Merimepodib, pegylated

interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin

nonresponders. Hepatology. 2009; 50(6): 1719-26.

171) Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, Atsumi H,

Nakano S, Arakawa T. Eight-week regimen of antiviral combination therapy with

peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus

genotype 2 and a rapid virological response. Liver Int. 2009; 29(1): 120-5.

172) Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP,

Marino-Marsilia G, Fontanella L, Leandro G. Peginterferon alfa-2a plus ribavirin is more

effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus

infection. Gastroenterology. 2010; 138(1): 116-22.

173) Brady DE, Torres DM, An JW, Ward JA, Lawitz E, Harrison SA. Induction pegylated

interferon alfa-2b in combination with ribavirin in patients with genotypes 1 and 4 chronic

hepatitis C: a prospective, randomized, multicenter, open-label study. Clin Gastroenterol

Hepatol. 2010; 8(1): 66-71.e1.

174) Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L. Pioglitazone

improves virological response to peginterferon alpha-2b/ribavirin combination therapy in

hepatitis C genotype 4 patients with insulin resistance. Liver Int. 2010; 30(3): 447-54.

175) Mecenate F, Pellicelli AM, Barbaro G, Romano M, Barlattani A, Mazzoni E, Bonaventura ME,

Nosotti L, Arcuri P, Picardi A, Barbarini G, D'Ambrosio C, Paffetti A, Andreoli A, Soccorsi F;

Club Epatologi Ospedalieri (CLEO) Group. Short versus standard treatment with pegylated

interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo

trial. BMC Gastroenterol. 2010; 10: 21.

176) Méndez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Morán S, Juarez JA,

Chung RT, Dehesa-Violante M. A randomized controlled trial of double versus triple therapy

with amantadine for genotype 1 chronic hepatitis C in Latino patients. Dig Dis Sci. 2010;

55(9): 2629-35.

177) Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E,

Russo A, Colombo M. Randomized study of peginterferon-alpha2a plus ribavirin vs

peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology. 2010; 138(1):

108-15.

178) , , , , , . C

81

. . 2011; 52(Suppl 1): A157.

179) Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K,

Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study

Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J

Med. 2004; 351(15): 1521-31.

180) Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai

CL. Long-term lamivudine therapy reduces the risk of long-term complications of chronic

hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007; 12(8):

1295-303.

181) Papatheodoridis GV, Dimou E, Dimakopoulos K, Manolakopoulos S, Rapti I, Kitis G,

Tzourmakliotis D, Manesis E, Hadziyannis SJ. Outcome of hepatitis B e antigen-negative

chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.

Hepatology. 2005; 42(1): 121-9.


Kawamura Y, Kobayashi M, Kumada H. Comparison of interferon and lamivudine treatment

in Japanese patients with HBeAg positive chronic hepatitis B. J Med Virol. 2007; 79(9):

1286-92.

183) Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks

I, Kane RL, Wilt TJ. Antiviral therapy for adults with chronic hepatitis B: a systematic review

for a National Institutes of Health Consensus Development Conference. Ann Intern Med.

2009; 150(2): 111-24.

184) Tramarin A, Gennaro N, Compostella FA, Gallo C, Wendelaar Bonga LJ, Postma MJ. HCV

screening to enable early treatment of hepatitis C: a mathematical model to analyse costs and

outcomes in two populations. Curr Pharm Des. 2008; 14(17): 1655-60.

185) Nakamura J, Terajima K, Aoyagi Y, Akazawa K. Cost-effectiveness of the national screening

program for hepatitis C virus in the general population and the high-risk groups. Tohoku J

Exp Med. 2008; 215(1): 33-42.

186) Loubière S, Rotily M, Moatti JP. Prevention could be less cost-effective than cure: the case of

hepatitis C screening policies in France. Int J Technol Assess Health Care. 2003; 19(4):

632-45.

187) Singer ME, Younossi ZM. Cost effectiveness of screening for hepatitis C virus in

asymptomatic, average-risk adults. Am J Med. 2001; 111(8): 614-21.

188) . . . 1999;

46(6): 447-65.

189) Jusot JF, Colin C. Cost-effectiveness analysis of strategies for hepatitis C screening in French

82

blood recipients. Eur J Public Health. 2001; 11(4): 373-9.

190) Saab S, Brezina M, Gitnick G, Martin P, Yee HF Jr. Hepatitis C screening strategies in

hemodialysis patients. Am J Kidney Dis. 2001; 38(1): 91-7.

191) Leal P, Stein K, Rosenberg W. What is the cost utility of screening for hepatitis C virus (HCV)

in intravenous drug users? J Med Screen. 1999; 6(3): 124-31.

192) Veldhuijzen IK, Toy M, Hahné SJ, De Wit GA, Schalm SW, de Man RA, Richardus JH.

Screening and early treatment of migrants for chronic hepatitis B virus infection is

cost-effective. Gastroenterology. 2010; 138(2): 522-30.

193) Kang JY, Lee TP, Yap I, Lun KC. Analysis of cost-effectiveness of different strategies for

hepatocellular carcinoma screening in hepatitis B virus carriers. J Gastroenterol Hepatol.

1992; 7(5): 463-8.

194) Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, Jackson S, Ryder

S, Price A, Stein K. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review

and economic analysis. Health Technol Assess. 2007; 11(34): 1-206.

195) Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U. Cost-effectiveness of hepatocellular

carcinoma surveillance in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol

Hepatol. 2005; 3(1):75-84.

196) Nakamura J, Toyabe SI, Aoyagi Y, Akazawa K. Economic impact of extended treatment with

peginterferon alpha-2a and ribavirin for slow hepatitis C virologic responders. J Viral Hepat.

2008; 15(4): 293-9.

197) Nakamura J, Kobayashi K, Toyabe S, Aoyagi Y, Akazawa K. The cost-effectiveness of the

new protocol reflecting rapid virologic response to peginterferon alpha-2b and ribavirin for

chronic hepatitis C. Eur J Gastroenterol Hepatol. 2007; 19(9): 733-9.

198) Hayashida K, Nagasue I, Fukuda T, Gunji A. The natural history model of hepatitis C virus

infection and the economic evaluation of alpha interferon treatment. J Epidemiol. 2002; 12(1):

22-32.

199) Ishida H, Wong JB, Hino K, Kurokawa F, Nishina S, Sakaida I, Okita K, Tamesa T, Oka M,

Torimura T, Sata M, Takahashi S, Chayama K, Inoue Y. Validating a Markov model of

treatment for hepatitis C virus-related hepatocellular carcinoma. Methods Inf Med. 2008;

47(6): 529-40.

200) Zauber AG, Vogelaar IL, Knudsen AB, Wilschut J, van Ballegooijen M, Kuntz KM.

Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S.

Preventive Services Task Force. Ann Intern Med. 2008; 149(9): 659-69.

201) Mandelblatt JS, Cronin KA, Bailey S, Berry DA, de Koning HJ, Draisma G, Huang H, Lee SJ,

Munsell M, Plevritis SK, Ravdin P, Schechter CB, Sigal B, Stoto MA, Stout NK, van

Ravesteyn NT, Venier J, Zelen M, Feuer EJ; Breast Cancer Working Group of the Cancer

83

Intervention and Surveillance Modeling Network (CISNET). Effects of Mammography

Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and

Harms. Ann Intern Med. 2009; 151(10): 738-47.

202) Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L; Trial Management Group.

Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’

follow-up: a randomized controlled trial. Lancet. 2006; 368(9552): 2053-60.

203) U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy:

U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern

Med. 2009; 150(12): 869-73, W154.

204) Lin K, Vickery J. Screening for hepatitis B virus infection in pregnant women: evidence for

the U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern

Med. 2009; 150(12): 874-6.

205) U.S. Preventive Services Task Force. Screening for Hepatitis B Virus Infection: A Brief

Evidence Update for the U.S. Preventive Services Task Force. AHRQ Pub. No. 05-0552-B.

February 2004.

206) U.S. Preventive Services Task Force. Screening for Hepatitis B Virus Infection:

Recommendation Statement. AHRQ Pub. No. 05-0552-A. 3 February 2004.

207) U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults:

recommendation statement. Ann Intern Med. 2004; 140(6): 462-4.

208) Chou R, Clark EC, Helfand M; U.S. Preventive Services Task Force. Screening for hepatitis C

virus infection: a review of the evidence for the U.S. Preventive Services Task Force. Ann

Intern Med. 2004; 140(6): 465-79.

209) Hill L, Henry B, Schweikert S; Prevention Practice Committee, American College of

Preventive Medicine. Screening for chronic hepatitis C: American College of Preventive

Medicine practice policy statement. Am J Prev Med. 2005; 28(3): 327-30.

210) NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci

Statements. 2002 Jun 10-12; 19(3): 1-46.

211) VA National Clinical Public Health Programs. Hepatitis C Topics: Hepatitis C Testing and

Prevention Counseling Guidelines for VA Health Care Practitioners.

(http://www.hepatitis.va.gov/vahep?page=prtop05-gd-01&pf=doc-pf&pp=pf)

212) CDC(Centers for Disease Control and Prevention). National Hepatitis C Prevention Strategy.

2001.

213) WHO/Europe Health Evidence Network (HEN) synthesis report. What is the evidence for the

effectiveness of interventions to reduce hepatitis C infection and the associated morbidity?

2005.

214) Yoo KY. Cancer control activities in the Republic of Korea. Jpn J Clin Oncol. 2008; 38(5):

84

327-33.

215) Evidence Report /Technology Assessment, Number 60. Management of Chronic Hepatitis C.

AHRQ Pub. No. 02-E030. July 2002.

216) National Cancer Institute. Liver (Hepatocellular) Cancer Screening (PDQ®). Health

Professional Version.

(http://www.cancer.gov/cancertopics/pdq/screening/hepatocellular/healthprofessional/allpages

/print)

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3 (MEDLINE 1985/01/01 )

CQ AFCQ CQ

CQCQ

1 0 0 1HBV 3HCV 2

HBV&HCV 20

PubMedA 2 HCV-2 HCV2009/6/17

(("hepatitis c"[MeSH Terms] OR "hepatitis c"[All Fields] OR "hepacivirus"[MeSH Terms] OR"hepacivirus"[All Fields]) AND ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[AllFields] OR "mass screening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR"mass screening"[All Fields] OR "screening"[All Fields] OR "early detection of cancer"[MeSH Terms]OR ("early"[All Fields] AND "detection"[All Fields] AND "cancer"[All Fields]) OR "early detection ofcancer"[All Fields]) AND ("carcinoma, hepatocellular"[MeSH Terms] OR ("carcinoma"[All Fields] AND"hepatocellular"[All Fields]) OR "hepatocellular carcinoma"[All Fields] OR ("hepatocellular"[All Fields]AND "carcinoma"[All Fields]))) AND (("1985"[PDAT] : "2009"[PDAT]) AND "humans"[MeSH Terms]AND (English[lang] OR Japanese[lang]))

1,894 0 HBV 0HCV 0

CQ1:5CQ3:1CQ4:2CQ7:4

CQ7&8:1

PubMedb 2 HBV-2

HCV-2

HBV

HCV2010/2/26

"mass screening"[MeSH Terms] OR "early detection of cancer"[MeSH Terms] AND "liverneoplasms"[MeSH Terms] AND ("mortality"[Subheading] OR "mortality"[All Fields] OR"mortality"[MeSH Terms]) AND ("randomized controlled trial"[Publication Type] OR "randomizedcontrolled trials as topic"[MeSH Terms] OR "randomized controlled trial"[All Fields] OR "randomisedcontrolled trial"[All Fields]) NOT ("review"[Publication Type] OR "review literature as topic"[MeSHTerms] OR "review"[All Fields])

5 0 0 0

PubMeda 2 US-2 2010/2/26

(("ultrasonography"[Subheading] OR "ultrasonography"[All Fields] OR "ultrasonography"[MeSH Terms])AND ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "massscreening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[AllFields] OR "screening"[All Fields] OR "early detection of cancer"[MeSH Terms] OR ("early"[All Fields]AND "detection"[All Fields] AND "cancer"[All Fields]) OR "early detection of cancer"[All Fields]) AND("carcinoma"[MeSH Terms] OR "carcinoma"[All Fields]) AND ("randomized controlledtrial"[Publication Type] OR "randomized controlled trials as topic"[MeSH Terms] OR "randomizedcontrolled trial"[All Fields] OR "randomised controlled trial"[All Fields])) AND ("humans"[MeSHTerms] AND (English[lang] OR Japanese[lang]) AND ("1985"[PDAT] : "3000"[PDAT]))

75 0 0 0

PubMeda 3 US-2 2010/2/26

(("ultrasonography"[Subheading] OR "ultrasonography"[All Fields] OR "ultrasonography"[MeSH Terms])AND ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "massscreening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[AllFields] OR "screening"[All Fields] OR "early detection of cancer"[MeSH Terms] OR ("early"[All Fields]AND "detection"[All Fields] AND "cancer"[All Fields]) OR "early detection of cancer"[All Fields]) AND("carcinoma"[MeSH Terms] OR "carcinoma"[All Fields]) AND ("randomized controlledtrial"[Publication Type] OR "randomized controlled trials as topic"[MeSH Terms] OR "randomizedcontrolled trial"[All Fields] OR "randomised controlled trial"[All Fields])) AND ("humans"[MeSHTerms] AND (English[lang] OR Japanese[lang]) AND ("1985"[PDAT] : "3000"[PDAT]))

75 1 1 5 CQ4:1CQ7:1

PubMedHB 4 HBV-4 B 2010/1/6

("1985/1/1"[PDAT] : "3000"[PDAT]) AND (("hepatitis"[MeSH Terms] OR "hepatitis"[All Fields]) ANDHbs[All Fields] AND ("antigens"[MeSH Terms] OR "antigens"[All Fields] OR "antigen"[All Fields])AND ("sensitivity and specificity"[MeSH Terms] OR ("sensitivity"[All Fields] AND "specificity"[AllFields]) OR "sensitivity and specificity"[All Fields] OR "sensitivity"[All Fields]) AND ("sensitivity andspecificity"[MeSH Terms] OR ("sensitivity"[All Fields] AND "specificity"[All Fields]) OR "sensitivityand specificity"[All Fields] )

109 4 0 HBV 5 0

PubMedHC 4 HCV-4 C 2010/1/6

("1985/1/1"[PDAT] : "3000"[PDAT]) AND ((("hepatitis"[MeSH Terms]) AND HCV[All Fields] AND("immunoglobulins"[MeSH Terms] OR "antibodies"[MeSH Terms]) AND ("sensitivity andspecificity"[MeSH Terms]) AND ("humans"[MeSH Terms] AND (English[lang] OR Japanese[lang])))

353 1 0 HBV&HCV 1 0

PubMedc 4 US-2 2010/2/26

"ultrasonography"[MeSH Terms] AND ("mass screening"[MeSH Terms] OR "early detection ofcancer"[MeSH Terms]) AND ("liver neoplasms"[MeSH Terms] AND "cancer"[All Fields]) OR "livercancer"[All Fields] AND "sensitivity and specificity"[MeSH Terms] AND "sensitivity andspecificity"[MeSH Terms] AND ("humans"[MeSH Terms] AND (English[lang] OR Japanese[lang])AND ("1985"[PDAT] : "3000"[PDAT])) NOT ("review"[Publication Type] OR "review literature astopic"[MeSH Terms] OR "review"[All Fields])

139 0 0 3 0

PubMedd 4 US-2 2010/2/26

(("ultrasonography"[Subheading] OR "ultrasonography"[All Fields] OR "ultrasonography"[MeSH Terms])AND ("diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "screening"[All Fields] OR "massscreening"[MeSH Terms] OR ("mass"[All Fields] AND "screening"[All Fields]) OR "mass screening"[AllFields] OR "screening"[All Fields] OR "early detection of cancer"[MeSH Terms] OR ("early"[All Fields]AND "detection"[All Fields] AND "cancer"[All Fields]) OR "early detection of cancer"[All Fields]) AND("liver neoplasms"[MeSH Terms] OR ("liver"[All Fields] AND "neoplasms"[All Fields]) OR "liverneoplasms"[All Fields] OR ("liver"[All Fields] AND "cancer"[All Fields]) OR "liver cancer"[All Fields])AND adverse[All Fields] AND effect[All Fields]) AND ("humans"[MeSH Terms] AND (English[lang]OR Japanese[lang]) AND ("1985"[PDAT] : "3000"[PDAT])) NOT ("review"[Publication Type] OR"review literature as topic"[MeSH Terms] OR "review"[All Fields])

25 0 0 0 0

5 US-6 2010/12/28"ultrasonography"[MeSH Terms] OR "ultrasonography"[All Fields] OR "ultrasonic"[All Fields] OR"ultrasonics"[MeSH Terms] OR "ultrasonics"[All Fields]) AND gel[All Fields] AND ("dermatitis"[MeSHTerms] OR "dermatitis"[All Fields])

11 0 1 1 0

PubMed

adverse effect6 HBV-6

HCV-6BC

2010/1/6("1985"[PDAT] : "3000"[PDAT]) AND (("liver"[MeSH Terms] OR "liver"[All Fields]) AND "biopsy,needle/adverse effects"[All Fields]) AND ("humans"[MeSH Terms] AND (English[lang] ORJapanese[lang])) NOT "review literature as topic"[MeSH Terms]

295 12 0 12 0

PubMedB 7 HBV-7HCV-7

BC

2009/9/14

"interferons"[MeSH Terms] AND "hepatitis"[MeSH Terms] AND "liver neoplasms"[MeSH Terms]AND (("1985"[PDAT] : "3000"[PDAT]) AND "humans"[MeSH Terms] AND (English[lang] ORJapanese[lang])) AND (("1985"[PDAT] : "2009"[PDAT]) AND "humans"[MeSH Terms] AND(English[lang] OR Japanese[lang])) NOT ("review"[Publication Type] OR "review literature astopic"[MeSH Terms] OR "review"[All Fields])

322 15 1HBV 3HCV 19

HBV&HCV 2

CQ1:1CQ9:1

PubMedC 8 HBV-9HCV-8

BC

2009/10/28

(("interferons"[MeSH Terms] OR "interferons"[All Fields] OR "interferon"[All Fields]) AND("hepatitis"[MeSH Terms] OR "hepatitis"[All Fields]) AND adverse[All Fields] AND effect[All Fields])AND (("1985"[PDAT] : "2009/10"[PDAT]) AND "humans"[MeSH Terms] AND (English[lang] ORJapanese[lang])) NOT ("review"[Publication Type] OR "review literature as topic"[MeSH Terms] OR"review"[All Fields])

341 5 1 7 0

8 HBV-9HCV-8

BC

(("interferons"[majr]) AND ("Hepatitis C, Chronic"[Majr]) AND("randomized controlled trial"[pt]))AND (pegylated[tiab] OR"peg"[tiab] OR "peginterferon"[tiab] OR "pegasys"[tiab] OR"pegintron"[tiab])AND English[lang] OR Japanese[lang])

212 68 0 68 0

PubMedlamivudine 9/10 HBV-8 B 2009/12/7

("1985/01/01"[PDAT] : "3000"[PDAT]) AND ("hepatitis b"[MeSH Terms] AND "lamivudine"[MeSHTerms] AND "carcinoma, hepatocellular"[MeSH Terms]) AND ("humans"[MeSH Terms] AND(English[lang] OR Japanese[lang])) NOT "review literature as topic"[MeSH Terms]

66 4 0 0

PubMedentecavir 9/10 HBV-8 B 2009/12/7

("1985/01/01"[PDAT] : "3000"[PDAT]) AND ("hepatitis b"[MeSH Terms] AND ("entecavir"[SubstanceName] OR "entecavir"[All Fields])) AND "carcinoma, hepatocellular"[MeSH Terms] AND("humans"[MeSH Terms] AND (English[lang] OR Japanese[lang])) NOT "review literature astopic"[MeSH Terms]

12 1 0 0

PubMedadefovir 9/10 HBV-8 B 2009/12/7

("1985/01/01"[PDAT] : "3000"[PDAT]) AND ("hepatitis b"[MeSH Terms] AND ("adefovir"[SubstanceName] OR "adefovir"[All Fields]) AND "carcinoma, hepatocellular"[MeSH Terms]) AND("humans"[MeSH Terms] AND (English[lang] OR Japanese[lang])) NOT "review literature astopic"[MeSH Terms]

26 0 0 0

129 3,960 111 5 138 17

0

CQ9:2CQ9&10:3

102

CQ

J Dream II 2010/2/12 ++

[ ] AND AND AND

[ / ]From: 1985 AND [ ] OR

106 CQ3:1

2010/2/12 ++

( /TH or /AL) and ( /TH or /AL) and ( /TH or

/AL) AND (DT=1985:2010)

322 CQ4:1

2010/12/28

( /TH or /AL) and ( /TH or /AL) and ( /TH or /AL)

5 CQ5:1

190 CQ3:1

623 4

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103

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CQ

No.

CQ

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4

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g B

H,

et a

l.20

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FP6

: 9,3

73: 9

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HB

35~5

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2.6%

: 63.

3%

5(

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1.37

(95%

CI:

0.99

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89)

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(95%

CI:

0.41

-0.

98)

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hen

TH,

et a

l.20

02U

S(

)

:4,

385

:45

8

1: H

B/H

CA

FP/

/

50:

45.0

%:

43.3

%

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:59

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70.

76(9

5%C

I: 0.

38-

1.52

)

55B

olon

di L

, et

al.

2001

US+

AFP

6

: 61

( 3

13)

: 104

: :

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61.7

%

56(6

~100

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): 4

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56,

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90

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(

)

: 45

( 8

78)

: 454

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:

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~70

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)

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2(2

): 8

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: 31.

7%

57,

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08

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69: 1

64

: :,

(,

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66.8

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15 ()

; 5, 1

0,

15

:36

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, 9.1

%, 4

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:18

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, 7.3

%, 4

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:38

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, 9.2

%, 4

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105

7

No ( ) ( ) (%) (%) (%)

69

Rivera-Sanfeliz G, Kinney TB, Rose SC, Agha AK, Valji K, Miller FJ, Roberts AC.

Single-pass percutaneous liver biopsy for diffuse liver disease using an automated device: experience in 154 procedures.

2005 153 - 18.2 -

70Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A.

Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London.

1995 1,500 0.33 - 1.7

71 Piccinino F, Sagnelli E, Pasquale G, Giusti G.

Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies.

1986 68,276 0.009 - 0.32

72 Myers RP, Fong A, Shaheen AA.

Utilization rates, complications and costs of percutaneous liver biopsy: a population-based study including 4275 biopsies.

2008 3,627 0.14 0.51 0.35

73Vivas S, Palacio MA, Rodríguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L.

Ambulatory liver biopsy: complications and evolution in 264 cases. 1998 378 - 16.6 -

74Sugano S, Sumino Y, Hatori T, Mizugami H, Kawafune T, Abei T.

Incidence of ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy.

1991 120 - - -

75

Caturelli E, Giacobbe A, Facciorusso D, Bisceglia M, Villani MR, Siena DA, Fusilli S, Squillante MM, Andriulli A.

Percutaneous biopsy in diffuse liver disease: increasing diagnostic yield and decreasing complication rate by routine ultrasound assessment of puncture site.

1996 753 - 3.5 -

76 Froehlich F, Lamy O, Fried M, Gonvers JJ.

Practice and complications of liver biopsy. Results of a nationwide survey in Switzerland.

1993 3,501 0.08 - 0.14

77van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU.

Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital.

2006 1,398 0.25 - 0.83

78

Lindor KD, Bru C, Jorgensen RA, Rakela J, Bordas JM, Gross JB, Rodes J, McGill DB, Reading CC, James EM, Charboneau JW, Ludwig J, Batts KP, Zinsmeister AR.

The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy.

1996 836 - 44 -

79

Montalto G, Soresi M, Carroccio A, Bascone F, Tripi S, Aragona F, Di Gaetano G, Notarbartolo A.

Percutaneous liver biopsy: a safe outpatient procedure? 2001 1,581 0.06 16.3 -

80 Chuah SY, Moody GA, Wicks AC, Mayberry JF.

A nationwide survey of liver biopsy--is there a need to increase resources, manpower and training?

1994 364 0.05 - -

CQ6. (HBV HCV )

106

8(B

)

C

Q7.

No

()

()

81C

amm

à C

, et

al.

2001

--

7(1

,505

122

)-

IFN

RD

: 6.

4%(9

5%C

I: 2.

8-10

)

82Su

ng JJ

, et a

l.20

08-

-2,

742

(12

)-

RR

: 0.6

6(95

%C

I: 0.

48-0

.89)

83M

iyak

e Y

, et

al.

2009

--

1,30

3(2

RC

T6

RC

T)-

IFN

RD

: 5.

0%(9

5%C

I: 9.

4-0.

5)

84Li

n SM

, et a

l.19

99: 6

7: 3

41.

1-11

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43)

: 1/6

7: 4

/34

85

Inte

rnat

iona

l

Hep

atoc

ellu

lar

Car

cino

ma

Stud

y G

roup

.

1998

(B

and/

or C

)63

7(

: 281

,: 2

59)

3R

R: 1

.99(

95%

CI:

1.09

-3.6

4):2

9/2

81: 6

6/3

56

107

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No

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mà

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t al

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3,10

9(3R

CT

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CT)

IFN

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vera

ll R

D:

12.8

%(9

5%C

I: 8.

3-17

.2)

85

Inte

rnat

iona

l

Hep

atoc

ellu

lar C

arci

nom

a St

udy

Gro

up.

1998

637

(28

1/

356

)IF

N3

: 18.

5%(6

6/35

6): 1

0.3%

(29/

281)

RR

: 1.9

9(95

%C

I: 1.

09-3

.64)

86N

ishi

guch

i S,

et a

l.19

9590

(45

/45

)2~

7: 2

(4%

): 1

7(3

8%)

(P=0

.002

)

87A

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oli F

, et

al.

2004

HC

(55

. 1±1

.4)

60(

30/

30)

2b+R

BV

5: 2

6%,

: 3%

(P<0

.01)

88B

enve

gnù

L,

et a

l.19

9818

9(

88/

101

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NIF

N71

.5±2

3.6

: 26.

7%,

: 5.6

%(P

<0.0

01)

89Y

oshi

da H

, et

al.

1999

C(F

4)23

0/

107

IFN

IFN

4.3

: 27.

0%(2

9/10

7): 1

4.3%

(33/

230)

(P=0

.057

3)

90V

alla

DC

, et

al.

1999

99(

47/

52)

IFN

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300 3

24)

IFN

472

: 17.

3%(9

/52)

: 10.

6%(5

/47)

108

No

()

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91M

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lla G

, et

al.

1996

HB

VH

CV Chi

ld-P

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A

193

/92

IFN

1984

~199

4

HB

V:

49 HC

V:

32

: 4.7

%(9

/193

): 5

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(5/9

2)

92Ik

eda

K, e

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2006

C2,

166

(1,

654

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2)

IFN

IFN

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(:

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12.7

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93Sh

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ri Y

, et

al.

2005

C34

5(

271

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8: 4

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(35/

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: 31.

0%(8

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95%

CI:

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7)

94Y

u M

L, e

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2006

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IFN

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: 12.

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013)

95Ik

eda

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2009

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454

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ram

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): 8

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573)

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ga K

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103

/30

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: 23.

3%(7

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: 4.9

%(5

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eda

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t al.

1999

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1,19

1/

452

)IF

NIF

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5:

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/4.

8%10

:7.

6%/

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%

109

10(C

)

C

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No

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()

81(

)

Cam

mà

C, e

t al.

2001

-3,

798

(3)

IFN

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ll R

D:

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(95%

CI:

2.3-

5.0)

89Y

oshi

daH

, et a

l.19

99C

(F0/

F1/F

2/F3

)

F0/F

1:71

0/

160

F2:

896

/16

4F3

:56

4/

59

IFN

IFN

4.3

F0/F

1:

1.9%

(3/1

60),

0.3%

(2/7

10)(

P>0.

2)F2

: 5.

5%(9

/164

), 1.

7%(1

5/89

6)(P

=0.0

128)

F3:

22.0

%(1

3/59

), 6.

7%(3

8/56

4)(P

=0.0

011)

98Ik

eda

K,

et a

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991,

643

(:

1,19

1/

:45

2)

IFN

IFN

5

5:

2.1%

, 4.

8%10

:7.

6%,

12.4

%

99In

oue

A,

et a

l.20

00: 2

24 : 699

IFN

IFN

54.9 70

.4

9.5%

(95%

CI:

7.1-

11.9

)2.

2%(9

5%C

I: 0.

0-4.

4)(P

=0.0

015)

110

11

73.4% 95.5%

69.3% 93.4%

62.8% 88.6%

38.2% 75.6%

22.1% 68.4%

43.2% 81.9%

31.7% 51.8%

31.2% -

24.1% 54.8%

29.6% -

36.7% -

( ) 30.2% 66.0%

60.3% 52.7%

46.2% 68.7%

40.7% 53.3%

26.1% -

36.7% -

27.1% -

23.6% -

92.5% 95.8%

65.8% 96.7%

89.4% 87.3%

84.9% 85.5%

82.9% 79.8%

81.4% 78.6%

- 70.8%

73.4% -

111

MEDLINE 2010/7/10

((cost benefit) or (cost utility) or (cost effective) or (cost effectiveness)) and ((hepatocellular carcinoma) or (liver cancer) or hepatitis or cirrhosis) and (model or models) and virus and ((IFN or interferon) or (screening or (secondary prevention) or (primary prevention) or surveillance))

169

(

)HIV

()

()

16

12

1

115

1

CQ No No Author Title Secondary Title Volume Number Pages Year

1 46 PMA1513

Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H.

Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients.

J Hepatol 28 6 930-8 1998

1 47 PMA1044

Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ; Taiwan Community-Based Cancer Screening Project Group.

Hepatitis B e antigen and the risk of hepatocellular carcinoma.

N Engl J Med 347 3 168-

74 2002

1 48 PMB103

Ikeda K, Arase Y, Kobayashi M, Someya T, Hosaka T, Saitoh S, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Kumada H.

Hepatitis B virus-related hepatocellular carcinogenesis and its prevention.

Inter-virology 48 1 29-38 2005

1 49Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group.

Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.

JAMA 295 1 65-73 2006

1 50 PMA43Ishiguro S, Inoue M, Tanaka Y, Mizokami M, Iwasaki M, Tsugane S; JPHC Study Group.

Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based cohort study in Japan.

Eur J Cancer Prev

18 1 26-32 2009

1 51 PMA1453 Pagliaro L, Peri V, Linea C, Cammà C, Giunta M, Magrin S. Natural history of chronic hepatitis C.

Ital JGastro-enterolHepatol

31 1 28-44 1999

1 52 PMA448Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, Morabito A, Colombo M.

The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients.

Hepatology 43 6 1303-

10 2006

3 53 a-34 Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma.

J Cancer Res Clin Oncol

130 7 417-22 2004

3 54 PMA1104Chen TH, Chen CJ, Yen MF, Lu SN, Sun CA, Huang GT, Yang PM, Lee HS, Duffy SW.

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan.

Int J Cancer 98 2 257-

61 2002

3 55Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L, Zanetti M, Sherman M.

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

Gut 48 2 251-9 2001

3 56 JD0212-98, , ,

, , ,, . .

88 63-70 1990

3 57 1, , ,

, , ,, , , .

. 46 1 35-45 2008

116


4 58 HB66

Palmer DR, Perry KR, Mortimer PP, Parry JV.

Variation in the sensitivity of HBsAg screening kits.

Transfus Med 6 4 311-7 1996

4 59 HB19 Motte A, Colson P, Tamalet C.

Evaluation of the clinical performance of the Beckman Coulter Access AbHBsII immunoassay for the detection of hepatitis B surface antibodies.

J Clin Virol 37 3 213-7 2006

4 60 HB99

Shih LN, Sheu JC, Wang JT, Huang GT, Yang PM, Lee HS, Sung JL, Wang TH, Chen DS.

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction.

J Med Virol 32 4 257-

60 1990

4 61 HB69 Gomes SA, Yoshida CF, Niel C.

Detection of hepatitis B virus DNA in hepatitis B surface antigen-negative serum by polymerase chain reaction: evaluation of different primer pairs and conditions.

Acta Virol 40 3 133-8 1996

4 62 PMA134

Togashi H, Hashimoto C, Yokozawa J, Suzuki A, Sugahara K, Saito T, Yamaguchi I, Badawi H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S.

What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?

J Hepatol 49 1 17-24 2008

4 63 HC152

Colin C, Lanoir D, Touzet S, Meyaud-Kraemer L, Bailly F, Trepo C; HEPATITIS Group.

Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an analysis of the literature.

J Viral Hepat 8 2 87-95 2001

4 64 a-41 Sherman M, Peltekian KM, Lee C.

Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population.

Hepatology 22 2 432-8 1995

4 65 PMA1205 Tong MJ, Blatt LM, Kao VW.

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.

Ital JGastro-enterolHepatol

16 5 553-9 2001

4 66

Ichu0212-216

59

, , ,, . . 33 2 169-

173 1995

5 67 , , ,, , . 1 . 71 2 128-

30 2009

117


5 68 Erdmann SM, Sachs B, Merk HF.Allergic contact dermatitis due to methyldibromo glutaronitrile in Euxyl K 400 in an ultrasonic gel.

Contact Dermatitis 44 1 39-40 2001

6 69 adverse effect58



Cardiovasc Intervent Radiol

28 5 584-8 2005


Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A.


Gut 36 3 437-41 1995


Piccinino F, Sagnelli E, Pasquale G, Giusti G.


J Hepatol 2 2 165-73 1986


Myers RP, Fong A, Shaheen AA.


Liver Int 28 5 705-12 2008


Vivas S, Palacio MA, Rodríguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L.

Ambulatory liver biopsy: complications and evolution in 264 cases.

Rev Esp Enferm Dig

90 3 175-82 1998


Sugano S, Sumino Y, Hatori T, Mizugami H, Kawafune T, Abei T.


Dig Dis Sci 36 9 1229-

33 1991




Am J Gastro-enterol

91 7 1318-21 1996


Froehlich F, Lamy O, Fried M, Gonvers JJ.



4 1993


van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU.


Intern Med J 36 11 692-9 2006

118



Lindor KD, Bru C, Jorgensen RA, Rakela J, Bordas JM, Gross JB, Rodes J, McGill DB, Reading CC, James EM, Charboneau JW, Ludwig J, Batts KP, Zinsmeister AR.



83 1996



Percutaneous liver biopsy: a safe outpatient procedure? Digestion 63 1 55-60 2001


Chuah SY, Moody GA, Wicks AC, Mayberry JF.

A nationwide survey of liver biopsy - Is there a need to increase resources, manpower and training?

Hepato-gastro-enterology

41 1 4-8 1994

7 81 PMB198 Cammà C, Giunta M, Andreone P, Craxì A.

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.

J Hepatol 34 4 593-602 2001

7 82 PMB18 Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL.

Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma.

Aliment Pharmacol Ther

28 9 1067-77 2008

7 83 PMB4 Miyake Y, Kobashi H, Yamamoto K.

Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection.

J Gastro-enterol 44 5 470-5 2009

7 84 PMB252 Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF.

Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.

Hepatology 29 3 971-5 1999

7 85 PMB246International Interferon-alpha Hepatocellular Carcinoma Study Group.

Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.

Lancet 351 9115 1535-9 1998

7 86 PMA1674

Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S.

Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.

Lancet 346 8982 1051-5 1995

7 87 a-30

Azzaroli F, Accogli E, Nigro G, Trere D, Giovanelli S, Miracolo A, Lodato F, Montagnani M, Tamé M, Colecchia A, Mwangemi C, Festi D, Roda E, Derenzini M, Mazzella G.

Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study on patients with HCV related cirrhosis.

World JGastro-enterol

10 21 3099-102 2004

119


7 88 PMB257 Benvegnù L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A.

Retrospective analysis of the effect of interferon therapy on the clinical outcome of patients with viral cirrhosis.

Cancer 83 5 901-9 1998

7 89 PMA1423

Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M.

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

Ann Intern Med 131 3 174-

81 1999

7 90 PMB245

Valla DC, Chevallier M, Marcellin P, Payen JL, Trepo C, Fonck M, Bourliere M, Boucher E, Miguet JP, Parlier D, Lemonnier C, Opolon P.

Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.


5 1999

7 91 PMB290

Mazzella G, Accogli E, Sottili S, Festi D, Orsini M, Salzetta A, Novelli V, Cipolla A, Fabbri C, Pezzoli A, Roda E.

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.

J Hepatol 24 2 141-7 1996

7 92 PMB81

Ikeda K, Arase Y, Saitoh S, Kobayashi M, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Kumada H.

Anticarcinogenic impact of interferon on patients with chronic hepatitis C: a large-scale long-term study in a single center.

Inter-virology 49 1-2 82-90 2006

7 93 PMA682

Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E, Hirota K, Yoshida H, Ohashi Y, Omata M; Tokyo-Chiba Hepatitis Research Group.

Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival.


14 2005

7 94 PMB53Yu ML, Lin SM, Chuang WL, Dai CY, Wang JH, Lu SN, Sheen IS, Chang WY, Lee CM, Liaw YF.

A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan.

Antivir Ther 11 8 985-

94 2006

7 95 PMB3

Ikeda K, Arase Y, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Kumada H.

Necessities of interferon therapy in elderly patients with chronic hepatitis C.

Am J Med 122 5 479-86 2009

7 96 PMB200

Gramenzi A, Andreone P, Fiorino S, Cammà C, Giunta M, Magalotti D, Cursaro C, Calabrese C, Arienti V, Rossi C, Di Febo G, Zoli M, Craxì A, Gasbarrini G, Bernardi M.

Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis.

Gut 48 6 843-8 2001

7 97 PMB90 Soga K, Shibasaki K, Aoyagi Y.Effect of interferon on incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Hepato-gastro-enterology

52 64 1154-8 2005

120


7 98 PMB251

Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Nakamura I, Murashima N, Kumada H, Kawanishi M.

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.


30 1999

7 99Inoue A, Tsukuma H, Oshima A, Yabuuchi T, Nakao M, Matsunaga T, Kojima J, Tanaka S.

Effectiveness of interferon therapy for reducing the incidence of hepatocellular carcinoma among patients with type C chronic hepatitis.

JEpidemiol 10 4 234-

40 2000

7 100 PMA49

Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL; HALT-C Trial Investigators.

Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.

N Engl J Med 359 23 2429-

41 2008

7 101 PMA809

Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E, Hino K, Hayashi K, Tamura S, Itoh Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N.

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.

J Viral Hepat 11 2 148-

56 2004

7 102 PMA4

Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A, Silini EM, Almasio PL, Maisonneuve P.

Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study.

Am JGastro-enterol

104 5 1147-58 2009

8 103 PMA343

Fartoux L, Degos F, Trépo C, Goria O, Calès P, Tran A, Buffet C, Poynard T, Capron D, Raabe JJ, Roulot D, Naveau S, Grange JD, Poupon RE, Poupon R, Serfaty L.

Effect of prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a randomized trial.

ClinGastro-enterolHepatol

5 4 502-7 2007

8 104 PMB43

Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, Hosaka T, Sezaki H, Yatsuji H, Kawamura Y, Kobayashi M, Kumada H.

Prolonged-interferon therapy reduces hepatocarcinogenesis in aged-patients with chronic hepatitis C.


102 2007

8 105 PMC170 Koskinas J, Merkouraki P, Manesis E, Hadziyannis S.

Assessment of depression in patients with chronic hepatitis: effect of interferon treatment.

Dig Dis 20 3-4 284-8 2002

8 106 PMC295 Kanda Y, Shigeno K, Matsuo H, Yano M, Yamada N, Kumagami H. Interferon-induced sudden hearing loss. Audiology 34 2 98-

102 1995

8 107 PMC302Del Monte P, Bernasconi D, De Conca V, Randazzo M, Meozzi M, Badaracco B, Mesiti S, Marugo M.

Endocrine evaluation in patients treated with interferon-alpha for chronic hepatitis C.

Horm Res 44 3 105-9 1995

121


8 108 PMC204 Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E.

Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population.

Am J Gastro-enterol

96 1 157-64 2001

8 109 PMC41

Martín-Santos R, Díez-Quevedo C, Castellví P, Navinés R, Miquel M, Masnou H, Soler A, Ardevol M, García F, Galeras JA, Planas R, Solà R.

De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C.


27 3 257-65 2008

8 110Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, Jacobs S, Clement RP.

A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.


53 2000

8 111

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK.

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

Lancet 358 9286 958-65 2001

8 112

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J.

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

N Engl J Med 347 13 975-

82 2002

8 113

Bosques-Padilla F, Trejo-Estrada R, Campollo-Rivas O, Cortez-Hernández C, Dehesa-Violante M, Maldonado-Garza H, Pérez-Gómez R, Cabrera-Valdespino A.

Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial.

Ann Hepatol 2 3 135-9 2003

8 114

Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN, Mayet I, Khan MQ, Kessie G.

Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4.

Liver Int 24 6 568-74 2004

8 115

Bruno S, Cammà C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D, Colombo M, Craxì A, Mondelli MU, Pinzello G.

Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial.

J Hepatol 41 3 474-81 2004

8 116

Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group.

Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.


55 2004

8 117Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R, Siddique I, Al-Nakib B.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.


503 2004

122


8 118

Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS, Morgan TR, Bonkovsky HL, Lee WM, Dienstag JL, Ghany MG, Goodman ZD, Everhart JE; Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group.

Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

Gastro-enterology 126 4 1015-

23 2004

8 119

Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N, O'Brien CB, Lamour F, Lardelli P; PEGASYS Study NR16071 Investigator Group.

Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels.


32 2004

8 120 Herrine SK, Brown RS Jr, Bernstein DE, Ondovik MS, Lentz E, Te H.

Peginterferon alpha-2a combination therapies in chronic hepatitis C patients who relapsed after or had a viral breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of efficacy and safety.


26 2005

8 121

Jacobson IM, Gonzalez SA, Ahmed F, Lebovics E, Min AD, Bodenheimer HC Jr, Esposito SP, Brown RS Jr, Bräu N, Klion FM, Tobias H, Bini EJ, Brodsky N, Cerulli MA, Aytaman A, Gardner PW, Geders JM, Spivack JE, Rahmin MG, Berman DH, Ehrlich J, Russo MW, Chait M, Rovner D, Edlin BR.

A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C.

Am JGastro-enterol

100 11 2453-62 2005

8 122Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz AA, Madwar MA.

Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

Gut 54 6 858-66 2005

8 123

Lee SD, Yu ML, Cheng PN, Lai MY, Chao YC, Hwang SJ, Chang WY, Chang TT, Hsieh TY, Liu CJ, Chen DS.

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan.


91 2005

8 124

Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tamé MR, Montagnani M, Muratori R, Giovanelli S, Feletti V, Bacchi Reggiani ML, Roda E, Mazzella G.

Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study.


42 2005

8 125

Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A.

Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.

N Engl J Med 352 25 2609-

17 2005

8 126

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S.

Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.

Gastro-enterology 129 2 522-7 2005

123

CQ No No Author Title SecondaryTitle Volume Number Pages Year

8 127

Zeuzem S, Pawlotsky JM, LukasiewiczE, von Wagner M, Goulis I, Lurie Y,Gianfranco E, Vrolijk JM, Esteban JI,Hezode C, Lagging M, Negro F,Soulier A, Verheij-Hart E, Hansen B,Tal R, Ferrari C, Schalm SW,Neumann AU; DITTO-HCV StudyGroup.

International, multicenter, randomized,controlled study comparingdynamically individualized versusstandard treatment in patients withchronic hepatitis C.

J Hepatol 43 2 250-7 2005

8 128

Abergel A, Hezode C, Leroy V,Barange K, Bronowicki JP, Tran A,Alric L, Castera L, Bernard PH,Henquell C, Lafeuille H, Ughetto S,Darcha C, Chevallier M, Martineau N,Dubost S, Randl K, Dhumeaux D,Bommelaer G, Bonny C; Frenchmulticenter study group.

Peginterferon alpha-2b plus ribavirinfor treatment of chronic hepatitis Cwith severe fibrosis: a multicentrerandomized controlled trial comparingtwo doses of peginterferon alpha-2b.

J ViralHepat 13 12 811-

20 2006

8 129Berg C, Goncales FL Jr, Bernstein DE,Sette H Jr, Rasenack J, Diago M,Jensen DM, Graham P, Cooksley G.

Re-treatment of chronic hepatitis Cpatients after relapse: efficacy ofpeginterferon-alpha-2a (40 kDa) andribavirin.


40 2006

8 130

Berg T, von Wagner M, Nasser S,Sarrazin C, Heintges T, Gerlach T,Buggisch P, Goeser T, Rasenack J,Pape GR, Schmidt WE, Kallinowski B,Klinker H, Spengler U, Martus P,Alshuth U, Zeuzem S.

Extended treatment duration forhepatitis C virus type 1: comparing 48versus 72 weeks of peginterferon-alfa-2a plus ribavirin.


97 2006

8 131

Brandão C, Barone A, Carrilho F, SilvaA, Patelli M, Caramori C, Focaccia R,Pereira L, Pedroso M, Tatsch F, PessoaM; Pegasys Brazilian Study Group.

The results of a randomized triallooking at 24 weeks vs 48 weeks oftreatment with peginterferon alpha-2a(40 kDa) and ribavirin combinationtherapy in patients with chronichepatitis C genotype 1.

J ViralHepat 13 8 552-9 2006

8 132

Bronowicki JP, Ouzan D, Asselah T,Desmorat H, Zarski JP, Foucher J,Bourlière M, Renou C, Tran A, MelinP, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F,Lonjon-Domanec I, Pawlotsky JM.

Effect of ribavirin in genotype 1patients with hepatitis C responding topegylated interferon alfa-2a plusribavirin.


8 2006

8 133

Ciancio A, Picciotto A, Giordanino C,Smedile A, Tabone M, Manca A,Marenco G, Garbagnoli P, AndreoniM, Cariti G, Calleri G, Sartori M,Cusumano S, Grasso A, Rizzi R, GalloM, Basso M, Anselmo M, Percario G,Ciccone G, Rizzetto M, Saracco G.

A randomized trial of pegylated-interferon-alpha2a plus ribavirin withor without amantadine in the re-treatment of patients with chronichepatitis C not responding to standardinterferon and ribavirin.

AlimentPharmacolTher

24 7 1079-86 2006

8 134

Ferenci P, Formann E, Laferl H,Gschwantler M, Hackl F, Brunner H,Hubmann R, Datz C, Stauber R,Steindl-Munda P, Kessler HH, KlinglerA, Gangl A; Austrian Hepatitis StudyGroup.

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with orwithout amantadine in treatment-naïvepatients with chronic hepatitis Cgenotype 1 infection.

J Hepatol 44 2 275-82 2006

8 135

Meyer-Wyss B, Rich P, Egger H,Helbling B, Müllhaupt B, Rammert C,Gonvers JJ, Oneta C, Criblez D, RossiL, Borovicka J, Meyenberger C, ArnM, Renner EL; Swiss Association forthe Study of the Liver (SASL).

Comparison of two PEG-interferonalpha-2b doses (1.0 or 1.5 microg/kg)combined with ribavirin in interferon-naïve patients with chronic hepatitis Cand up to moderate fibrosis.


65 2006

8 136 Yenice N, Mehtap O, Gümrah M,Arican N.

The efficacy of pegylated interferonalpha 2a or 2b plus ribavirin in chronichepatitis C patients.

Turk JGastro-enterol

17 2 94-8 2006

124


8 137Yu ML, Dai CY, Lin ZY, Lee LP, HouNJ, Hsieh MY, Chen SC, Hsieh MY,Wang LY, Chang WY, Chuang WL.

A randomized trial of 24- vs. 48-weekcourses of PEG interferon alpha-2bplus ribavirin for genotype-1b-infectedchronic hepatitis C patients: a pilotstudy in Taiwan.

Liver Int 26 1 73-81 2006

8 138

Zeuzem S, Buti M, Ferenci P, Sperl J,Horsmans Y, Cianciara J, Ibranyi E,Weiland O, Noviello S, Brass C,Albrecht J.

Efficacy of 24 weeks treatment withpeginterferon alfa-2b plus ribavirin inpatients with chronic hepatitis Cinfected with genotype 1 and lowpretreatment viremia.

J Hepatol 44 1 97-103 2006

8 139

Carr C, Hollinger FB, Yoffe B, WakilA, Phillips J, Bzowej N, Leung J,Mirro K, Poordad F, Moore DH, GishRG.

Efficacy of interferon alpha-2binduction therapy before retreatmentfor chronic hepatitis C.

Liver Int 27 8 1111-8 2007

8 140

Diago M, Crespo J, Olveira A, Pérez R,Bárcena R, Sánchez-Tapias JM, Muñoz-Sánchez M, Romero-Gómez M.

Clinical trial: pharmacodynamics andpharmacokinetics of re-treatment withfixed-dose induction of peginterferonalpha-2a in hepatitis C virus genotype1 true non-responder patients.


26 8 1131-8 2007

8 141

Diago M, Olveira A, Solá R, Romero-Gómez M, Moreno-Otero R, Pérez R,Salmerón J, Enríquez J, Planas R,Gavilán JC, Del Olmo J, Uribarrena R,Sillero C, Benítez A, Sánchez-Galdón S,Dalmau B, Eraña L, Montoro M, PortuJ,Garijo JM, Barniol R, Domínguez A,Rota R, Olcoz JL, Antón M, PamplonaX,Casanovas T, Jiménez E, Huarte M, DíazF, Sánchez-Ruano J, Orive M, Muñoz-Sánchez M, Roset M.

Treatment of chronic hepatitis Cgenotype 1 with peginterferon-alpha2a(40 kDa) plus ribavirin under routineclinical practice in Spain: earlyprediction of sustained virologicalresponse rate.


25 8 899-906 2007

8 142

Kamal SM, El Kamary SS, ShardellMD, Hashem M, Ahmed IN,Muhammadi M, Sayed K, Moustafa A,Hakem SA, Ibrahiem A, Moniem M,Mansour H, Abdelaziz M.

Pegylated interferon alpha-2b plusribavirin in patients with genotype 4chronic hepatitis C: The role of rapidand early virologic response.


40 2007

8 143Kuboki M, Iino S, Okuno T, Omata M,Kiyosawa K, Kumada H, Hayashi N,Sakai T.

Peginterferon alpha-2a (40 KD) plusribavirin for the treatment of chronichepatitis C in Japanese patients.

J Gastro-enterolHepatol

22 5 645-52 2007

8 144

Marcellin P, Horsmans Y, Nevens F,Grange JD, Bronowicki JP, Vetter D,Purdy S, Garg V, Bengtsson L, McNairL, Alam J.

Phase 2 study of the combination ofmerimepodib with peginterferon-alpha2b, and ribavirin innonresponders to previous therapy forchronic hepatitis C.

J Hepatol 47 4 476-83 2007

8 145 Pearlman BL, Ehleben C, Saifee S.

Treatment extension to 72 weeks ofpeginterferon and ribavirin inhepatitisC genotype 1-infected slowresponders.


94 2007

8 146Shiffman ML, Salvatore J, Hubbard S,Price A, Sterling RK, Stravitz RT,Luketic VA, Sanyal AJ.

Treatment of chronic hepatitis C virusgenotype 1 with peginterferon,ribavirin, and epoetin alpha.

Hepatology 46 2 371-9 2007

125


8 147

Sjogren MH, Sjogren R Jr, Lyons MF, Ryan M, Santoro J, Smith C, Reddy KR, Bonkovsky H, Huntley B, Faris-Young S.

Antiviral response of HCV genotype 1 to consensus interferon and ribavirin versus pegylated interferon and ribavirin.


7 2007

8 148

Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL.

A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C.

Gut 56 4 553-9 2007

8 149

Angelico M, Koehler-Horst B, Piccolo P, Angelico F, Gentile S, Francioso S, Tarquini P, Vecchia RD, Ponti L, Pilleri G, Barlattani A, Grieco A, Soccorsi F, Guarascio P, Demelia L, Sorbello O, Rossi Z, Forlini G, Zaru S, Bandiera F; SMIEC II Investigators.

Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve patients with chronic hepatitis C.

Eur J Gastro-enterol Hepatol

20 7 680-7 2008

8 150

Bain VG, Lee SS, Peltekian K, Yoshida EM, Deschênes M, Sherman M, Bailey R, Witt-Sullivan H, Balshaw R, Krajden M; Canadian PEGASYS Study Group.

Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alpha-2a plus ribavirin.


28 1 43-50 2008

8 151

Lagging M, Langeland N, Pedersen C, Färkkilä M, Buhl MR, Mørch K, Dhillon AP, Alsiö A, Hellstrand K, Westin J, Norkrans G; NORDynamIC Study Group.

Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection.


45 2008

8 152 Napoli N, Giannelli G, Antonaci A, Antonaci S.

The use of different Peg-interferon alpha-2b regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not affect the achievement of sustained virological response.

J Viral Hepat 15 4 300-4 2008

8 153

Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, Bellia V, Del Poggio P, Fornaciari G, Ceriani R, Ramella G, Corradi C, Rossini A, Bruno S; Gruppo Epatologico Lombardo.

Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.


73 2008

8 154Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G.

Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active chronic hepatitis: a pilot study.

JInterferon Cytokine Res

28 10 623-9 2008

8 155Sood A, Midha V, Hissar S, Kumar M, Suneetha PV, Bansal M, Sood N, Sakhuja P, Sarin SK.

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian experience.

J Gastro-enterol Hepatol

23 2 203-7 2008

8 156Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, Naoumov NV.

Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon-alpha 2a plus ribavirin.


27 9 810-9 2008

126


8 157

von Wagner M, Hofmann WP, Teuber G, Berg T, Goeser T, Spengler U, Hinrichsen H, Weidenbach H, Gerken G, Manns M, Buggisch P, Herrmann E, Zeuzem S.

Placebo-controlled trial of 400 mg amantadine combined with peginterferon alfa-2a and ribavirin for 48 weeks in chronic hepatitis C virus-1 infection.


11 2008

8 158

Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL.

Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial.


93 2008

8 159

Zeuzem S, Yoshida EM, Benhamou Y, Pianko S, Bain VG, Shouval D, Flisiak R, Rehak V, Grigorescu M, Kaita K, Cronin PW, Pulkstenis E, Subramanian GM, McHutchison JG.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C.


17 2008

8 160

Andriulli A, Cursaro C, Cozzolongo R, Iacobellis A, Valvano MR, Mangia A, Minerva N, Bacca D, Stanzione M, Scuteri A, Montalto G, Andreone P.

Early discontinuation of ribavirin in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin.

J Viral Hepat 16 1 28-35 2009

8 161 Bressler B, Wang K, Grippo JF, Heathcote EJ.

Pharmacokinetics and response of obese patients with chronic hepatitis C treated with different doses of PEG-IFN alpha-2a (40KD) (PEGASYS).

Br J Clin Pharmacol 67 3 280-7 2009

8 162

Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourlière M, Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam J, Pawlotsky JM, Zeuzem S; PROVE2 Study Team.

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.

N Engl J Med 360 18 1839-

50 2009

8 163 Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, Sata M.

A randomized study of extended treatment with peginterferon alpha-2b plus ribavirin based on time to HCV RNA negative-status in patients with genotype 1b chronic hepatitis C.

Am J Gastro-enterol

104 1 70-5 2009

8 164

Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandão-Mello CE, Reddy KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A.

Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial.


40 2009

8 165

Kawaoka T, Kawakami Y, Tsuji K, Ito H, Kitamoto M, Aimitsu S, Kawakami H, Jeong SC, Imamura M, Aikata H, Takahashi S, Chayama K.

Dose comparison study of pegylated interferon-alpha-2b plus ribavirin in naïve Japanese patients with hepatitis C virus genotype 2: a randomized clinical trial.


24 3 366-71 2009

8 166

Langlet P, D'Heygere F, Henrion J, Adler M, Delwaide J, Van Vlierberghe H, Mulkay JP, Lasser L, Brenard R, Horsmans Y, Michielsen P, Laureys A, Nevens F.

Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatmentnaïve or relapsing chronic hepatitis C patients.


30 4 352-63 2009

127


8 167

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team.

Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection.

N Engl J Med 361 6 580-

93 2009

8 168

Roberts SK, Weltman MD, Crawford DH, McCaughan GW, Sievert W, Cheng WS, Rawlinson W, Desmond PV, Marks PS, Yoshihara M, Rizkalla B, Depamphilis JK, Dore GJ; Chariot Study Group.

Impact of high-dose peginterferon alfa-2a on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial.


55 2009

8 169 Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB.

Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin.


62 2009

8 170

Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S, McHutchison JG; MErimepodib TRiple cOmbination (METRO) Study Group.

Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders.


26 2009

8 171

Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, Atsumi H, Nakano S, Arakawa T.

Eight-week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response.

Liver Int 29 1 120-5 2009

8 172

Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP, Marino-Marsilia G, Fontanella L, Leandro G.

Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection.


22 2010

8 173 Brady DE, Torres DM, An JW, Ward JA, Lawitz E, Harrison SA.

Induction pegylated interferon alfa-2b in combination with ribavirin in patients with genotypes 1 and 4 chronic hepatitis C: a prospective, randomized, multicenter, open-label study.

Clin Gastro-enterol Hepatol

8 1 66-71.e1 2010

8 174 Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L.

Pioglitazone improves virological response to peginterferon alpha-2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance.

Liver Int 30 3 447-54 2010

8 175

Mecenate F, Pellicelli AM, Barbaro G, Romano M, Barlattani A, Mazzoni E, Bonaventura ME, Nosotti L, Arcuri P, Picardi A, Barbarini G, D'Ambrosio C, Paffetti A, Andreoli A, Soccorsi F; Club Epatologi Ospedalieri (CLEO) Group.

Short versus standard treatment with pegylated interferon alfa-2a plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BMC Gastro-enterol

10 21 2010

128


8 176

Méndez-Navarro J, Chirino RA, Corey KE, Gorospe EC, Zheng H, Morán S, Juarez JA, Chung RT, Dehesa-Violante M.

A randomized controlled trial of double versus triple therapy with amantadine for genotype 1 chronic hepatitis C in Latino patients.


35 2010

8 177Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E, Russo A, Colombo M.

Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C.

Gastroenterology 138 1 108-

15 2010

8 178 , , ,, , .

C

.

52 Suppl1 A157 2011

9 179 lamivudine38

Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group.

Lamivudine for patients with chronic hepatitis B and advanced liver disease.

N Engl J Med 351 15 1521-

31 2004

9 180 lamivudine15

Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai CL.

Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease.


303 2007

9 181 lamivudine33

Papatheodoridis GV, Dimou E, Dimakopoulos K, Manolakopoulos S, Rapti I, Kitis G, Tzourmakliotis D, Manesis E, Hadziyannis SJ.

Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.

Hepatology 42 1 121-9 2005

9 182 lamivudine18


Comparison of interferon and lamivudine treatment in Japanese patients with HBeAg positive chronic hepatitis B.


92 2007

9 183 entecavir4Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks I, Kane RL, Wilt TJ.

Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.


24 2009

2

131

2


1 49Chen CJ, Yang HI, Su J, Jen CL, YouSL, Lu SN, Huang GT, Iloeje UH;REVEAL-HBV Study Group.

Risk of hepatocellular carcinomaacross a biological gradient of serumhepatitis B virus DNA level.

JAMA 295 1 65-73 2006

3 55Bolondi L, Sofia S, Siringo S, GaianiS, Casali A, Zironi G, Piscaglia F,Gramantieri L, Zanetti M, Sherman M.

Surveillance programme of cirrhoticpatients for early diagnosis andtreatment of hepatocellular carcinoma:a cost effectiveness analysis.

Gut 48 2 251-9 2001

7 99Inoue A, Tsukuma H, Oshima A,Yabuuchi T, Nakao M, Matsunaga T,Kojima J, Tanaka S.

Effectiveness of interferon therapy forreducing the incidence ofhepatocellular carcinoma amongpatients with type C chronic hepatitis.

JEpidemiol 10 4 234-

40 2000

8 110Glue P, Rouzier-Panis R, Raffanel C,Sabo R, Gupta SK, Salfi M, Jacobs S,Clement RP.

A dose-ranging study of pegylatedinterferon alfa-2b and ribavirin inchronic hepatitis C. The Hepatitis CIntervention Therapy Group.


53 2000

8 111

Manns MP, McHutchison JG, GordonSC, Rustgi VK, Shiffman M,Reindollar R, Goodman ZD, Koury K,Ling M, Albrecht JK.

Peginterferon alfa-2b plus ribavirincompared with interferon alfa-2b plusribavirin for initial treatment of chronichepatitis C: a randomised trial.

Lancet 358 9286 958-65 2001

8 112

Fried MW, Shiffman ML, Reddy KR,Smith C, Marinos G, Gonçales FL Jr,Häussinger D, Diago M, Carosi G,Dhumeaux D, Craxi A, Lin A,Hoffman J, Yu J.

Peginterferon alfa-2a plus ribavirin forchronic hepatitis C virus infection.

N Engl JMed 347 13 975-

82 2002

8 113

Bosques-Padilla F, Trejo-Estrada R,Campollo-Rivas O, Cortez-HernándezC, Dehesa-Violante M, Maldonado-Garza H, Pérez-Gómez R, Cabrera-Valdespino A.

Peginterferon alfa-2a plus ribavirin fortreating chronic hepatitis C virusinfection: analysis of Mexican patientsincluded in a multicenter internationalclinical trial.

AnnHepatol 2 3 135-9 2003

8 114

Alfaleh FZ, Hadad Q, Khuroo MS,Aljumah A, Algamedi A, Alashgar H,Al-Ahdal MN, Mayet I, Khan MQ,Kessie G.

Peginterferon alpha-2b plus ribavirincompared with interferon alpha-2b plusribavirin for initial treatment of chronichepatitis C in Saudi patients commonlyinfected with genotype 4.

Liver Int 24 6 568-74 2004

8 115

Bruno S, Cammà C, Di Marco V,Rumi M, Vinci M, Camozzi M,Rebucci C, Di Bona D, Colombo M,Craxì A, Mondelli MU, Pinzello G.

Peginterferon alfa-2b plus ribavirin fornaïve patients with genotype 1 chronichepatitis C: a randomized controlledtrial.

J Hepatol 41 3 474-81 2004

132


8 116

Hadziyannis SJ, Sette H Jr, MorganTR, Balan V, Diago M, Marcellin P,Ramadori G, Bodenheimer H Jr,Bernstein D, Rizzetto M, Zeuzem S,Pockros PJ, Lin A, Ackrill AM;PEGASYS International Study Group.

Peginterferon-alpha2a and ribavirincombination therapy in chronichepatitis C: a randomized study oftreatment duration and ribavirin dose.

Ann InternMed 140 5 346-

55 2004

8 117Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R,Siddique I, Al-Nakib B.

Peginterferon alpha-2b plus ribavirinwith or without amantadine [correctionof amantidine] for the treatment ofnon-responders to standard interferonand ribavirin.

AntivirTher 9 4 499-

503 2004

8 118

Shiffman ML, Di Bisceglie AM,Lindsay KL, Morishima C, Wright EC,Everson GT, Lok AS, Morgan TR,Bonkovsky HL, Lee WM, Dienstag JL,Ghany MG, Goodman ZD, EverhartJE; Hepatitis C Antiviral Long-TermTreatment Against Cirrhosis TrialGroup.

Peginterferon alfa-2a and ribavirin inpatients with chronic hepatitis C whohave failed prior treatment.


23 2004

8 119

Zeuzem S, Diago M, Gane E, ReddyKR, Pockros P, Prati D, Shiffman M,Farci P, Gitlin N, O'Brien CB, LamourF, Lardelli P; PEGASYS StudyNR16071 Investigator Group.

Peginterferon alfa-2a (40 kilodaltons)and ribavirin in patients with chronichepatitis C and normalaminotransferase levels.


32 2004

8 120 Herrine SK, Brown RS Jr, BernsteinDE, Ondovik MS, Lentz E, Te H.

Peginterferon alpha-2a combinationtherapies in chronic hepatitis Cpatients who relapsed after or had aviral breakthrough on therapy withstandard interferon alpha-2b plusribavirin: a pilot study of efficacy andsafety.

Dig DisSci 50 4 719-

26 2005

8 121

Jacobson IM, Gonzalez SA, Ahmed F,Lebovics E, Min AD, Bodenheimer HCJr, Esposito SP, Brown RS Jr, Bräu N,Klion FM, Tobias H, Bini EJ, BrodskyN, Cerulli MA, Aytaman A, GardnerPW, Geders JM, Spivack JE, RahminMG, Berman DH, Ehrlich J, RussoMW, Chait M, Rovner D, Edlin BR.

A randomized trial of pegylatedinterferon alpha-2b plus ribavirin in theretreatment of chronic hepatitis C.

Am JGastro-enterol

100 11 2453-62 2005

8 122Kamal SM, El Tawil AA, Nakano T,He Q, Rasenack J, Hakam SA, SalehWA, Ismail A, Aziz AA, Madwar MA.

Peginterferon {alpha}-2b and ribavirintherapy in chronic hepatitis C genotype4: impact of treatment duration andviral kinetics on sustained virologicalresponse.

Gut 54 6 858-66 2005

8 123

Lee SD, Yu ML, Cheng PN, Lai MY,Chao YC, Hwang SJ, Chang WY,Chang TT, Hsieh TY, Liu CJ, ChenDS.

Comparison of a 6-month coursepeginterferon alpha-2b plus ribavirinand interferon alpha-2b plus ribavirinin treating Chinese patients withchronic hepatitis C in Taiwan.


91 2005

8 124

Lodato F, Azzaroli F, Brillanti S,Colecchia A, Tamé MR, MontagnaniM, Muratori R, Giovanelli S, Feletti V,Bacchi Reggiani ML, Roda E,Mazzella G.

Higher doses of peginterferon alpha-2badministered twice weekly improvesustained virological response indifficult-to-treat patients with chronichepatitis C: results of a pilotrandomized study.


42 2005

133


8 125

Mangia A, Santoro R, Minerva N,Ricci GL, Carretta V, Persico M,Vinelli F, Scotto G, Bacca D, AnneseM, Romano M, Zechini F, Sogari F,Spirito F, Andriulli A.

Peginterferon alfa-2b and ribavirin for12 vs. 24 weeks in HCV genotype 2 or3.

N Engl JMed 352 25 2609-

17 2005

8 126

von Wagner M, Huber M, Berg T,Hinrichsen H, Rasenack J, Heintges T,Bergk A, Bernsmeier C, Häussinger D,Herrmann E, Zeuzem S.

Peginterferon-alpha-2a (40KD) andribavirin for 16 or 24 weeks in patientswith genotype 2 or 3 chronic hepatitisC.

Gastro-enterology 129 2 522-7 2005

8 127

Zeuzem S, Pawlotsky JM, LukasiewiczE, von Wagner M, Goulis I, Lurie Y,Gianfranco E, Vrolijk JM, Esteban JI,Hezode C, Lagging M, Negro F,Soulier A, Verheij-Hart E, Hansen B,Tal R, Ferrari C, Schalm SW,Neumann AU; DITTO-HCV StudyGroup.

International, multicenter, randomized,controlled study comparingdynamically individualized versusstandard treatment in patients withchronic hepatitis C.

J Hepatol 43 2 250-7 2005

8 128

Abergel A, Hezode C, Leroy V,Barange K, Bronowicki JP, Tran A,Alric L, Castera L, Bernard PH,Henquell C, Lafeuille H, Ughetto S,Darcha C, Chevallier M, Martineau N,Dubost S, Randl K, Dhumeaux D,Bommelaer G, Bonny C; Frenchmulticenter study group.

Peginterferon alpha-2b plus ribavirinfor treatment of chronic hepatitis Cwith severe fibrosis: a multicentrerandomized controlled trial comparingtwo doses of peginterferon alpha-2b.


20 2006

8 129Berg C, Goncales FL Jr, Bernstein DE,Sette H Jr, Rasenack J, Diago M,Jensen DM, Graham P, Cooksley G.

Re-treatment of chronic hepatitis Cpatients after relapse: efficacy ofpeginterferon-alpha-2a (40 kDa) andribavirin.


40 2006

8 130

Berg T, von Wagner M, Nasser S,Sarrazin C, Heintges T, Gerlach T,Buggisch P, Goeser T, Rasenack J,Pape GR, Schmidt WE, Kallinowski B,Klinker H, Spengler U, Martus P,Alshuth U, Zeuzem S.

Extended treatment duration forhepatitis C virus type 1: comparing 48versus 72 weeks of peginterferon-alfa-2a plus ribavirin.


97 2006

8 131

Brandão C, Barone A, Carrilho F, SilvaA, Patelli M, Caramori C, Focaccia R,Pereira L, Pedroso M, Tatsch F, PessoaM; Pegasys Brazilian Study Group.

The results of a randomized triallooking at 24 weeks vs 48 weeks oftreatment with peginterferon alpha-2a(40 kDa) and ribavirin combinationtherapy in patients with chronichepatitis C genotype 1.

J ViralHepat 13 8 552-9 2006

8 132

Bronowicki JP, Ouzan D, Asselah T,Desmorat H, Zarski JP, Foucher J,Bourlière M, Renou C, Tran A, MelinP, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F,Lonjon-Domanec I, Pawlotsky JM.

Effect of ribavirin in genotype 1patients with hepatitis C responding topegylated interferon alfa-2a plusribavirin.


8 2006

8 133

Ciancio A, Picciotto A, Giordanino C,Smedile A, Tabone M, Manca A,Marenco G, Garbagnoli P, AndreoniM, Cariti G, Calleri G, Sartori M,Cusumano S, Grasso A, Rizzi R, GalloM, Basso M, Anselmo M, Percario G,Ciccone G, Rizzetto M, Saracco G.

A randomized trial of pegylated-interferon-alpha2a plus ribavirin withor without amantadine in the re-treatment of patients with chronichepatitis C not responding to standardinterferon and ribavirin.


24 7 1079-86 2006

134


8 134

Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, Hubmann R, Datz C, Stauber R, Steindl-Munda P, Kessler HH, Klingler A, Gangl A; Austrian Hepatitis Study Group.

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection.

J Hepatol 44 2 275-82 2006

8 135

Meyer-Wyss B, Rich P, Egger H, Helbling B, Müllhaupt B, Rammert C, Gonvers JJ, Oneta C, Criblez D, Rossi L, Borovicka J, Meyenberger C, Arn M, Renner EL; Swiss Association for the Study of the Liver (SASL).

Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.


65 2006

8 136 Yenice N, Mehtap O, Gümrah M, Arican N.

The efficacy of pegylated interferon alpha 2a or 2b plus ribavirin in chronic hepatitis C patients.

Turk J Gastro-enterol

17 2 94-8 2006

8 137Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL.

A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan.

Liver Int 26 1 73-81 2006

8 138

Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O, Noviello S, Brass C, Albrecht J.

Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia.

J Hepatol 44 1 97-103 2006

8 139

Carr C, Hollinger FB, Yoffe B, Wakil A, Phillips J, Bzowej N, Leung J, Mirro K, Poordad F, Moore DH, Gish RG.

Efficacy of interferon alpha-2b induction therapy before retreatment for chronic hepatitis C.

Liver Int 27 8 1111-8 2007

8 140Diago M, Crespo J, Olveira A, Pérez R, Bárcena R, Sánchez-Tapias JM, Muñoz-Sánchez M, Romero-Gómez M.

Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients.


26 8 1131-8 2007

8 141

Diago M, Olveira A, Solá R, Romero-Gómez M, Moreno-Otero R, Pérez R, Salmerón J, Enríquez J, Planas R, Gavilán JC, Del Olmo J, Uribarrena R, Sillero C, Benítez A, Sánchez-Galdón S, Dalmau B, Eraña L, Montoro M, Portu J, Garijo JM, Barniol R, Domínguez A, Rota R, Olcoz JL, Antón M, Pamplona X, Casanovas T, Jiménez E, Huarte M, Díaz F, Sánchez-Ruano J, Orive M, Muñoz-Sánchez M, Roset M.

Treatment of chronic hepatitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine clinical practice in Spain: early prediction of sustained virological response rate.


25 8 899-906 2007

8 142

Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K, Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M.

Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response.


40 2007

135


8 143Kuboki M, Iino S, Okuno T, Omata M, Kiyosawa K, Kumada H, Hayashi N, Sakai T.

Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic hepatitis C in Japanese patients.


22 5 645-52 2007

8 144

Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V, Bengtsson L, McNair L, Alam J.

Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C.

J Hepatol 47 4 476-83 2007

8 145 Pearlman BL, Ehleben C, Saifee S.Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis C genotype 1-infected slow responders.


94 2007

8 146Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, Luketic VA, Sanyal AJ.

Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha.

Hepatology 46 2 371-9 2007

8 147




7 2007

8 148



Gut 56 4 553-9 2007

8 149



Eur J Gastro-enterol Hepatol

20 7 680-7 2008

8 150




28 1 43-50 2008

8 151




45 2008

136


8 152 Napoli N, Giannelli G, Antonaci A, Antonaci S.


J Viral Hepat 15 4 300-4 2008

8 153




73 2008

8 154Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G.


JInterferon Cytokine Res

28 10 623-9 2008

8 155Sood A, Midha V, Hissar S, Kumar M, Suneetha PV, Bansal M, Sood N, Sakhuja P, Sarin SK.



23 2 203-7 2008

8 156Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, Naoumov NV.



27 9 810-9 2008

8 157




11 2008

8 158




93 2008

8 159




17 2008

8 160



J Viral Hepat 16 1 28-35 2009

137


8 161 Bressler B, Wang K, Grippo JF, Heathcote EJ.


Br J Clin Pharmacol 67 3 280-7 2009

8 162



N Engl J Med 360 18 1839-

50 2009

8 163 Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, Sata M.


Am J Gastro-enterol

104 1 70-5 2009

8 164




40 2009

8 165




24 3 366-71 2009

8 166


Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients.


30 4 352-63 2009

8 167

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team.


N Engl J Med 361 6 580-

93 2009

8 168


Impact of high-dose peginterferon alfa-2a on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial.


55 2009

8 169 Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB.

Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin.


62 2009

138


8 170

Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S, McHutchison JG; MErimepodib TRiple cOmbination (METRO) Study Group.



26 2009

8 171



Liver Int 29 1 120-5 2009

8 172




22 2010

8 173 Brady DE, Torres DM, An JW, Ward JA, Lawitz E, Harrison SA.


Clin Gastroenterol Hepatol

8 1 66-71.e1 2010

8 174 Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L.


Liver Int 30 3 447-54 2010

8 175


Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BMC Gastroenterol

10 21 2010

8 176




35 2010

8 177Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E, Russo A, Colombo M.

Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C.


15 2010

8 178 , , ,, , .

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52 Suppl1 A157 2011

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d th

e ris

k of

he

pato

cellu

lar

carc

inom

a.

2002

HB

sH

Be

RIA

HB

s

HB

e : 370

HB

s

HB

e :1,

991

HB

s

HB

e :9,

532

7:

30~6

5

:7

47,0

7911

,893

(25%

):

(HC

C)

HC

C

1) H

CC

(100

,000

)H

Bs

HB

e39

.1(9

5%C

I: 26

.2-5

6.1)

HB

sH

Be

324.

3(95

%C

I: 24

0.7-

427.

5)H

Bs

HB

e11

69.4

(95%

CI:

799.

9-16

50.9

)2)

Cox

HC

VH

Bs

HC

C9.

6(95

%C

I: 6.

0-15

.2)

HB

e60

.2(9

5%C

I: 35

.5-1

02.1

)

B HB

eB 1%

142

No

CQ

481

Iked

a K

, et

al.

Hep

atiti

s B

viru

s-re

late

d he

pato

cellu

lar

carc

inog

ene

sis a

nd it

s pr

even

tion.

2005

1) 2)-

1)

(HC

C)

48 HC

C 4

8

2)

(IFN

)(4

)

1)

/=3

9/9 49.5

/49

2)

1) 1

976~

1989

HB

217

IFN

160

146

HC

C48

HC

C98

HC

C1:

148

HC

CH

CC

7.2

HC

C11

.7

2) 1

983~

1990

HB

189

5713

. 6Ty

pe A

: IFN

HB

VTy

pe B

: IFN

HB

VTy

pe C

: IFN

HB

VTy

pe D

: IFN

HB

V

HB

V

1) H

CC

HC

C3

HB

V-D

NA

HC

CA

FP2)

HC

CTy

peA

15.

8%Ty

pe B

12

.5%

Type

C 3

3.3%

Type

D 4

0.4%

IFN

HB

V-D

NA

Type

HC

C

1)

2

2) H

BV

-DN

AH

CC

IFN

HB

V-D

NA

HC

C

491

Che

n C

J, et

al

; R

EVE

AL-

HB

V

Stud

y G

roup

.

Ris

k of

he

pato

cellu

lar

carc

inom

a ac

ross

a

biol

ogic

al

grad

ient

of

seru

m

hepa

titis

B

viru

s DN

A

leve

l.

2006

HB

V-D

NA

(HC

C)

3,65

37

30~6

5H

Bs H

CV

: HC

CH

CV

HC

C

1) 1

1.4

HC

C16

434

62)

HB

V-D

NA

HC

CH

CC

HB

V-

DN

A30

0cop

ies/

mL

108/

100,

000

1,00

0,00

0cop

ies/

mL

1,15

2/10

0,00

01.

3%14

.9%

3)

HB

eA

LT

HB

V-D

NA

HB

eA

LT

HC

C

143

No

CQ

501

Ishi

gur

o S,

et

al;

JPH

C

Stud

y G

roup

.

Seru

m

amin

otra

nsf

eras

e le

vel

and

the

risk

of

hepa

toce

llula

r ca

rcin

oma:

a po

pula

tion-

base

d co

hort

stud

y in

Ja

pan.

2009

-

19,8

12[ 18

,576

1,2

36(H

BV

479

HC

V73

7

HB

V+H

CV

20)]

6,92

012

,892

: ALT

(HC

C)

1)

109

(71

38)

HC

C2)

HC

C10

ALT

<30I

U/L

1.1%

ALT

30-6

9IU

/L11

.1%

ALT

70IU

/L24

.9%

1)

0.1%

2)

ALT

HC

C

511

Pagl

iar

o L,

et

al.

Nat

ural

h i

stor

y of

ch

roni

c he

patit

is C

.

1999

-1)

987

2) 4

,185

3) 1

,470

-

Res

earc

h qu

estio

n1)

C

2) C

3) C

4) C

MED

LIN

E (1

989.

1~19

97.1

2)

: chr

onic

hep

atiti

s, no

n-A

, no

n-B

hep

atiti

s, he

patit

is C

, nat

ural

hi

stor

y, c

ours

e, p

rogn

osis

, cas

e-co

ntro

l, co

hort

and

cros

s-se

ctio

nal s

tudi

es,

alco

hol,

iron,

tran

sam

inas

es, l

iver

ci

rrhos

is, H

CC

, gen

otyp

e, v

iraem

ia, a

nd

bloo

d do

nors

-

1)

38

(HC

C)

6~18

5 67%

(49~

91%

)2)

812

~44

HC

C15

~45

3) 1

31,

470

4~12

8~12

727

.9%

23.

5%11

.7%

4) C

1)

2)

‘non

-A,

non-

B

hepa

titis

’

144

No

CQ

521

Sang

iova

nni

A, e

t al

.

The

Nat

ural

H

isto

ry o

f C

ompe

nsat

ed

Cirr

hosi

s D

ue to

H

epat

itis C

V

irus:

a 17

-Y

ear

Coh

ort

Stud

y of

21

4 Pa

tient

s.

2006

23(1

1%)

9(

) (IFN

)

214

C [Chi

ld-

Pugh

A,

55(3

5)

(HC

C) RN

A]

: :R

NA

CP

B

(:

)

66(

)(

)H

CC

36(1

7%)

13(6

%)

50(2

3%)

36(1

7%)

2(1

%)

HC

C3.

9%2.

9%2.

0%0.

7%0.

1%4%

154

(72%

)H

CC

AFP

(>20

ng/m

L)(<

146

× 10

9/L)

(<4.

3g/d

L)73

(35%

)2.

0%

HC

V

11%

IFN (3

1%)

HC

C(

2.8%

1.4%

)(3

.9%

)

145

CQ

3

No

CQ

533

Zhan

g B

H, e

t al

.

Ran

dom

ize

d co

ntro

lled

trial

of

scre

enin

g fo

r he

pato

cellu

lar

carc

inom

a.

2004

()

()

2

AFP

()9

,757

9,44

3

:42

41

:62

.6%

63.3

%

:35

~59

B(H

Bs

)6

(AST

ALT

)

:(H

CC

)

: 199

31

~199

512

: 199

712 1998

12

1)

HC

C27

9.3/

100,

000

267.

0/10

0,00

01.

37(9

5%C

I: 0.

99-1

.89)

2) H

CC

100,

000

83.2

/131

.50.

63(9

5%C

I: 0.

41-0

.98)

1):

HC

C 8

671

3

()

12

GP

Shan

ghai

C

ance

r Reg

istry

2) B

2A

FP

HC

C37

%

543

Che

n TH

, et

al.

Ultr

asou

nd

scre

enin

g an

d ris

k fa

ctor

s for

de

ath

from

he

pato

cellu

lar

carc

inom

a in

a h

igh

risk

grou

p in

Tai

wan

.

2002

1=H

BsH

CV

AFP

(20

ng/m

L)A

ST(

40IU

/L)

ALT

(25

IU/L

)

2=

16

1 6

4,38

57

1)

4,3

852)

4

58

1)

:1

61

2)

:1

61

1)

4,38

568

458

9

2)

24%

(95%

CI:

52-6

2%)

3) 1.

57(9

5%C

I: 0.

94-4

.68)

2.66

(95%

CI:

1.68

-3.3

7)

4)

()

HB

HC

ALT

AFP

146

No

CQ

553

Bol

ondi

L, e

t al

.

Surv

eilla

nce pr

ogra

mm

e of

cirr

hotic

pa

tient

s for

ea

rly

diag

nosi

s an

d tre

atm

ent

of

hepa

toce

llula

r ca

rcin

oma:

a

cost

ef

fect

iven

ess a

naly

sis.

2001

6

AFP

313

104

: 198

93

~199

111

:

(HC

C)

: 198

93

~199

1 1

1

56

HC

C

1) H

CC

61(1

9.5%

)4.

1%

2) A

FPC

hild

-Pug

hB

C(

)3)

(P

=0.0

2)3

45%

31.7

%

1)

(ICER

)U

S$14

1,91

8/

2)

3)

US$

17,9

34

563

,.

.

1990

AFP

20ng

/mL

3

6

(HC

C)

878

1)

555

323

2)

294

529

3) H

Bs

:9.

3%7.

7%

702.

0mg/

dL3.

0g/d

L40

~70

50~7

0G

OT

GPT

50

HC

C1)

HC

C33

12(

5.1%

)34

1159

.22)

281

.9%

31.7

%(P

=0.0

001)

1)

2)

187

.8%

(5 1

3.1%

)

2

147

No

CQ

573

,.

.

2008

-

113,

992

39 ()

633

:81

%61

.1:

66%

66.8

:53

%62

.9:

30%

69.7

:20

%58

.0:

60%

71.1

:75

%61

.3:

60%

67.9

:80

%53

.9:

70%

64. 9

:70

%66

.6:

57%

65.2

1981

~199

516

,515

1981

~199

5

33,0

8919

96~2

004 64

,338

(5 )

1)

510

1536

.2%

9.1%

4.6%

18.2

%7.

3%4.

4%(P

<0.0

1)38

.8%

9.2%

4.6%

2)

540

.5%

40.4

%17

.3%

1)

2)

3)

335

.0~3

5.6%

533

.3~3

3.7%

148

CQ

4

No

CQ

(

)

1) 1

50H

Bs

low

-leve

l HB

s

6

2) 22

3)

6

4) B

ritis

h H

BsA

g W

orki

ng

Stan

dard

(0

.5IU

/mL)

5)

NIB

SC/U

KB

TS

HB

sAg

Mon

itor

Sam

ple

(0.1

25IU

/mL)

-H

Bs (

)

1) E

IAH

Bs

15H

Bs

2)

3)

584

Palm

er

DR

, et

al.

Var

iatio

n in

th

e se

nsiti

vity

of

HB

sAg

scre

enin

g ki

ts.

1996

1) 1

50H

Bs

10 a

ssay

s15

05

assa

ys14

9

low

-leve

l HB

s6

4 as

says

(Aus

zym

e M

onoc

lona

l, M

onol

isa

Ag

HB

s 2nd

ge

nera

tion,

Mur

ex H

BsA

g, O

rtho

HB

sAg

Test

Sys

tem

3)

51

assa

y(M

icro

Tra

k II

HB

sAg)

1

2)

assa

y(M

onol

isa

Ag

HB

s 2n

d ge

nera

tion)

795

assa

ys70

7 as

says

60-6

92

assa

ys50

-59

assa

y31

spec

imen

sH

Bs

3)

61

assa

y(A

uszy

me

Mon

oclo

nal)

1815

HB

s

3 as

says

HB

s10

4) B

ritis

h H

BsA

g W

orki

ng S

tand

ard

52

assa

ysco

nsis

tent

ly

unre

activ

e5)

NIB

SC/U

KB

TS H

BsA

g M

onito

r Sam

ple

3 as

says

(Bio

elis

a, E

nzyg

nost

, M

urex

)co

nsis

tent

ly re

activ

e5

assa

ysso

met

imes

reac

tive

6 as

says

cons

iste

ntly

un

reac

tive

15 H

Bs

-

149

No

CQ

594

Mot

te

A, e

t al

.

Eval

uatio

n of

the

clin

ical

pe

rform

anc

e of

the

Bec

kman

C

oulte

r A

cces

s A

bHB

sII

imm

unoa

ssay

for t

he

dete

ctio

n of

he

patit

is B

su

rface

an

tibod

ies.

2006

HB

sB

eckm

an

Cou

lter

Acc

ess

AbH

BsI

I im

mun

oass

ay

Abb

ott

Axs

ym te

stV

idas

1,20

7 (

232

HB

s HB

V 150

HB

s82

5)

(

) 1

HB

s : Acc

ess

Axs

ym

Acc

ess

Axs

ym Vid

as

: Acc

ess

Axs

ym

Acc

ess

Axs

ym Vid

as

1) A

cces

sA

xsym

95.8

%97

.8%

98.1

%96

.0%

99.0

%>1

00m

IU/m

L10

-100

mIU

/mL

<10m

IU/m

LA

cces

sA

xsym

>100

mIU

/mL

88.9

%10

-100

mIU

/mL

76.8

%<1

0mIU

/mL

96.2

%2)

51

Acc

ess

8(2

6H

BV

)15

(72

41

)

1)

HB

s

2)

604

Shih

LN

, et

al.

Seru

m

hepa

titis

B

viru

s DN

A

in h

ealth

y H

BsA

g-ne

gativ

e C

hine

se

adul

ts

eval

uate

d by

po

lym

eras

e ch

ain

reac

tion.

1990

HB

V-D

NA

(PC

R)

107

Nat

ion

al

Taiw

an

Uni

ver

sit

y Hos

pita

l

4562

44.9

(: 1

4-75

)6

HB

s : 198

81

~ 199

06

HB

V-D

NA

107

8(7

.5%

)H

BV

-DN

A

HB

sH

Bc

HB

e

HB

sH

Bc

:7.

4%(5

/68)

HB

s: 0

% (0

/6)

HB

cH

Be

: 25%

(1

/4)

HB

c: 0

% (0

/9)

: 10%

(2/2

0)

1)

HB

sH

BV

-D

NA

2)

()

HC

VH

BV

150

No

CQ

614

Gom

es

SA, e

t al

.

Det

ectio

n of

hep

atiti

s B

viru

s D

NA

in

hepa

titis

B

surfa

ce

antig

en-

nega

tive

seru

m b

y po

lym

eras

e ch

ain

reac

tion:

ev

alua

tion

of d

iffer

ent

prim

er

pairs

and

co

nditi

ons.

1996

ELIS

A(P

CR

)20

HB

sH

Bs

HB

sH

Bc

1) P

CR

HB

V-D

NA

0~50

%2)

HB

s87

~100

%

1) H

Bs

HB

V

2) H

Bs

HB

V

HB

VH

BV

-DN

APC

R

624

Toga

shi

H,

et a

l.

Wha

t can

be

reve

aled

by

ex

tend

ing

the

sens

itivi

ty

of H

BsA

g de

tect

ion

to

belo

w th

e pr

esen

t lim

it?

2008

-

1)

210

2)

368

-1)

49.

52)

49

1)

2)

EIA

HB

s B

HB

s

1)

HB

s2.

86%

(6/2

10)

2)

BC

7.69

%(5

/65)

BC

9.68

%(6

/62)

C8.

96%

(12/

134)

C10

.28%

(11/

107)

3) H

BV

-DN

APC

R9

B

1) H

Bs

B(P

<0.0

05)

2)

HB

V

151

No

CQ

634

Col

in

C, e

t al

; H

EPA

TITI

S G

roup

.

Sens

itivi

ty

and

spec

ifici

ty

of th

ird-

gene

ratio

n he

patit

is C

vi

rus

antib

ody

dete

ctio

n as

says

: an

anal

ysis

of

the

liter

atur

e.

2001

HC

V

132 10 H

CV

RIB

A PCR

-

1)

2) M

EDLI

NE

Exce

rpta

M

edic

a

3)

:he

patit

is c

, se

rodi

agno

sis,

sens

itivi

ty,

spec

ifici

ty

1)

ELIS

A98

.9%

(95%

CI:

94-1

00)

100%

2)

RIB

A3

78.8

%(9

5%C

I: 65

-89)

1)

HC

V

2)

PCR

3)

100%

644

Sher

man

M,

et a

l.

Scre

enin

g fo

r he

pato

cellu

lar

carc

inom

a in

chr

onic

ca

rrier

s of

hepa

titis

B

viru

s: in

cide

nce

and

prev

alen

ce

of

hepa

toce

llula

r ca

rcin

oma

in a

Nor

th

Am

eric

an

urba

n po

pula

tion.

1995

6

AFP

AFP

1,06

9(A

FP:

531

AFP

+:

538

)

(

)

1989

2~1

994

3

HB

V 39(±

12)

65% 71

%

1) 1

82)

GP(

)

3) L

iver

Can

cer

Scre

enin

g

1) (H

CC

)

2)

1)

26(6

-60

)2)

4%

AFP

9%

3) 3

HC

C28

1/10

0,00

0HB

V

11H

CC

( 4

70/1

00,0

00)

657

/100

,000

4) H

CC

5(

214

/100

,000

)5)

)

HC

C64

.3%

91.4

%71

.4%

93.8

%

1)

HC

C

2)

(RC

T)fe

asib

ility

st

udy

3) R

CT

2H

CC

AFP

152

No

CQ

654

Tong

M

J, et

al

.

Surv

eilla

nce

for

hepa

toce

llula

r ca

rcin

oma

in p

atie

nts

with

ch

roni

c vi

ral

hepa

titis

in

the

Uni

ted

Stat

es o

f A

mer

ica.

2001

HC

VH

BV

AFP

(US)

AFP

US

602

HC

=429

/HB

=160

/HB

+HC

=13

356

(59%

)24

6(3

5%)

51(±

14)

(HC

C)

1) A

FP6

US

131

HC

C2)

HC

CU

S10

0%98

%(P

PV)

78%

AFP

RO

C65

%90

%A

FP13

ng/m

L

3)

AFP

HC

C74

%10

%A

FPPP

V12

%R

OC

65%

90%

4) U

SPP

V78

%10

0%98

%H

CC

24(7

7%)

16.7

±19.

4

1) H

CC

AFP

US 10

0%

HC

C

2) U

S1

CT

US

AFP

CT

AFP

US

PPV

3)

AFP

PPV

664

,.

.

1995

7,02

2(1

981

~198

7

)

40~6

9:

88.9

%99

.4%

1)

2)

3)

153

CQ

5

No

CQ

675

,.

1.

2009

171

Finn

ch

amb

ers

Scan

por

tape

685

Erdm

ann

SM

, et

al.

Alle

rgic

co

ntac

t de

rmat

itis

due

to

met

hyld

ibr

omo

glut

aron

itril

e in

Eux

yl

K 4

00 in

an

ultra

soni

c ge

l.

2001

162

RW

TH(E

uxyl

K 4

00)

met

hyld

ibro

mo

glut

aron

itrile

()

154

CQ

6

No

CQ

696

Riv

era- Sa

nfel

iz

G, e

t al

.

Sing

le-

pass

pe

rcut

aneo

us li

ver

biop

sy fo

r di

ffuse

liv

er

dise

ase

usin

g an

au

tom

ated

de

vice

: ex

perie

nce

in 1

54

proc

edur

es.

2005

(INR

AD

18

G

Expr

ess

core

ne

edle

bi

opsy

sy

stem )

153

Vet

era

ns

Affa

irs

Med

ical

C

ent

er

52 (

:30

-83

)

2000

1~2

003

2V

eter

ans A

ffairs

Med

ical

Cen

ter

138

(90.

2%)

C INR

1.5

>70,

000/

3

1)

:

4

2)

:

3)

:

1cm

41.

2%28

(18.

2%)

32

(1.3

%)

706

Gilm

ore

IT, e

t al

.

Indi

catio

ns, m

etho

ds,

and

outc

omes

of

pe

rcut

aneo

us li

ver

biop

sy in

En

glan

d an

d W

ales

: an

audi

t by

the

Brit

ish

Soci

ety

of

Gas

troen

tero

logy

and

th

e R

oyal

C

olle

ge o

f Ph

ysic

ians

of

Lon

don.

1995

1,50

0he

alt

h dist

rict

18

9

806

694

60-6

9

heal

th d

istri

ct 1

89B

ritis

h So

ciet

y of

Gas

troen

tero

logy

11

1991

110

:

79%

(150

0/18

9)1)

56

3(3

8%)

507

(34%

)2)

Tr

u-cu

t typ

e (A

bbot

t) 66

%M

engh

ini t

ype

62%

()

3)

83%

exce

llent

()

satis

fact

ory(

)5%

26(1

.7%

): 11

19

INR (20

)Tr

u-cu

t/

:2

(44

:71

:

)3

()

1,50

00.

13~0

.33%

1) 1

991

1

40%

62%

2)

155

No

CQ

716

Picc

ini

no

F, e

t al

.

Com

plic

atio

ns

follo

win

g pe

rcut

aneo

us li

ver

biop

sy. A

m

ultic

entr

e retro

spec

tive

stud

y on

68,

276

biop

sies

.

1986

68,2

76Li

ver U

nit 36

Live

r Uni

t10

400

36 L

iver

Uni

t19

73~1

983

50%

50,0

00/

3

Men

ghin

i typ

e 60

,611

Tru-

cut t

ype

7,37

2V

im-S

ilver

man

ty

pe 2

93

4,52

79,

367

18,7

3522

,729

1,75

511

,163

147

(2.2

%)

(

)[

]Men

ghin

i typ

e 12

0(2

.0%

)Tr

u-cu

t typ

e 26

(3.5

%)

Vim

-Silv

erm

an ty

pe 1

(3.4

%)

[]

2(0

.44%

)22

(2.3

4%)

52(2

.78%

)52

(2.2

9%)

5(2

.85%

)14

(1.2

5%)

6(0

.009

%)

100,

000

9

[]M

engh

ini t

ype

3Tr

u-cu

t typ

e 3

[]

33

1) 1

970~

80

2)

726

Mye

rs R

P,

et a

l.

Util

izat

ion

rate

s, co

mpl

icat

ion

s and

co

sts o

f pe

rcut

aneo

us li

ver

biop

sy: a

po

pula

tion

-bas

ed

stud

y in

clud

ing

4275

bi

opsi

es.

2008

1994

~20

029

4,27

5

(3,6

27 )

(

)

43%

50

9

9

(

)

(99

%)

:

32(0

.75%

)[

22(6

9%)

15(4

7%)

8(2

5%)

3(9

%)

6(1

9%)]

1110

32

21

(91%

vs.

94%

)6

(0.1

4%)

51

156

No

CQ

736

Viv

as S

, et

al.

Am

bula

tor

y liv

er

biop

sy:

com

plic

ati

ons a

nd

evol

utio

n in

264

ca

ses.

1998

(

)

4

264

( :

114

)

(

)

65%

42

:66

%

7%

5% (

)

:

264

5(

13

1) 18

%83

%24

(1.9

% v

s. 1.

7%)

1) 0.

9-3.

7%(1

978~

199

5)

2)

18%

2%

746

Suga

no S

, et

al.

Inci

denc

e of

ul

traso

und

-det

ecte

d in

trahe

pati

c hem

atom

as d

ue to

Tr

u-cu

t ne

edle

liv

er

biop

sy.

1991

(

)

45

75

2

: 24-

72

: 22-

742

:

1)

9(2

0%)

13(1

7%)

(18

.3%

)2)

157

No

CQ

756

Cat

ure

lli

E, e

t al

.

Perc

utan

eou

s bio

psy

in d

iffus

e liv

er

dise

ase:

in

crea

sing

di

agno

stic

yi

eld

and

decr

easi

ng

com

plic

ati

on ra

te b

y ro

utin

e ul

traso

und

asse

ssm

ent o

f pu

nctu

re

site

.

1996

753

Cas

a So

lliev

o de

lla

Soffe

renz

a :40

,000

/3 40%

1) 7

45/7

53

2)

:1

(0.1

3%)

33.

5%0.

9%3)

1

1)

0.13

%(0

.21-

5.9%

)

2)

0-0.

33%

766

Froe

hlic

h F,

et

al.

Prac

tice

and

com

plic

ati

ons o

f liv

er

biop

sy.

Res

ults

of

a natio

nwid

e su

rvey

in

Switz

erla

nd.

1993

3,50

180

1) 2

8025

2(

90.0

%)

2)

165

3,50

13)

0.

31%

(5

31

need

le ru

ptur

e1)

4)

3(0

.08%

)

1)

2)

158

No

CQ

776

van

der

Poor

ten

D,

et a

l.

Twen

ty-

year

aud

it of

pe

rcut

aneo

us li

ver

biop

sy in

a

maj

or

Aus

tralia

n te

achi

ng

hosp

ital.

2006

24 62%

46%

1,39

8(1

986~

199

5:

444

1996

~20

05:

954

)

1

1,39

8:

213

799

204 67

%/

33%

18~8

8(

43)

59.6

%(1

996~

200

5)

66%

C (37.

8%)

B(2

6.4%

)

(22.

2%)

1996

~200

5C

onco

rd R

epat

riatio

n G

ener

al H

ospi

tal

1986

~199

5 : 188

:2

Min

or(

):

Maj

or(

):

20g/

L

1990

166

(13.

6%)

12(1

%)

101

13

(0.2

5%)

100×

109/

L16

747

(9.8

%)

1018

.5%

1010

.8%

101.

35%

100.

78%

(P=0

.508

)10

(63.

9%)

1) 2

41,

398

1%0.

25%

2)

1% (0.3

2~0.

59%

)

786

Lind

or

KD

, et

al.

The

role

of

ultra

sono

gra

phy

and

auto

mat

ic-

need

le

biop

sy in

ou

tpat

ient

pe

rcut

aneo

us li

ver

biop

sy.

1996

(

)

(US)

Tru-

cut

US

836

(489

347

)(1

) Tru

-cu

tU

S20

4 (2

) Tr

u-cu

tU

S

216

(3)

US

209

(4)

US

207

( ) (

)

:45

%50

(16-

90)

:67

%40

(13-

72)

54%

47(1

3-90

)

4.7%

43.5

%7.

2%

(79.

4%

vs. 1

8.2%

)

:(

)489

Hos

pita

l C

linic

o y

Prov

inci

al d

e B

arce

lona

()3

47

:

50,0

00×1

06 /L10

g/dL

3

: 199

21

~199

41

:15

40H

g80

Hg

25%

/ 2

/ 3

30H

g80

Hg

( )

1)

1.3%

(11

/836

)U

S2

US

9(P

=0.0

4)2)

U

S9

US

18(P

=0.0

7)3)

U

S1

4)

US

37%

US

50%

(P=0

.003

)5)

U

S(

Tru-

cut

)

US

Tru-

cut

(P<0

.005

)6)

2

7)

121

1) U

S

US

2)

4

159

No

CQ

796

Mon

tal

to

G, e

t al

.

Perc

utan

eou

s liv

er

biop

sy: a

sa

fe

outp

atie

nt

proc

edur

e?

2001

1,58

11

1993

~199

9

1,31

826

3

:(

):

( )

1)

01

2)

01

3)

15.9

%15

.2%

4)

31

5)

1)

2) 1

806

Chu

ah SY

, et

al.

A natio

nwid

e su

rvey

of

liver

bi

opsy

--is

ther

e a

need

to

incr

ease

re

sour

ces,

man

pow

er

and

train

ing?

1994

( )

364

1 INR

2

81.3

%20

6(

8011

1330

5319

)95

%20

/5.

2/10

,000

5.6/

1,00

02

160

CQ

7

No

CQ

817

Cam

mà

C,

et a

l.

Inte

rfer

on

and

prev

entio

n of he

pato

cellu

lar

ca

rcin

oma

in v

iral

cirr

hosi

s: an

ev

iden

ce-

base

d ap

proa

ch.

2001

[

(RC

T)

]

(IFN

)

1) H

C

3RC

T11 R

CT

3,10

9

(HC

C)

356

2) H

B 7R

CT

1,50

5H

CC

122

-C

B

1) M

EDLI

NE(

1985

~199

9)

: hep

atoc

ellu

lar c

arci

nom

a,

inte

rfer

on, c

irrho

sis,

clin

ical

tria

l, co

hort

stud

y2)

(199

5~19

99)

:R

CT

RC

T H

CC

HC

C

1) IF

NC

SVR

()

2) H

CV

HBV

HC

C12

.8%

(95%

CI:

8.3-

17.2

)6.

4%(9

5%C

I: 2.

8-10

.0)

3) H

CV

SVR

HC

Cno

n re

spon

der

(RD

: 11.

8%, 9

5%C

I:5.9

-14.

2)4)

HC

HC

C6.

8-37

.7%

1) C

B

HBV

HC

C

2) IF

NC

B

3) IF

N RC

TR

CT

3

827

Sung

JJ

, et

al.

Met

a-an

alys

is:

Trea

tmen

t of

hep

atiti

s B

infe

ctio

n re

duce

s ris

k of he

pato

cellu

lar

ca

rcin

oma.

2008

:

1) (IFN

)[

(PEG

-IF

N) ]

2) ( )

1) IF

N:

2,74

22)

:2,

289

-

1) IF

N:

1997

~200

712

(1

10 1)2,

742

(71

.0%

36.7

4.7~

8.9

)2)

:20

04~2

007

5(

22

1)2,

289

(78

.6%

42.8

2.7~

8.2

)5

1

1):

BIF

N(P

FG-IF

N)

(

)

(HC

C)

2):

HC

C3)

:

B HC

C

1) IF

N:

Pool

ing

0.66

(95%

CI:

0.48

-0.8

9)34

%

2):

Pool

ing

0.22

(95%

CI:

0.10

-0.5

0)78

%

HBe

HBe

3):

5(

: 1~5

5)

(3

)

IFN

(: 0

.64

95%

CI:

0.44

-0.9

3)

1) IF

N BH

CC

2)IF

N

3) 4) 5)

161

No

CQ

837

Miy

ake

Y,

et a

l.

Met

a-an

alys

is:

the

effe

ct

of

inte

rfero

n on

de

velo

pme

nt o

f he

pato

cell

ular

ca

rcin

oma

in p

atie

nts

with

ch

roni

c he

patit

is B

vi

rus

infe

ctio

n.

2009

(IFN

)

8 1,30

31)

(RC

T)3

RC

T5

2)

3

3

1 1

-=h

epat

itisB

, in

terfe

ron,

HC

C

PubM

ed19

981

~200

712

: 1

) IFN

2)

HC

VH

IV

3)

(HC

C)

4)

HC

C

HC

C

1) H

CC

(RD

: 5.

0%;

95%

CI:

9.4

- 0.

5)2)

(RD

: 8.

5%; 9

5%C

I: 13

.6 -

3.6)

1) P

ubM

ed8

2)

8IF

N

3) IF

N

4) H

BV

-DN

A

847

Lin

SM,

et a

l.

Long

-term

be

nefic

ial

effe

ct o

f in

terfe

ron

ther

apy

in

patie

nts

with

ch

roni

c he

patit

is B

vi

rus

infe

ctio

n.

1999

()

(IFN

)

(67

) 31 IFN

36 IFN

101

( 67 34)

(

)

IFN

(31

)32±

832

±29 IF

N+

(36

)31±

641

±36

(34

)32±

641

±58

17~5

5H

be

: Liv

er R

esea

rch

Uni

t: :

IFN

6.9±

3.2

IFN

+7.

8±2.

87.

4±2.

4

(HC

C)

1)

241

(4.2

%)

367

(19.

4%)

80

215

(23.

8%)

(P>0

.05)

2)

67H

CC

1(1

.5%

)34

HC

C4

(12%

)(P

=0.0

43)

3)

14

1098

%85

%

1)

(

)2

2)

3)

2

162

No

CQ

857

Inte

rna

tiona

l In

terf

eron

-

Hep

ato

cell

ular

C

arci

nom

a Stud

y Gro

up.

Effe

ct o

f in

terfe

ron-

alph

a on

pr

ogre

ssio

n of

ci

rrhos

is

to

hepa

toce

llul

ar

carc

inom

a: a

re

trosp

ecti

ve c

ohor

t st

udy.

1998

(IFN

) [ 4.

2%(1

60

)

2a 28%

(10

7)

2b

281

356

(B

and/

or C

)C

hild

-Pug

h A

: C :IF

N

(

):

:21

: :1

3

1)

(HC

C)

10. 3

%(2

9/28

1)18

.5%

(66/

356)

1.99

(95%

CI:

1.09

-3.6

4)2)

HC

HC

C9.

1%(2

1/23

2)18

.5%

(48/

259)

3.14

(95%

CI:

1.46

-6.8

0)

3) H

BH

CC

16%

(8/4

9)19

%(1

8/97

)0.

98(9

5%C

I: 0.

33-2

.92)

CB

IFN

2)

3)

4)

2

867

Nis

higu

chi S

, et

al.

Ran

dom

ised

tria

l of

effe

cts o

f in

terfe

ron-

alph

a on

in

cide

nce

of

hepa

toce

llul

ar

carc

inom

a in

chr

onic

ac

tive

hepa

titis

C

with

ci

rrhos

is.

1995

(RC

T) (

)

(IFN

)

90 ( 45 45

)

:28

/17

54.7

±5.8

:23

/22

57.3

±6.9

1) C

2)

HB

s

: 198

81

~199

26

: 2~7

(HC

C)

1) H

CC

19:

217

( P=0

.002

)2)

0.

067(

95%

CI:

0.00

9-0.

530)

3)

52

2H

CC

:

1)

IFN

RC

T: IF

NH

CC

2)

80%

163

No

CQ

877

Azz

arol

i F,

et a

l.

Inte

rfer

on

plus

rib

aviri

n an

d in

terf

eron

al

one

in

prev

entin

g he

pato

cellu

lar

ca

rcin

oma:

a pr

ospe

ctiv

e st

udy

on

patie

nts

with

HC

V

rela

ted

cirr

hosi

s.

2004

(RC

T)

()

HC

V

(IFN

)+

(RBV

)

60 IFN

30(T

G:

treat

men

t gr

oup)

30(C

G:

cont

rol

grou

p] 1IF

N

41 (OTC

G: o

ld

treat

men

t co

ntro

l gr

oup)

: 60

(35

25)

55.7

±1.7

OTC

G:

2714

55.0

±1.1

:

HC

V

: 5

(HC

C)

1)(T

G)

1IF

N+R

BV6

2) O

TCG

IFN

619

8(S

R)

OTC

GIF

NA

gNO

R-P

I(Ag

stai

ned

nucl

eola

r or

gani

zer r

egio

n -p

rolif

erat

ive

inde

x)3)

AgN

OR

-PI>

2.5%

HC

C9/

35(2

6%)

AgN

OR

-PI<

2.5%

2/66

(3%

)

TG21

(VR

)13

SR4)

HC

CTG

CG

9O

T CG

non-

resp

onde

r()

2TG

CG

(P<0

.003

)O

TCG

CG

(P<0

.004

)

5)(C

G)

HC

C5%

6)TG

IFN

RBV

1) R

CT

21

RC

T

(AgN

OR

-PI)

RC

T

2) IF

N+R

BVH

CC

(RC

T)

3) IF

NR

BV

4) R

CT

AgN

OR

-PI

887

Benv

egnù

L,

et

al.

Ret

rosp

ecti

ve a

naly

sis

of th

e ef

fect

of in

terf

eron

th

erap

y on

th

e cl

inic

al

outc

ome

of

patie

nts

with

vira

l ci

rrho

sis.

1998

(IFN

)

189

(88

101

)

:12

2(6

4.5%

)67

(35.

5%)

58.2

±8.2

(: 3

6-75

)H

Bs28

(14.

8%)

HC

V15

2(8

0.4%

)H

BsH

CV 9

(4.8

%)

:59

2956

.7±8

.0 :63

3859

.5±8

.3

:1

1986

~199

3

Chi

ld-P

ugh

AB

C

: : 198

6~19

9371

.5(

: 23-

125

): IF

N71

.971

.4

1)

Chi

ld-

Pugh

2)

(HC

C)

3)

1) C

hild

-Pug

h7

(7.9

%)

22(2

1.8%

)(P

<0.0

1)2)

HC

C5

(5.6

%)

27(2

6.7%

)3

(3.4

%)

20(1

9.8%

)(P

<0.0

01, P

<0.0

05)

3)IF

N

4)H

Bs2

HC

V

5)SV

R(

)H

CC

SVR

1)IF

N

3

2)

(95%

CI)

(P

)3)

Fish

er

164

No

CQ

897

Yos

hida

H,

et a

l.

Inte

rfer

on

ther

apy

redu

ces t

he

risk

for

hepa

toce

llul

ar

carc

inom

a:

natio

nal

surv

eilla

nce

prog

ram

of

cirr

hotic

an

d no

ncirr

hotic

pa

tient

s w

ith

chro

nic

hepa

titis

C

in Ja

pan.

IH

IT S

tudy

G

roup

. In

hibi

tion

of Hep

atoc

arci

noge

nesi

s by

In

terf

eron

Th

erap

y.

1999

(IFN

) 2,40

0

84%

14%

IFN

2%

:48

0 M

U

(firs

t qu

artil

e32

4 M

U;

third

qu

artil

e70

2 M

U) :

160

(firs

t qu

artil

e94

; thi

rd

quar

tile

168

)

2,89

0 C

(2,

400

490

)

8

:1,

531

869

49.5

±11.

3:

270

220

53.6

±11.

2

:8

1986

C

: 3,2

2316

11

172

4.3

(HC

C)

1) H

CC

: 1

.10%

(89

/2,4

00)

3.1

7%(5

9/4

90) (

P<0.

01)

HC

C2)

F0F1

0.5%

F47.

9%F2

(P=0

.012

8)F3

(P=0

.001

1)3)

IFN

HC

C(

0.51

6, 9

5%C

I: 0.

358-

0.74

2)(

0.19

7,95

%C

I: 0.

099-

0.39

2)A

LT(

0.19

7, 9

5%C

I: 0.

104-

0.37

5)A

LT2

(0.

358,

95%

CI:

0.20

6-0.

622)

1)IF

NH

CC

2) 3) F

0F1

IFN

HC

C

4) H

CV

HC

C

165

No

CQ

907

Val

la

DC

, et

al.

Trea

tmen

t of

hep

atiti

s C

viru

s-re

late

d ci

rrho

sis:

a ra

ndom

ized

, con

trolle

d tri

al o

f in

terf

eron

al

fa-2

b ve

rsus

no

treat

men

t.

1999

(RC

T)

()

(IFN

)

2b 3,00

0,00

0

324 ]

99(IF

N

47

52)

8

:1.

55/

2.36

:56

57

:18

~75

1

2H

CV

()

(B

)H

I V>5

0×10

3 /3

>1,2

00/

3IF

N : 199

3~19

95: 1

993~

1997

(RC

T4

7219

979

)

RC

T: [

]

(44 48

AST

ALT )

[] (

48~7

2

)

AFP

: ( )

(HC

C)

1)47

62

2)A

FP

3) H

CC

59

65

107

3: I

FN87

%(

) 35

1)H

CV

HC

V-R

NA

2) R

CT

IFN

3) R

CT

72

IFN

1997

9

166

No

CQ

917

Maz

zel

la

G, e

t al

.

Alp

ha

inte

rfero

n tre

atm

ent

may

pr

even

t he

pato

cell

ular

ca

rcin

oma

in H

CV

-re

late

d liv

er

cirrh

osis

.

1996

(IFN

)

347

( 227

120

)

1

213

51 HB

V/H

CV

34/1

9328

/92

(HC

V AB

HC

V

) HB

VH

CV

:1

HB

VH

CV

(Chi

ld-P

ugh

A)

: 198

4~19

94: [

] HB

V49

/HC

V32

[] H

BV

48/H

CV

34

(HC

C)

1) H

CC

20(H

BV

6/H

CV

14)

2) H

CC

(RR

=9.6

, P<0

.007

)IF

N(R

R=4

.4, P

<0.0

2)3)

IFN

HB

VH

CV

4) H

CC

IFN

4.4

(95%

CI:

1.5-

13.5

)H

BV

4.9

(95%

CI:

0.2-

95.2

)/HC

V4.

0 (9

5%C

I: 1.

2-13

.5)

5)

IFN

1) H

CV

IFN

ALT

2)

HC

C

HC

V

3)

HB

VH

CC

4) H

BV

927

Iked

a K

, et

al.

Ant

icar

cin

ogen

ic

impa

ct o

f in

terfe

ron

on p

atie

nts

with

ch

roni

c he

patit

is

C: a

larg

e-sc

ale

long

-te

rm st

udy

in a

sing

le

cent

er.

2006

(IFN

)(

1,23

8 IFN

30)

2,16

6( 1,

654

512

)

:67

.1%

50:

60.7

%53

:H

Bs

HC

V :(H

CC

)H

BV

: 197

0~20

04(

2004

51

): 1

0.7

(: 0

.1-3

3.6)

HC

C

1)

HC

C5.

8%(9

6/1

,654

)20

.1%

(103

/512

)2)

5

HC

C2.

6%4.

6%10

5.8%

12.7

%15

13.9

%23

.9%

(P<0

.000

1)3)

HC

CF1

F2~F

38.

68(9

5%C

I: 5.

08-1

4.81

)50

2.64

(95%

CI:

1.58

-4.

42)

2.38

(95%

CI:

1.56

-3.7

0)

4)

3.1%

(52

/1,6

54)

12.5

%(6

4/5

12)

1)

C IFN

HC

C

2) IF

N(2

:24

03

: 56

)3)

4) 2

23(1

0.3%

)

167

No

CQ

937

Shira

tori

Y, e

t al

; To

kyo- C

hib

a Hep

atit

is

Res

ear

ch

Gro

up.

Ant

ivira

l th

erap

y fo

r ci

rrhot

ic

hepa

titis

C

: as

soci

atio

n w

ith

redu

ced

hepa

toce

llul

ar

carc

inom

a de

velo

pme

nt a

nd

impr

oved

su

rviv

al.

2005

(IFN

)

2a:

6~9M

U3

/

32~8

8)]

C 345

( 271 74

)

25

137

208

:10

216

957 :

3539 61

:H

CV

-RN

A(C

hild

-Pug

hA

) >5

0,00

0/3

>3,0

00/

3

: HB

V

: 199

6~20

02: 6

.8(

: 0.0

4-10

.4)

(HC

C)

1) S

VR

()

23.6

%(6

4/2

71)

2) H

CC

: 119

[84

(31.

0%)

35(4

7.3%

)]3)

(

0.65

, 95%

CI:

0.43

-0.

97, P

=0.0

3)SV

R(

0.31

, 95%

CI:

0.16

-0.6

1, P

<0.0

01)

4)

69[

45(1

7%)

24(3

2%)]

5) IF

N(

0.54

, 95

%C

I: 0.

33-0

.89,

P=0

.02)

SVR

(0.

05, 9

5%C

I: 0.

006-

0.34

, P=0

.003

)

1)

IFN

SVR

2) IF

N

947

Yu

ML,

et

al.

A sust

aine

d vi

rolo

gica

l re

spon

se to

in

terfe

ron

or

inte

rfero

n/r

ibav

irin

redu

ces

hepa

toce

llula

r ca

rcin

oma

and

impr

oves

su

rviv

al in

ch

roni

c he

patit

is C

: a na

tionw

ide,

m

ultic

entre

st

udy

in

Taiw

an.

2006

(IFN

)

IFN

+

(RB

V)

1,06

5

565

:39

.5%

46.9

±11.

49 :38

.3%

43.6

±14.

0

: C :B

HIV

():

5.18

(1.0

-15

.3)

5.15

(1-1

6)

(HC

C)

1) H

CC

51(1

2.2%

)54

(35.

2%)

(P=0

.001

3)2)

HC

C0.

95%

1.92

%

3)

16(1

.5%

)12

(2.1

%)

SVR

()0

.4%

Non

-SV

R3.

2%(P

=0.0

22)

1.8%

(P<0

.000

1)4)

96

.2%

93.1

%(P

=0.3

928)

1) IF

NIF

N+R

BV

SVR

2)

3)

4) IF

NIF

N+R

BV

IFN

+RB

V

168

No

CQ

957

Iked

a K

, et

al.

Nec

essi

ties o

f in

terfe

ron

ther

apy

in

elde

rly

patie

nts

with

ch

roni

c he

patit

is

C.

2009

[

(IFN

)

(HC

C)

]

IFN

IFN

+

(RB

V)

: 454

(23.

7%)

1,91

7[ 45

4(IF

N 413

RB

V 41 )

1,46

3]

:21

424

0 6

2(6

0-80

) :66

080

3 65

(60-

88)

: 60

HC

V(H

CV

HC

V-R

NA

HB

V) :

6

HC

C

1) H

CC

10.8

%(4

9/4

54)

19.5

%(2

85/1

,463

)IF

N0.

67(P

=0.0

45)

2)

/5

97.

5% /

93.2

%10

89.

9% /

70.8

%15

64.

9% /

41.2

%(P

=0.0

001)

3)

ALT

HC

VC

ox(H

R)

HC

C<1

50,0

00/

3

IFN

(HR

: 0.5

6, P

=0.0

35)

150,

000/

3

: IFN

39

10(2

5.6%

)10

(25.

6%)

6(1

5.4%

)4

(10.

3%)

9(2

3.1%

)

1)

2)

2.6%

11.3

%(P

<0.0

01)

3)

IFN

53.8

%(1

86/3

46)

IFN

+RB

VIF

N

967

Gra

men

zi A

, et

al.

Impa

ct o

f in

terfe

ron

ther

apy

on

the

natu

ral

hist

ory

of

hepa

titis

C

viru

s re

late

d ci

rrhos

is.

2001

(IFN

)

3/ 3

3

36

9MU

72 72

( ) 1

:33

/39

:57

. 958

.1C

hild

-Pug

h(A

/B):

60/1

2

: 199

25

~199

45

IFN

: 5C

hild

-Pu

gh:

ALT

HC

VH

Bs

HIV

()

(HC

C)

():

55(2

-70

)58

(27-

71)

HC

C (

)

1)

7(1

0%)

9(1

2.5%

)2

2)

48(1

3-60

)52

(37-

60)

3) H

CC

619

25

HC

C1.

5% /

11%

11%

/ 27

%2

5(P

=0.0

006,

P=0

.013

)4)

IF

N

1) IF

N

2) A

FP20

ng/m

LH

CC

17%

66%

169

No

CQ

977

Soga

K

, et

al.

Effe

ct o

f in

terf

eron

on in

cide

nce

of

hepa

toce

llul

ar

carc

inom

a in

pat

ient

s w

ith

chro

nic

hepa

titis

C.

2005

()

reco

mbi

nan

t(

)

2a reco

mbi

n

2bIF

N

103

30

1

:50

5352

.2±1

4.0 :

1317

53.5

±11.

7

: C : B (HC

C)

1992

1~1

996

720

018

: 7.8

±1.8

HC

C5

HC

C5

(4.9

%)

7(2

3.3%

)(P

<0.0

1)

1) 2)IF

N

987

Iked

a K

, et

al.

Effe

ct o

f in

terf

eron

th

erap

y on

he

pato

cellu

lar

ca

rcin

ogen

esi

s in

patie

nts

with

ch

roni

c he

patit

is

type

C: A

lo

ng-te

rm

obse

rvat

ion

stud

y of

1,

643

patie

nts

usin

g st

atis

tical

bi

as

corr

ectio

n w

ith

prop

ortio

nal

haza

rd

anal

ysis

.

1999

733

(61.

5%)

6,00

0,00

0~9

,000

,00

0 IFN

8 2~3

16

RIA

ELIS

A

1,64

3( 1,

191

452

)

(A

): 80

238

950

(15-

86) (

B):

280

172

53(2

1-78

) :(

P<0

.000

1)( P=

0.04

0)(

P=0

.016

)(

P=0.

0001

6)A

LT(

P=0

.000

1)(

P=0.

0050

)IC

G

R15

(P=

0.00

17)

HC

V(g

enot

ype

1a1b

P=0.

0028

)H

CV

(P<

0.00

01) (

F1 P

=0.0

015)

: 197

4~19

95C

: HBs

HC

C(

): 5.

1(0

.1-1

1.3

)8.

2(0

.5-2

2.8

):

5255

HC

C :C

T

1) IF

N12

CR

(com

plet

e re

spon

se)=

HC

V-R

NA

461

(38.

7%)

IR(in

com

plet

e re

spon

se)=

HC

V-R

NA

ALT

-nor

mal

(6)1

45(1

2.2%

)N

R=n

o re

spon

se58

5(4

9.1%

)2)

HC

C:

25(2

.5%

)67

(14.

8%)

(P=0

.02)

HC

C: 5

2.1%

/ 4.

8%10

7.6%

/ 12

.4%

(P=0

.036

)C

RIR

3) C

R+I

R/N

R/

HC

C: 5

1.5

% /

2.7%

/ 4.

8%10

1.5

% /

14.9

% /

12.4

% (P

=0.0

011)

4)H

CC

5) C

ox4

IFN

HC

CIF

NC

RIR

[0

.32(

95%

CI:

0.13

-0.7

8)]

6):

6 /

355

: 99.

6% /

98.1

%10

: 98.

8% /

95.6

%(P

<0.0

01)

: 28

(2.4

%)

IFN

22(1

.8%

)9

(0.8

%)

5(0

.4%

)5

(0.4

%)

5(0

.4%

)(

)4(0

.3%

)13

(1.1

%)

[63

(5.3

%)]

1) I

FNC

RIR

2)C

RIR

3) I F

N

4)H

CC

170

No

CQ

997

Inou

e A

, et

al.

Effe

ctiv

enes

s of

inte

rfero

n th

erap

y fo

r re

duci

ng

the

inci

denc

e of

he

pato

cell

ular

ca

rcin

oma

amon

g pa

tient

s w

ith ty

pe

C c

hron

ic

hepa

titis

.

2000

(IFN

)

923

( 224 69

9

:70

.1%

645.

8%:

56.1

%64

24.6

%

1987

5~1

995

3H

CV

HB

s:

54.9

70.4

: HC

C19

9712

(HC

C)

1) H

CC

2.2%

9.5%

(P=0

.001

5)2)

4

(1.8

%)

84(1

2.0%

)3)

HC

C0

34

4) 5

HC

C2.

2%(9

5%C

I: 0-

4.4)

9.5%

(95%

CI:

7.1-

11.9

)(P

=0.0

015)

5) IF

NH

CC

69%

(HR

: 0.

31, 9

5%C

I: 0.

12-0

.80)

6) H

CC

0.82

(95%

CI:

0.18

-3.7

1)

1)

ALT

2)

3)

4)

5) IF

N

100

7

Di

Bis

ceg

lie

AM

, et

al;

HA

LT-

C

Tria

l In

ves

tigat

ors.

Prol

onge

d th

erap

y of

ad

vanc

ed

chro

nic

hepa

titis

C

with

low

-do

se

pegi

nter

fer

on.

2008

()

(PEG

-

3.5

1,05

0( 51

7 533

) :

10

( 517

): 30

.0%

51.1

±7.3 n

o re

spon

se 3

0.2%

(533

): 30

.8%

50.1

±7.0 n

o re

spon

se 3

0.8%

HC

V

geno

type

(P=0

.02)

:1=

95.2

%2=

1.2%

3=2.

1%4

or

6=1.

6%:

1=91

.6%

2=2.

8%3=

4.1%

4 or

6=

1.5%

: 2429

8SV

R(

)

237

:C

IFN

: 200

0~20

04: 1

,400

1)

1,40

034

.1%

(95%

CI:

29.8

-38.

5)33

.8%

(95%

CI:

29.4

-38

.1)

1.01

(95%

CI:

0.81

-1.2

7)

2)

38.6

%31

.8%

(P=0

.07)

IFN

C

171

No

CQ

101

7

Kas

aha

ra

A, e

t al

.

Inte

rfero

n tre

atm

ent

impr

oves

su

rviv

al in

ch

roni

c he

patit

is C

pa

tient

s sh

owin

g bi

oche

mic

al a

s wel

l as

vi

rolo

gica

l re

spon

ses

by

prev

entin

g liv

er-

rela

ted

deat

h.

2004

(IFN

)

2,69

8

256

)

:1,

738

960

53:

157

99 54

C IFN

3~6

162

512

:5.

88.

0

1)

SMR

(sta

ndar

dize

d m

orta

lity

ratio

: )

0.9(

95%

CI:

0.7-

1.1)

2.7(

95%

CI:

2.0-

3.0)

2)

SMR

5.5(

95%

CI:

4.3-

6.9)

22.2

(95%

CI:

16.0

-30.

0)

1) IF

N

2)

102

7B

run

o S,

et

al.

Pred

ictin

g m

orta

lity

risk

in

patie

nts

with

co

mpe

nsat

ed H

CV

-in

duce

d ci

rrhos

is: a

lo

ng-te

rm

pros

pect

ive

stud

y.

2009

(IFN

)

)

2003 IF

N+

352

( 194 15

8)

(

)

1989

~199

2 3

59(2

1-70

)51

(15.

6%)

: HC

V(

): 7

1C

hild

-Pug

hC

(HC

C) H

BV

HIV

():

14.4

(0.9

-19.

5)

Chi

ld-

Pugh

B HC

C

1)

(SV

R:

)28

HC

C7

(25.

0%)

4(1

4.3%

)(N

on-S

VR

)166

HC

C49

(29.

5%)

46(2

7.7%

)15

8H

CC

53(3

3.5%

)60

(38.

0%)

2)

(HR

: 2.

27, 9

5%C

I: 1.

41-3

.66)

3) M

ELD

(mod

el fo

r end

-sta

ge li

ver d

isea

se)

112.

15(9

5%C

I: 1.

50-3

.09)

1)

20%

2)

(Non

-SV

R)

3) M

ELD

10

172

CQ

8

No

CQ

103

8Fa

rtoux

L,

et a

l.

Effe

ct o

f pr

olon

ged

inte

rfer

on

ther

apy

on

the

outc

ome

of h

epat

itis

C v

irus-

rela

ted

cirr

hosi

s: a

rand

omiz

ed

trial

.

2007

()

C

(IFN

)

PCR

HC

V-R

NA

102

-2a

3,00

0,00

0 32

51

51

10

2328

60.5

IFN

:23

28 60.5

(SD

: 9.

7: 3

5-75

):

2328 60

.5(S

D:

9.4

: 31-

75)

:10

(1)

18~7

5 (2

) (3

)2

(4)P

CR

HC

V- R

NA

(5)

(6)

(7)

AFP

(HC

C)

(8)H

Bs

(9)

(10)

HIV

(11)

(12)

1

: 56

<80%

<35g

/L<1

30,0

00/m

LA

FP>2

0ng/

mL<

50ng

/mL

: AFP

>50n

g/m

LH

BV

HIV

>40g

/

32

(A

FP)

624

: 199

91

~200

210

SDS

inde

x (Z

ung

Self-

Rat

ing

Dep

ress

ion

Scal

e)

( <

50 5

0~59

60~

69 70)

1)2

24.5

%H

CC

12H

CC

13H

CC

2)IF

N98

%(1

2)

72.3

%(2

4)

90%

(12

)70

.7%

(24

)(P

=0.5

9)3)

IFN

17.1

13.6

(P=0

.2)

4) IF

NC

5) IF

NH

CV

-RN

A2

6): I

FN51

26(9

)(1

7)

IFN

1) C

IFN

2

2) 2

HC

C

IFN

HC

V

HC

V

3)

2H

CC

104

8A

rase

Y

, et

al.

Prol

onge

d-in

terf

eron

th

erap

y re

duce

s he

pato

carc

ino

gene

sis i

n ag

ed-

patie

nts

with

ch

roni

c he

patit

is C

.

2007

(IFN

)

+

(IFN

+RBV

)

120

240

:19

91~2

006

C

IFN 60

: 60

C

IFN

1991

4~2

006

3IF

NIF

N+R

BV4,

250

720

IFN

160

HC

V-R

NA

ALT

61.

5

12H

Bs

IFN

>2,5

00/

3

>70,

000/

3<2

.0

mg/

mL

CT

(HC

C) 12

03,

000,

000

2~3

2.47

IFN

SDS

inde

x (Z

ung

Self-

Rat

ing

Dep

ress

ion

Scal

e)

( <

50 5

0~59

60~

69 70)

1) H

CC

IFN

4IF

N38

2) 5

/10

HC

C5.

9% /

13.7

% 1

7.1%

/ 32

.8%

3) H

CC

AFP

>10n

g/m

LIF

N

4) IF

NH

CC

0.3

HC

C3.

9

60IF

NH

CC

173

No

CQ

105

8

Kos

kin

as

J, et

al

.

Ass

essm

ent o

f de

pres

sion

in

pat

ient

s w

ith

chro

nic

hepa

titis

: ef

fect

of

inte

rfero

n tre

atm

ent.

2002

(IFN

)(

)

132

Hip

pok

rat

ion

Hos

pita

l

C(H

CV

)38

(26 12

43)

B(H

BV

)36

(29 7

51)

58(

24 3457

)

(20

)

<10g

/

SDS

inde

x (Z

ung

Self-

Rat

ing

Dep

ress

ion

Scal

e)

( <

50

50~5

9

60~6

9 70)

1)

SDS

inde

xH

CV

34.4

(: 2

6.3-

67.5

)H

BV

40.0

(: 2

7.5-

61.3

)35

.6 (

:27

.5-6

1.3)

HC

VH

BV

(P=0

.01)

2)

HB

VH

CV

SDS

inde

xH

BV

HC

V(P

=0.0

01)

3)

SDS

inde

x

4)

SDS

inde

x(P

=0.0

08)

5)

SDS

inde

x

6)

:SD

S in

dex

70H

BV

2.8%

HC

V21

%5.

5%31

.6%

7)

1) IF

N

2)

106

8K

and

a Y

, et

al.

Inte

rfero

n-in

duce

d su

dden

he

arin

g lo

ss.

1995

1)

( 3 )2) (IF

N)

( 73)

2) IF

N

1) 3

2) 7

3

1)

57 55 62

2) 32

(21 11

):

25~6

3

1) C

IFN

32)

BC

73 (

1)

2) IF

N 20dB

1) 3

C2

IFN

1IF

N2)

73

32: 1

7/3

5(4

8.6%

): 1

5/3

8(3

9.5%

)]17

(23.

2%)

27(3

6.9%

)

176.

9MU

IFN

IFN

7~14

:43

.8%

IFN

174

No

CQ

107

8

Del

M

ont

e P,

et

al.

Endo

crin

e ev

alua

tion

in p

atie

nts

treat

ed

with

in

terfe

ron-

alph

a fo

r ch

roni

c he

patit

is

C.

1995

(IFN

)IF

N

3 6

31 C

IFN

(

)

18(2

4~48

)13

(26~

60)

CIF

N

:

IFN 3

6

1)

T4IF

N3

6(P

<0.0

5)2)

T3

3) T

SHTR

H6

4)

45)

6) IG

F-I

IGF-

IA

LT

IFN

108

8H

o SB

, et

al.

Influ

ence

of

ps

ychi

atric

di

agno

ses

on

inte

rfero

n-

treat

men

t fo

r chr

onic

he

patit

is C

in

a

vete

ran

popu

latio

n.

2001

12(

6

)

3332 1

C

CIF

N(6

8% >

29%

)(P

=0.0

24)

1)

2) (

:

)

3)

4)

175

No

CQ

109

8

Mar

tín

-Sa

ntos

R,

et a

l.

De

novo

de

pres

sion

an

d an

xiet

y di

sord

ers

and

influ

ence

on

ad

here

nce

durin

g pe

gint

erfe

ron

-alp

ha-

2a a

nd

ribav

irin

treat

men

t in

pat

ient

s w

ith

hepa

titis

C

.

2008

DSM

-IV

Axi

s I

diso

rder

s

(SC

ID-I)

Patie

nt

Hea

lth

Que

stio

nnai

re

(PH

Q)

Hos

pita

l A

nxie

ty a

nd

Dep

ress

ion

Scal

e (H

AD

S)

(IFN

)

176 30 14

6

(

)

119

57 45(S

D: 1

)

C24

: 200

41

~200

59

2ac

ute-

care

teac

hing

hos

ptia

l

)(

800~

1,20

0mg

)C

(HC

V24

48)

412

24PH

QH

AD

S:

HB

VH

IVA

FP

6

( )

1)

53/1

46(3

6%)

2)

27.8

(95%

CI:

2.82

-333

)3.

1 (1

.40-

7.03

) 3

.2(1

.12-

9.47

)IF

N+

3)

79%

90%

(P=0

.04)

4)

:(3

6%)

1)

2) IF

N

110

8G

lue

P, e

t al

.

A d

ose-

rang

ing

stud

y of

pe

gyla

ted

inte

rfero

n al

fa-2

b an

d rib

aviri

n in

chr

onic

he

patit

is

C. T

he

Hep

atiti

s C In

terv

entio

n Th

erap

y G

roup

.

2000

(PEG

-

(RB

V)

72

35 37

39.8

(:

20-6

8)

65.6

kg

ALT

CSV

R(

)1)

0

2)

03)

SV

R 2

3% (1

1/4

8)

1)

2)

PEG

-IFN

RB

V

176

No

CQ

111

8M

ann

s MP,

et

al.

Pegi

nter

fero

n al

fa-2

b pl

us

ribav

irin

com

pare

d w

ith

inte

rfer

on

alfa

-2b

plus

rib

aviri

n fo

r in

itial

tre

atm

ent o

f ch

roni

c he

patit

is C

: a ra

ndom

ised

tri

al.

2001

(PEG

-IFN

)

(RBV

)

1,53

0[H

ighe

r-dos

e PE

G-

IFN

+RBV

(Hig

h PE

G)

511

Low

er-d

ose

PEG

-IF

N+R

BV(L

ow P

EG)

514

IFN

+RBV

(IFN

) 505

]

/:

Hig

h PE

G32

1/1

90Lo

w P

EG 3

46/1

68IF

N33

6/1

69:

Hig

h PE

G43

Low

PEG

44IF

N43

:H

igh

PEG

82kg

Low

PE

G83

kgIF

N82

kg

ALT

CSV

R(

)

1)+R

BV

2)0

3)0

4) S

VR

: Hig

h PE

G54

%(2

74/5

11)

Low

PEG

47%

(244

/514

)IF

N47

%(2

35/5

05)

1) 2) PEG

112

8Fr

ied

MW

, et

al.

Pegi

nter

fero

n al

fa-2

a pl

us

ribav

irin

for

chro

nic

hepa

titis

C

viru

s in

fect

ion.

2002

(PEG

-IFN

)

(RBV

)

1,12

1

2a+R

BV(P

EG

+RBV

)453

2b+R

BV(IF

N+R

BV)4

44

2a+ (P

EG+

)224

]

81

/:

PEG

+RBV

324

/129

IFN

+RBV

325

/119

PEG

+ 1

51/7

3

:PE

G+R

BV42

.8IF

N+R

BV42

.3PE

G+

42.4 :

PEG

+RBV

79.8

kgIF

N+R

BV78

.4kg

PEG

+79

.1kg

ALT

C

:IF

N

AL T

6

144

(13%

):

HIV

1.5

1

: 199

92

~200

14

:24

SVR

()

1)2

(1

1)

0SV

R 5

6.3%

(255

/453

)2)

23

HC

VPE

G+R

BVIF

N+R

BVSV

R(7

6% v

s. 61

%, P

=0.0

05)

1H

CV

HC

V-R

NA

(2,0

00,0

00co

pies

/mL

)SV

RPE

G+R

BV41

%IF

N+R

BV33

%PE

G+

13%

SVR

PEG

+RBV

43%

IFN

+RBV

33%

PEG

+RBV

1(

3.25

, 95%

CI:

2.09

-5.1

2)40

(2.

60, 9

5%C

I: 1.

72-3

.95)

75kg

(1.

91, 9

5%C

I: 1.

27-2

.89)

SVR

(VR

)(H

CV

-R

NA

2log

HC

V-R

NA

)PE

G+R

BV86

%12

VR

12 12H

CV

-RN

AH

CV

-RN

A2l

ogSV

RV

R61

SVR

3):

PEG

+RBV

(3%

/ 7%

)PE

G+

(1%

/ 6%

)IF

N+R

BV(1

% /

10%

)(

)I F

N+R

BVPE

G+R

BVPE

G+

IFN

+RBV

(22%

vs.

20%

vs.

30%

)

177

No

CQ

113

8

Bos

que

s-Pa

dil

la F

, et

al.

Pegi

nter

fer

on a

lfa-2

a pl

us

ribav

irin

for

treat

ing

chro

nic

hepa

titis

C

viru

s in

fect

ion:

an

alys

is o

f M

exic

an

patie

nts

incl

uded

in

a

mul

ticen

ter in

tern

atio

nal

clin

ical

tri

al.

2003

(PEG

-

(RB

V)

32[P

EG-

2a+R

BV

(PEG

+RB

V)1

4

2b+R

BV

(IFN

+RB

V)1

2

2a+ (P

EG+

)6]

/:

PEG

+RB

V6

/8IF

N+R

BV

5/7

PEG

+ 2/4 :

PEG

+RB

V46 IF

N+R

BV

45PE

G+

45:

PEG

+RB

V75

kgIF

N+R

BV

68kg

PEG

+

81kg

ALT

C

: 199

92

~200

14

SVR

()

1)

02)

0

3) S

VR

: PEG

+RB

V50

%(7

/14

)IF

N+R

BV

33.3

%(4

/12

)PE

G+

0%(0

/6)

1)

2)

IFN

+RB

V1

114

8

Alfa

leh

FZ

, et

al.

Pegi

nter

fer

on a

lpha

-2b

plu

s rib

aviri

n co

mpa

red

with

in

terfe

ron

alph

a-2b

pl

us

ribav

irin

for i

nitia

l tre

atm

ent

of c

hron

ic

hepa

titis

C

in S

audi

pa

tient

s co

mm

only

in

fect

ed

with

ge

noty

pe

4.

2004

(PEG

-

(RB

V)

96[P

EG-

2b+R

BV

48

2b+ R

BV

48]

/:

2b+R

BV

22

/26

2b+R

BV

32

/16

:

2b+R

BV

48.4

2b+R

BV

45.2

BM

I: PE

G-

2b+R

BV

28.7

2b+R

BV

28.4

ALT

C(4

): 2

001

6~10

SVR

()

1)

02)

0

3) S

VR

43.

8% (2

1/4

8)

1(

)

178

No

CQ

115

8B

run

o S,

et

al.

Pegi

nter

fer

on a

lfa-2

b pl

us

ribav

irin

for n

aïve

pa

tient

s w

ith

geno

type

1

chro

nic

hepa

titis

C

: a

rand

omiz

ed co

ntro

lled

trial

.

2004

(PEG

-

(RB

V)

311

[

2b+R

BV

163 2b

+RB

V14

8]

: PEG

-

2b+R

BV

101

(62%

)

2b+R

BV

93(6

2%)

:

2b+R

BV

49.9

1 2b+R

BV

49.5

1:

2b+R

BV

69.4

1kg

2b+R

BV

71.5

6kg

ALT

C(1

): 2

000

1~6

SVR

()

1)

02)

0

3) S

VR

(P=0

.030

)41

.1%

(67

/163

)29

.7%

(44

/ 148

)

1)

24

77(2

4.8%

)2)

PE

G-IF

N IFN

(22%

vs.

11%

)3)

116

8

Had

ziy

anni

s SJ

, et

al;

PEG

ASY

S Inte

rna

tiona

l St

udy G

rou

p.

Pegi

nter

fer

on-

alph

a2a

and

ribav

irin

com

bina

tion

ther

apy

in c

hron

ic

hepa

titis

C

: a

rand

omiz

ed

stud

y of

tre

atm

ent

dura

tion

and

ribav

irin

dose

.

2004

(PEG

-

2448

(RB

V)

(800

mg/

) (1,0

00

1,20

0mg/

)

1,31

1

:99

838

42. 3

77.3

kgH

CV

-R

NA

2,00

0co

pies

/mL ALT

ALT

C

: AB

HIV

130g

/L12

0g/L

1.5

: 199

911

~200

21

:12

~24

SVR

()

1)

4(

2)

103

SVR

56%

(720

/1,2

84)

2) H

CV

148

3) H

CV

23

2a+R

BV

244)

48

24SV

R(P

=0.0

02)

5) R

BV

SVR

(P=0

.01)

6)

:

:

179

No

CQ

117

8H

asan

F,

et

al.

Pegi

nter

fero

n al

pha-

2b

plus

rib

aviri

n w

ith o

r w

ithou

t am

anta

dine

[c

orre

ctio

n of am

antid

ine]

fo

r the

tre

atm

ent o

f no

n-re

spon

ders

to

stan

dard

in

terf

eron

an

d rib

aviri

n.

2004

(PEG

-IFN

)

(RBV

)

63[

2b+R

BV21 PE

G-

2b+R

BV+A

MA

42]

: PEG

-

2b+R

BV16

(76%

)PE

G-

2b+R

BV+A

MA

34(8

0%)

:

2b+R

BV43

2b+R

BV+A

MA

42:

ALT

C

SVR

()

1)0

2)0

3) S

VR

: 4.

8%(1

/21

)7%

(3/4

2)

1) 2) 80%

3) AM

A

AM

A

118

8

Shiff

man

M

L,

et a

l; H

epat

itis C

A

ntiv

iral

Long

-Te

rm

Trea

tm

ent

Aga

inst

C

irrh

osis

Tr

ial

Gro

up.

Pegi

nter

fero

n al

fa-2

a an

d rib

aviri

n in

pa

tient

s w

ith

chro

nic

hepa

titis

C

who

hav

e fa

iled

prio

r tre

atm

ent.

2004

(PEG

-IFN

)

)

(RBV

)(75

kg1,

000m

g/75

kg1,

200m

g/)

604

35

20 HC

V-R

NA

438

49.9

89.2

kgH

epat

itis C

A

ntiv

iral

L ong

-term

Tr

eatm

ent

agai

nst

Cirr

hosi

s (H

ALT

-C)

IFN

:10

HC

VH

CV

-RN

A1

Isha

k3-

6IF

N4

12H

CV

-RN

A

:

3+2+

Chi

ld-T

urco

tte

Pugh

6

HIV 1.

5L <1

0g/d

L: H

ALT

-C20

018~

12:

24

20H

CV

-R

NA (V

R)

(EV

R)

122l

ogH

CV

-RN

A

(EO

T)48

HC

V-R

NA

(SV

R)

HC

V-R

NA

72( 24

)

1)0

0SV

R 1

8%(1

09/6

04)

2)20

5.6%

2060

%H

CV

-RN

A21

0(3

5%)

2018

24H

CV

-RN

A19

2(3

2%)

EOT

IFN

RBV

VR

78(4

1%)

572

SVR

109

(18%

)SV

RIF

N2

3A

ST/A

LTR

BV20

80%

60%

SVR

21%

11%

(P<0

.05)

HC

V-R

NA

20IF

NR

BVSV

R3)

: 16

573

IFN

84(1

5%)

RBV

103

(18%

)12

2(2

1%)

RBV

7%IF

N0.

3%3%

CBC

HC

V-R

NA

180

No

CQ

119

8

Zeuz

em

S,

et a

l; PE

GA

SYS St

udy

NR

1607

1In

vest

igat

or

Gro

up.

Pegi

nter

fero

n al

fa-2

a (4

0ki

loda

ltons

) an

d rib

aviri

n in

pa

tient

s w

ith

chro

nic

hepa

titis

C

and

norm

al

amin

otra

nsf

eras

e le

vels

.

2004

(PEG

-IFN

)

(RBV

) 80

0mg/

24(2

12:

A)

48(2

10: B

)(6

9)

3:3:

1

(11

)

491

:70

198

43.4

73.4

kg18

%2 9.

5%3~

4

1.4

ALT

C: 1

8H

CV

HC

V-

RN

AC

ALT

(34

142

26~

18)

ALT

30IU

/L

ALT

36Is

hak

:

(1,5

00/

3)

(90,

000/

3)

(Hb

:12

g/dL

13g/

dL)

HIV

HB

VH

AV

1.5

()

1

62

: 200

08

~200

34

:72

AB

24

SVR

(

)

SVR

1)1

(0

)13

SVR

40

.8%

(172

/422

)2)

SV

R24

4830

%52

%(

1.7,

95%

CI:

1.4-

2.2,

P<0

.001

)H

CV

1SV

R48

40%

2413

%(

3.1,

95%

CI:

1.9-

4.9,

P<0

.001

)2

3SV

R4

SVR

1(2

413

%48

56%

)1

4SV

R(1

2416

%9%

4847

%27

%4

2417

%0%

4867

%33

%)

23

2448

3):

77%

2448

(24

7%48

18%

)24

2%48

3%1

76%

ALT

(30~

59IU

/L60

~149

IU/L

150I

U/L

)24

40%

14%

2%48

38%

11%

1%45

%6%

1%

1) 2)69

()

120

8

Her

rine

SK

, et

al.

Pegi

nter

fero

n al

pha-

2a

com

bina

tion

ther

apie

s in

chro

nic

hepa

titis

C

patie

nts w

ho

rela

psed

afte

r or

had

a v

iral

brea

kthr

ough

on

ther

apy

with

stan

dard

in

terf

eron

al

pha-

2b p

lus

ribav

irin:

a

pilo

t stu

dy o

f ef

ficac

y an

d sa

fety

.

2005

(PEG

-IFN

)

(RBV

)

123

[

2a+R

BV32 PE

G-

(MM

F)29 PE

G-

(AM

A)3

1 PEG

-

+AM

A+R

BV

31]

/:

2a+R

BV 2

4/8

PEG

-

20/9

2a+A

MA

19

/12

2a+A

MA

+RB

V 2

0/1

1 :48

4846

46:

ALT

C

SVR

()

1)0

2):

13%

(4)

14%

(5)

16%

(5)

19%

(6)

3) S

VR

: 37

.5%

17%

10%

45%

1) 4(7

~19%

)2)

(48~

69%

)(4

7~61

%)

(35~

74%

)(1

9~52

%)

(32~

41%

)

3)19

4

181

No

CQ

121

8

Jaco

bson

IM

, et

al.

A rand

omiz

ed

trial

of

pegy

late

d in

terfe

ron

alph

a-2b

pl

us

ribav

irin

in th

e re

treat

men

t of

chro

nic

hepa

titis

C

.

2005

(PFG

-

(RB

V)

(A)P

EG-

+RB

V80

0mg/

(B)P

EG-IF

N

g/kg

/+R

BV

1,00

0~1

,200

mg/

321

(

)19

239

82

49.5

±7.4

ALT

C

: HB

s16

016

0

: 200

02

~200

13

:24

SVR

()

1)

031

SVR

15.

6%(5

0/3

21)

2) A

B3)

H

CV

-RN

A

(P=0

.002

)4)

1

(P=0

.01)

5) (P

=0.0

1)6)

7)

:

1) A

B

(8%

vs.

11%

, P=0

.45)

2)

24

122

8

Kam

al

SM,

et a

l.

Pegi

nter

fer

on

{alp

ha}-

2b a

nd

ribav

irin

ther

apy

in

chro

nic

hepa

titis

C

geno

type

4:

impa

ct

of

treat

men

t du

ratio

n an

d vi

ral

kine

tics o

n su

stai

ned

viro

logi

cal

resp

onse

.

2005

(PEG

-

(RB

V)

287

[(A

)PEG

-

2b+R

BV

24 9

5(B

)PEG

-

2b+R

BV

36 9

6(C

)PEG

-

2b+R

BV

48 9

6]

/:

(A)2

4 4

9/4

6(B

)36

51

/45

(C)4

8 5

0/4

6:

(A)2

4 4

1.6

(B)3

643

.9(C

)48

41.

2

ALT

C

: 200

21

~200

45

SVR

()

1)

02)

8

3) S

VR

: 54.

7% (1

57/2

87)

24 2

9%36

66%

48 6

9%

1) 3

48

2)

()

3)

182

No

CQ

123

8Le

e SD

, et

al.

Com

paris

on

of a

6-

mon

th

cour

se

pegi

nter

fer

on a

lpha

-2b

plu

s rib

aviri

n an

d in

terfe

ron

alph

a-2b

pl

us

ribav

irin

in tr

eatin

g C

hine

se

patie

nts

with

ch

roni

c he

patit

is C

in

Tai

wan

.

2005

(PEG

-

(RB

V)

153

-2b+

RB

V76

IFN

77]

/:

2b+R

BV

53

/23

2b+R

BV

52

/25

:

2b+R

BV

44.6

2b+R

BV

44.2 :

2b+R

BV

67.8

kg 2b+R

BV

66.2

kg

ALT

C

: 200

18

~200

212

SVR

()

1)

1(

0)

2)

53)

SV

R 6

7.1%

(51

/76

):

124

8Lo

dato

F,

et a

l.

Hig

her

dose

s of

pegi

nter

fer

on a

lpha

-2b ad

min

iste

red

twic

e w

eekl

y im

prov

e su

stai

ned

viro

logi

cal

resp

onse

in

diffi

cult-

to-

treat

pa

tient

s w

ith

chro

nic

hepa

titis

C:

resu

lts o

f a

pilo

t ra

ndom

ize

d st

udy.

2005

(PEG

-

(RB

V)

65 [(gr

oup

A)

122 (g

roup

B)

243

]

/:

(gro

up A

)1

12/1

0(g

roup

B)

223

/20

:(g

roup

A)

148

.7(g

roup

B

)2

49.6

:

ALT

C

: 200

111

~200

24

SVR

()

1)

02)

0

3) S

VR

: 52.

3% (3

4/6

5)

grou

p B

72%

vs.

grou

p A

25

% (P

=0.0

24)

1)

2)

grou

p A

32%

(7/2

2)

grou

p B

19

%(8

/43

)(

)3)

183

No

CQ

125

8M

ang

ia A

, et

al.

Pegi

nter

fero

n al

fa-2

b an

d rib

aviri

n fo

r 12

vs.

24

wee

ks in

H

CV

ge

noty

pe 2

or

3.

2005

(PEG

-IFN

)

(RBV

)

283

[sta

ndar

d-du

ratio

n( )

2b+R

BV 2

4)7

0va

riabl

e-du

ratio

n( )

2b+R

BV 1

224

)213

]

():

stan

dard

-dur

atio

n39

(56%

)va

riabl

e-du

ratio

n11

9(5

6%)

:st

anda

rd-d

urat

ion

49.7

varia

ble-

dura

tion

46.6

:st

anda

rd-d

urat

ion

69.5

kgva

riabl

e-du

ratio

n69

.4kg

ALT

C(2

3)

: 200

26

~200

41

SVR

()

1)0

2)0

3) S

VR

76.

7% (2

17/2

83)

1) 2

412

2)12

4%(6

)24

9%(1

4)

3)

126

8

von

Wag

ner

M,

et a

l.

Pegi

nter

fero

n-al

pha-

2a

(40K

D) a

nd

ribav

irin

for

16 o

r 24

wee

ks in

pa

tient

s w

ith

geno

type

2

or 3

chr

onic

he

patit

is C

.

2005

(PEG

-

(RB

V)

)R

BV

800

~1,2

00

mg/

(65

kg80

0mg

65~8

5kg

1,00

0mg

85kg

1,20

0mg)

4

HC

V-

RN

A60

0IU

/mL

(rap

id

viro

logi

cal

resp

onse

: RV

R)

8

16(A

)24

(B)

RV

R

24

(C)

153

[A71

B71

C11

]

63

/: A

52/1

9B

41/3

0C

4/7

: A38

B39

C42 : A

75.3

kgB

74.6

kgC

80.1

kg

ALT

C(2

3)

: 18

C(

23

)

RBV

HC

V-R

NA

600I

U/m

L18

ALT

12g/

dL13

g/dL

:H

IVH

BV

1

: 200

22

~200

43

:24

SVR

()

1)0

7SV

R 7

7.8%

(119

/153

)2)

411

RV

R(V

R)

88%

SVR

A82

%B

80%

97.5

%C

I11

.5%

RV

RC

SVR

36%

BV

RC

72%

B84

%2

SVR

92%

373

%3

800,

000I

U/m

LSV

R59

%80

0,00

0IU

/mL

85%

2A

BSV

R3

HC

V-R

NA

800,

000I

U/m

LA

B80

0,00

0IU

/mL

SVR

A67

%B

55%

(P>0

.2)

3): 7

(

)B

1A

1B

5C

216

24IF

NR

BV14

%11

% (3%

)(6

%)

IFN

184

No

CQ

127

8

Zeuz

em

S, e

t al

; D

ITT

O-

HC

V

Stud

y Gro

up.

Inte

rnat

ion

al,

mul

ticen

ter, ra

ndom

ize

d,

cont

rolle

d st

udy

com

parin

g dy

nam

ical

ly

indi

vidu

ali

zed

vers

us

stan

dard

tre

atm

ent

in p

atie

nts

with

ch

roni

c he

patit

is

C.

2005

(PEG

-

268

179

89 :41

.6±1

0.2 :

74.3

kg±

13.4

kg

ALT

C

: 200

12

~200

311

SVR

()

1)

02)

19

3) S

VR

: 60

%60

%

1)

2)

128

8

Abe

rge

l A

, et

al;

Fren

ch

mul

tice

nte

r stud

y gr

oup.

Pegi

nter

fer

on a

lpha

-2b

plu

s rib

aviri

n fo

r tre

atm

ent

of c

hron

ic

hepa

titis

C

with

seve

re

fibro

sis:

a

mul

ticen

tre

rand

omiz

ed co

ntro

lled

trial

co

mpa

ring

two

dose

s of

pe

gint

erfe

ron

alp

ha-

2b.

2006

(PEG

-

(RB

V)

203

[PEG

-

g/kg

/+R

BV

(800

mg/

)48

101 PE

G-

g/kg

/+R

BV

(800

mg/

)48

102

]

: PEG

-

+RBV

481.

8PE

G-

+RBV

482.

2:

g/kg

/+R

BV48

49.3

PEG

-

+RBV

4851

.1BM

I:

g/kg

/+R

BV48

25.9

PEG

-

+RBV

4825

.4

ALT

CSV

R(

)1)

2

2)

03)

SV

R 4

0.9%

(83

/203

)

:2

185

No

CQ

129

8B

erg

C, e

t al

.

Re-

treat

men

t of

chr

onic

he

patit

is C

pa

tient

s af

ter

rela

pse:

ef

ficac

y of

pe

gint

erfe

ron

-alp

ha-

2a (4

0 kD

a) a

nd

ribav

irin.

2006

64

51 1344

80kg

±15k

g

ALT

C

SVR

()

1)

02)

5

3) S

VR

54.

7% (3

5/6

4)

1)

(5%

)(3

%)

2)

130

8B

erg

T, e

t al

.

Exte

nded

tre

atm

ent

dura

tion

for

hepa

titis

C

viru

s typ

e 1:

co

mpa

ring

48 v

ersu

s 72

wee

ks

of

pegi

nter

fer

on-a

lfa-2

a pl

us

ribav

irin.

2006

(48

vs.

72)

455

250

205

42.7

±11

.44

75.8

kg ALT

2.52

±1.

63IU

/L(

)1b

ALT

C

:18

HC

V-

RN

A1,

000I

U/m

LA

LT 130g

/L12

0g/L

1.5m

g/dL :

1bB

HIV

: 200

012

~200

17

:24

SVR

()

1)

02)

61

(48

36

72 2

5)

3) S

VR

53.

2%(2

42/4

55) (

48 5

3%72

54%

)4)

(4

872

)

1)

(48

15.6

%72

11.1

%)

2)

186

No

CQ

131

8

Bra

ndã

o C

, et

al;

Pega

sys

Bra

zilia

n St

udy G

rou

p.

The

resu

lts

of a

ra

ndom

ize

d tri

al

look

ing

at

24 w

eeks

vs

48

wee

ks o

f tre

atm

ent

with

pe

gint

erfe

ron

alp

ha-2

a (4

0 kD

a)

and

ribav

irin

com

bina

tion

ther

apy

in p

atie

nts

with

ch

roni

c he

patit

is C

ge

noty

pe 1

.

2006

117

[(gr

oup

A) 1

24

:32 (g

roup

B) 1

48

:31 (g

roup

C)

1 2

4: 5

4]

/:

24 1

9/1

348

19/1

21

2446

/8:

24 4

1.1

4840

.81

24 4

2.3 :

24 73.8

kg48

76.

4kg

124

80.7

kg

ALT

C

: 200

13

~200

38

SVR

()

1)

02)

6

3) S

VR

: gro

up A

19%

grou

p B

48%

grou

p C

76%

3 ()

40%

132

8

Bro

now

icki

JP

, et

al.

Effe

ct o

f rib

aviri

n in

ge

noty

pe 1

pa

tient

s w

ith

hepa

titis

C

resp

ondi

ng

to

pegy

late

d in

terfe

ron

alfa

-2a

plus

rib

aviri

n.

2006

516

306

210

46.2

±11.

5

70.8

kg±

14.8

kg

ALT

C

: 200

012

18~2

003

49

SVR

()

1)

1(

0)

2)

433)

SV

R

1)

:1

2) A

rm1

RN

A

Arm

23

Arm

1

187

No

CQ

133

8

Cia

nci

o A

, et

al.

A rand

omiz

ed

trial

of

pegy

late

d-in

terf

eron

-al

pha2

a pl

us

ribav

irin

with

or

with

out

aman

tadi

ne

in th

e re

-tre

atm

ent o

f pa

tient

s w

ith

chro

nic

hepa

titis

C

not

resp

ondi

ng

to st

anda

rd

inte

rfer

on

and

ribav

irin.

2006

(PEG

-

(RB

V)+

(AM

A)

161

[PEG

-IF

N+R

BV

81 PE

G-

IFN

+RB

V+A

MA

80]

/:

PEG

-IF

N+R

BV

60

/21

PEG

-IF

N+R

BV

+AM

A 5

9/2

1 :PE

G-

IFN

+RB

V50

PEG

-IF

N+R

BV

+AM

A50 B

MI:

PEG

-IF

N+R

BV

24.

9PE

G-

IFN

+RB

V+A

MA

24.8

ALT

C: 2

001

5~2

002

12

SVR

()

1)

1(

)2)

4

3) S

VR

29.

6% (2

4/8

1)

:1

134

8

Fere

nci

P, e

t al

; A

ustr

ian

Hep

atit

is

Stud

y Gro

up.

Ran

dom

ize

d, d

oubl

e-bl

ind,

pl

aceb

o-co

ntro

lled

stud

y of

pe

gint

erfe

ron

alfa

-2a

(40K

D)

plus

rib

aviri

n w

ith o

r w

ithou

t am

anta

dine

in

tre

atm

ent-

naïv

e pa

tient

s w

ith

chro

nic

hepa

titis

C

geno

type

1

infe

ctio

n.

2006

(PEG

-

(RB

V)+

(AM

A)

209

[gro

up A

:

2a+R

BV

+A

MA

114

grou

p B

: PEG

-

2a+R

BV

+Pla

cebo

95]

/:

2a+R

BV+A

MA

68

/46

PEG

-IFN

2a+R

BV+P

lac

ebo

65/3

0 :

2a+R

BV+A

MA

45PE

G-

2a+R

BV+P

lac

ebo4

4 BMI:

2a+R

BV+A

MA

25.5

PEG

-

2a+R

BV+P

lac

ebo2

5.7

ALT

CSV

R(

)1)

0

2)

13)

SV

R: g

roup

A 4

6.5%

(53

/114

)gr

oup

B 5

1.6%

(49

/95

)

1) g

roup

A12

grou

p B

6

2) g

roup

A ()

3) g

roup

AQ

OL

188

No

CQ

135

8

Mey

er-

Wys

s B

, et

al;

Swis

s Ass

oci

ati

on

for

the

Stud

y of

th

e Li

ver

(SA

SL)

.

Com

paris

on

of tw

o PE

G-

inte

rfero

n al

pha-

2b

dose

s (1.

0 or

1.5

m

icro

g/kg

) com

bine

d w

ith

ribav

irin

in

inte

rfero

n-na

ïve

patie

nts

with

ch

roni

c he

patit

is C

an

d up

to

mod

erat

e fib

rosi

s.

2006

(PEG

-

(RB

V)

219

g/kg

+RB

V

113

g/kg

+RB

V

106

]

():

g/kg

+RB

V 6

4(5

7%)

g/kg

+RB

V 7

6(7

2%)

:

g/kg

+RB

V 3

9PE

G-IF

N

g/kg

+RB

V 4

2

:

g/kg

+RB

V

72kg

PEG

-

g/kg

+RB

V

73kg

ALT

C

: 200

011

~200

26

SVR

()

1)

1(

)2)

19

3) S

VR

53.

4% (1

17/2

19)

:1

136

8Y

eni

ce N

, et

al.

The

effic

acy

of

pegy

late

d in

terfe

ron

alph

a 2a

or

2b

plus

rib

aviri

n in

chr

onic

he

patit

is C

pa

tient

s.

2006

(PEG

-

-2b+

(RB

V)

74[

2a+R

BV

37

2b+R

BV

37]

/:

2a+R

BV

13

/24

PEG

-

2b+R

BV

10

/27

(/

):

2a+R

BV

48.

2/5

0.9

2b+R

BV

50.

8/5

0.85

:

ALT

C

SVR

()

1)

02)

0

3) S

VR

: 48

.6%

35.1

%

189

No

CQ

137

8Y

u M

L,

et a

l.

A rand

omiz

ed

trial

of

24- v

s. 48

-w

eek

cour

ses o

f PE

G

inte

rfero

n al

pha-

2b

plus

rib

aviri

n fo

r ge

noty

pe-

1b-

infe

cted

ch

roni

c he

patit

is C

pa

tient

s: a

pilo

t stu

dy

in T

aiw

an.

2006

(PEG

-

(RB

V)

60[P

EG-

2b+R

BV

24 4

5PE

G-

2b+R

BV

48 1

5]

/:

24 2

8/1

748

11

/4:

24 4

5.4

4845

.1:

24 68.3

kg48

68.

6kg

ALT

C(1

): 2

001

9~2

004

11

SVR

()

1)

02)

0

3) S

VR

: 24

48.

9%(2

2/4

5)

48 8

0%(1

2/1

5)

1)

2)

138

8

Zeuz

em

S, e

t al

.

Effic

acy

of 2

4 w

eeks

tre

atm

ent

with

pe

gint

erfe

ron

alfa

-2b

plus

rib

aviri

n in

pat

ient

s w

ith

chro

nic

hepa

titis

C

infe

cted

w

ith

geno

type

1

and

low

pr

etre

atm

ent

vire

mia

.

2006

237

127

110

42.2

(:

18-6

9)

71.3

kg(

:44

-111

kg)

ALT

CSV

R(

)1)

0

2)

25(1

1%)

3) S

VR

: 24

50%

(117

/ 235

)48

71%

(27

/38

)

190

No

CQ

139

8C

arr

C, e

t al

.

Effic

acy

of

inte

rfero

n al

pha-

2b

indu

ctio

n th

erap

y be

fore

re

treat

men

t for

ch

roni

c he

patit

is

C.

2007

+

stud

y 1:

48

4st

udy

2:

407

stud

y1: 4

84(

331

152

) 45.5

±8.1

stud

y2: 4

07(

297

110

) 48.2

±6.7

ALT

C

SVR

()

1)

02)

0

3) S

VR

: 20

%24

%

5%:

140

8D

iag

o M

, et

al.

Clin

ical

tri

al:

phar

mac

ody

nam

ics

and

phar

mac

oki

netic

s of

re-

treat

men

t w

ith fi

xed-

dose

in

duct

ion

of

pegi

nter

fer

on a

lpha

-2a

in

hepa

titis

C

viru

s ge

noty

pe 1

tru

e no

n-re

spon

der

patie

nts.

2007

(PEG

-

(RB

V)

72[

28

PEG

-

20

24

]

/: 21

/7PE

G-

g/ 1

5/5

PEG

-IFN

20/4

: 40.

0PE

G-IF

N

44.5

PEG

-

g/ 4

1.0

:

75.8

kgPE

G-

g/ 7

4.1k

g

79.0

kg

ALT

C(1

)

SVR

()

1)

02)

:

11%

5%4%

3) S

VR

: 18

%30

%38

%

3

191

No

CQ

141

8D

iag

o M

, et

al.

Trea

tmen

t of

chr

onic

he

patit

is C

ge

noty

pe 1

w

ith

pegi

nter

fer

on-a

lpha

2a

(40

kDa)

pl

us

ribav

irin

unde

r ro

utin

e cl

inic

al

prac

tice

in

Spai

n:

early

pr

edic

tion

of

sust

aine

d vi

rolo

gica

l re

spon

se

rate

.

2007

(PEG

-

(RB

V)

475

319

156

43.5

±10.

2

74.3

kg±

13.7

kg

C(1

): 2

002

5~2

005

5

SVR

()

1)

1(

)2)

SV

R 4

8% (9

5%C

I: 43

.3-5

2.3)

3)

6%(2

7:

)

1)

15%

[(5

1%)

(24%

)(2

4%)

(19%

)(1

9%)

(17%

)(1

7%)

(15%

)]2)

142

8

Kam

al

SM,

et a

l.

Pegy

late

d in

terfe

ron

alph

a-2b

pl

us

ribav

irin

in p

atie

nts

with

ge

noty

pe 4

ch

roni

c he

patit

is

C: T

he

role

of

rapi

d an

d ea

rly

viro

logi

c re

spon

se.

2007

(PEG

-

(RB

V)

358

[gro

up

A(P

EG-IF

N

24) 6

9gr

oup

B(P

EG-IF

N

36) 7

9gr

oup

C(P

EG-IF

N

48) 1

60

(PEG

-

2b+R

BV

48

) 50

]

():

grou

p A

(24

)37

(54%

)gr

oup

B(36

)32

(40%

)gr

oup

C(4

8)

100

(62%

) 2

6(5

2%)

:gr

oup

A 4

1.0

grou

p B

40.5

grou

p C

42.

2 43.

2BM

I: gr

oup

A

28.5

grou

p B

27.8

grou

p C

28

.628

.9

ALT

C(4

): 2

004

1~2

006

11

SVR

()

1)

02)

0

3) S

VR

66.

8%(2

39/3

58):

grou

p A

86%

(59

/69

)gr

oup

B 7

6%(6

0/7

9)

grou

p C

56%

(90

/160

) 6

0%(3

0/5

0)

192

No

CQ

143

8K

ubo

ki M

, et

al.

Pegi

nter

fer

on a

lpha

-2a

(40

KD

) plu

s rib

aviri

n fo

r the

tre

atm

ent

of c

hron

ic

hepa

titis

C

in

Japa

nese

pa

tient

s.

2007

(

)

(PEG

-

(RB

V)

1)

2a+R

BV

99

2)

2a 101

3)

2a+R

BV

100

43

1)

PEG

-IFN

:62 37

52.0

2)

PEG

-IFN :

62 3950

.6

3)

2a+R

BV

:74 26

52.0

20A

LTC

(1b

)

:H

BV

: 200

26

~200

49

SVR

()

SVR

RB

V61

%PE

G-IF

N26

%(P

<0.0

01)

IFN

SVR

51%

IFN

50%

(R

BV

)R

BV

19.8

%PE

G-IF

N15

.2% 18

.0%

RB

V1%

RB

V12

.9%

PEG

-IFN

11.1

%(R

BV

)9%

43

PEG

-IFN

RB

V

IFN

144

8

Mar

cel

lin

P, e

t al

.

Phas

e 2

stud

y of

th

e co

mbi

nati

on o

f m

erim

epo

dib

with

pe

gint

erfe

ron

-al

pha2

b,

and

ribav

irin

in

nonr

espo

nde

rs to

pr

evio

us

ther

apy

for

chro

nic

hepa

titis

C

.

2007

[ (MM

PD)

II]

(PEG

-

(RB

V)

( MM

PD

)

2b+R

BV

+ :10 2b

+RB

V+

MM

PD25

mg:

10

2b+R

BV

+M

MPD

50m

g: 1

1

(

8

5)

2b+R

BV

+ :8

51.4

75.8

kg

2b+R

BV

+MM

PD25

mg:

7

48.5

64.8

kg

2b+R

BV

+MM

PD50

mg:

3

48.4

72.0

kg

C (

1)

18~7

0 :

CR

BV

: 200

25

~200

41

SVR

()

SVR

30%

(3/1

0)

SVR

20%

(2/1

0)

SVR

73%

(8/1

1)

MM

PD

PEG

-

193

No

CQ

145

8

Pear

lm

an

BL,

et

al.

Trea

tmen

t ex

tens

ion

to 7

2 w

eeks

of

pegi

nter

fer

on a

nd

ribav

irin

in

hepa

titis

c

geno

type

1-

infe

cted

slo

w

resp

onde

rs.

2007

(

)

48(

A):

49 72(

B):

52

( )

HC

V-1

18

A:

33 5

6

BM

I 28.

8B

: 34

54

BM

I 29.

1

C(1

)A

LT18

24

: HIV

1H

CV

HB

V

2003

6~2

005

9

SVR

()

ASV

R9

/49

(18%

)B

SVR

20/5

2 (3

8%)

(P=0

.03)

A13

/22

(59%

)B

5/2

5(2

0%)

146

8

Shiff

man

M

L,

et a

l.

Trea

tmen

t of

chr

onic

he

patit

is C

vi

rus

geno

type

1

with

pe

gint

erfe

ron

, rib

aviri

n,

and

epoe

tin

alph

a.

2007

(

)

(PEG

-

(RB

V)+

(

)

2b+R

BV

(

)48 2b

+RB

V(

)+

49

2b+R

BV

( ) +

49

(

)

PEG

-IF

N+R

BV

: 56

%49

82kg

PEG

-IF

N+R

BV

+

63%

48

83kg

PEG

-IF

N+R

BV

() +

56%

45

82kg

C(1

):

HB

V1

HC

V HIV

Chi

ld-P

ugh

6

SVR

()

SVR

PEG

-IFN

+RB

V29

%PE

G-IF

N+R

BV

+19

%PE

G-IF

N+R

BV

() +

49%

(P<0

.05)

PE

G-IF

N+R

BV

36%

PEG

-IFN

+RB

V+

40%

PEG

-IFN

+RB

V(

) +8%

(P<0

.05)

PEG

-

SVR

RB

V

(R

BV

)

194

No

CQ

147

8

Sjog

ren

M

H,

et a

l.

Ant

ivira

l re

spon

se

of H

CV

ge

noty

pe 1

to

co

nsen

sus

inte

rfero

n an

d rib

aviri

n ve

rsus

pe

gyla

ted

inte

rfero

n an

d rib

aviri

n.

2007

(

)

(IFN

)+

(RB

V)

2b+R

BV

IFN

+RB

V

30 2b+R

BV 2

9

(

)

IFN

+RB

V:

70%

45

91kg

2bR

BV

:65

.5%

46

82kg

18C

(1)

:SV

R(

)

SVR

IFN

+RB

V11

/30

(37%

)12

/29

(41%

)(P

=0.7

92)

IFN

+RB

V10

%7%

IFN

+RB

V

148

8Y

u M

L,

et a

l.

A rand

omis

ed

stud

y of

pe

gint

erfe

ron

and

rib

aviri

n fo

r 16

vers

us 2

4 w

eeks

in

patie

nts

with

ge

noty

pe 2

ch

roni

c he

patit

is

C.

2007

(

)

(PEG

-

(RB

V)

( 1624

)

16 5

024

100

(12

)

(1

3 )

16:

32( 6

4%)

50.8

67.7

kg24

:58

(58%

)49

.9

65.8

kg

18~6

5A

LTC

(2)

:

2H

CV

HIV

(Chi

ld-P

ugh

BC

)

: 200

39

~200

512

SVR

()

SVR

2495

/ 100

(95%

95%

CI:

91-

99)

1647

/50

(94%

95%

CI:

87-1

00)

2424

3.1%

166%

C (2)

SVR

243.

1%16

6%

195

No

CQ

149

8

Ang

elic

o M

, et

al;

SMIE

C II

In

vest

igat

ors.

Pegi

nter

fero

n al

pha-

2a a

nd

ribav

irin

vers

us

pegi

nter

fero

n al

pha-

2a

mon

othe

rapy

in

ear

ly

viro

logi

cal

resp

onde

rs

and

pegi

nter

fero

n al

pha-

2a a

nd

ribav

irin

vers

us

pegi

nter

fero

n al

pha-

2a,

ribav

irin

and

aman

tadi

ne

tripl

e th

erap

y in

ear

ly

viro

logi

cal

nonr

espo

nder

s: th

e SM

IEC

II

trial

in n

aïve

pat

ient

s w

ith c

hron

ic

hepa

titis

C.

2008

( IIIb )

(PEG

-

(RB

V)

[12

PEG

-

12 (EV

R)

PEG

-

2a+R

BV

EVR

2a+R

BV

2a+R

BV

+

(AM

A)

]

210

EVR

121

2a 6

4PE

G-

2a+R

BV 5

7)

EVR

89

2a+R

BV 4

2

2a+R

BV+A

MA

47

)

(

12 )

230

:69

% 42BM

I 24.

6

18~6

5A

LTC

:(

)H

BVH

IV

2001

SVR

()

EVR

(121

/210

57.6

%)

SVR

38/6

4(5

9.3%

)38

/57

(67.

2%)

()

EVR

(89

/210

42.4

%)

SVR

7/4

2(1

6.7%

)2a

+RBV

+AM

A15

/47

(31.

9%)

(P=

0.07

)32

(13.

9%)

206

(1

21

11

)

HC

V1

4EV

RPE

G-

SVR

150

8

Bain

V

G,

et a

l; C

ana

dian

PE

GA

SYS St

udy

Gro

up.

Clin

ical

tri

al:

expo

sure

to

ribav

irin

pred

icts

EV

R a

nd

SVR

in

patie

nts

with

HC

V

geno

type

1

infe

ctio

n tre

ated

with

pe

gint

erfe

ron

alph

a-2a

pl

us

ribav

irin.

2008

(

)

(PEG

-IFN

)

(RBV

)

(RBV

800m

g/

1,00

0mg/

1,20

0mg/

)

RBV

800m

g/

339

RBV

1,00

01,

200m

g/ 552

RBV

800m

g/:

234

(69%

)45

81kg

RBV

1,00

01,

200m

g/:

382

(69%

) 47.1

80kg

C(1

) (

):

HC

V1

SVR

()

SVR

RBV

800m

g/15

2/3

39(4

5%)

RBV

1,00

01,

200m

g/29

7/5

52(5

4%)

RBV

(%)

SVR

1.26

(95%

CI:

1.14

-1.3

9, P

<0.0

01)

800m

g/ 1,00

01,

200m

g/

196

No

CQ

151

8

Lagg

ing

M, e

t al

; N

OR

Dyn

am

IC

Stud

y Gro

up.

Ran

dom

ized

co

mpa

riso

n of

12

or

24 w

eeks

of

pe

gint

erfe

ron

alp

ha-

2a a

nd

ribav

irin

in c

hron

ic

hepa

titis

C

viru

s ge

noty

pe

2/3

infe

ctio

n.

2008

( III)

12 194

24 188

(

)31

12:

123

(63%

)41

.5

79.8

kg24

:10

5(5

6%)

42.0

76.5

kg

18C

(23

) :2

3H

CV

HB

VH

IV

SVR

()

2SV

R12

56%

2482

%(P

=0.0

057)

3SV

R12

58%

2478

%(P

=0.0

015)

40

HC

V-R

NA

15IU

/mL

152

8N

apo

li N

, et

al.

The

use

of

diffe

rent

Pe

g-in

terfe

ron

alph

a-2b

re

gim

ens

plus

rib

aviri

n in

H

CV

-1b-

infe

cted

pa

tient

s af

ter r

apid

vi

rolo

gica

l re

spon

se

does

not

af

fect

the

achi

evem

ent

of

sust

aine

d vi

rolo

gica

l re

spon

se.

2008

(PEG

-

[4

(RV

R)

44PE

G-IF

N

2

]

44PE

G-

: 17

44PE

G-

: 14

:11

47.3

:10

46.9

45C

(1b

)R

VR

31:

HIV

6 SVR

()

6SV

R16

/17

(94.

1%)

13/1

4(9

2.8%

)(

)

RV

R

197

No

CQ

153

8

Rof

fi L,

et

al;

Gru

ppo

Ep

atol

ogi

co

Lom

bard

o.

Pegy

late

d in

terfe

ron-

alph

a2b

plus

rib

aviri

n:

an

effic

acio

us

and

wel

l-to

lera

ted

treat

men

t re

gim

en

for

patie

nts

with

he

patit

is C

vi

rus

rela

ted

hist

olog

ica

lly p

rove

n ci

rrhos

is.

2008

(

)

(PEG

-

(RB

V)

[ 2b+R

BV

2b+R

BV

]

2b+R

BV 5

7

IFN

36

( 10

)

2b+R

BV :

36 2156

75kg

158

%

2b+R

BV :

20 1655

. 5

72kg

178

%

65A

LTC

:

Chi

ld-

Pugh

BC

F2F3

HIV

HB

VH

CV : 2

002

1~2

003

12

SVR

()

SVR

25/5

7(4

4%)

12/3

6(3

3%)

(P=0

.31)

1SV

R(P

EG-IF

N24

% v

s. IF

N25

%, P

=0.9

4)2

SVR

(PEG

-IF

N80

% v

s. IF

N67

%, P

=0.5

2)3

SVR

(PEG

-IFN

56%

vs.

IFN

50%

, P=0

.89)

2b+R

BV

2b+R

BV

()

12

: 3

: 2

200

PEG

-IFN (

IFN

)

154

8Sc

ott

o G

, et

al.

Peg-

inte

rfero

n al

pha-

2a

vers

us

Peg-

inte

rfero

n al

pha-

2b

in

nonr

espo

nde

rs w

ith

HC

V

activ

e ch

roni

c he

patit

is: a

pi

lot

stud

y.

2008

(

)

(PEG

-

(RB

V)

PEG

-

2b+R

BV

2a+R

BV

71

2b+R

BV

72

2a+R

BV

: 42 29

45.8

6

80.7

kg

2b+R

BV

: 40 32

47.8

2

78.9

kg

(IF

N+R

BV

)A

LTC

: 6H

CV

HIV A

F P

: 200

111

~200

76

SVR

()

SVR

/71

(19.

7%)

PEG

-/7

2(1

8.0%

)

2a+R

BV

10(

)2a

+RB

V4

15%

1

2a+R

BV

PEG

-

IFN

+RB

V

PEG

-IFN

+RB

V20

%SV

R

198

No

CQ

155

8So

od

A, e

t al

.

Com

paris

on

of lo

w-

dose

pe

gyla

ted

inte

rfero

n ve

rsus

st

anda

rd

high

-dos

e pe

gyla

ted

inte

rfero

n in co

mbi

natio

n w

ith

ribav

irin

in

patie

nts

with

ch

roni

c he

patit

is C

w

ith

geno

type

3:

an In

dian

ex

perie

nce.

2008

(PEG

-

(RB

V)

2b

)

2b

)+R

BV

76 2b g/

kg/

)+R

BV

27

(

)

2b:

67 9

43.1

2.34

2b:

21 6

37.3

1.64

16~7

0A

LTC

(3)

: 3H

CV

HB

VH

IV

()

()

SVR

()

SVR

60/7

6(7

8.9%

)25

/27

(92.

6%)

(P=0

.145

)1

156

8Ta

ng

KH

, et

al.

Clin

ical

tri

al:

indi

vidu

ali

zed

treat

men

t du

ratio

n fo

r he

patit

is C

vi

rus

geno

type

1

with

pe

gint

erfe

ron

-alp

ha

2a p

lus

ribav

irin.

2008

1) 12 1224

36

2) 1

2 48

45 12

32

12 1124 10 36 11 12

13 48

(

)

89%

12:

47

4270

kg24

:5

538

69kg

36:

83

4179

kg (48

):

94

4171

kg

18~6

5C

(1)

: HB

VH

AV

HIV

12

312

SVR

()

12SV

R12

5/1

1(4

5%)

248

/10

(80%

)36

8/1

1(7

3%)

12SV

R4

/13

(31%

)

12

24

199

No

CQ

157

8

von

Wag

ner

M, e

t al

.

Plac

ebo-

cont

rolle

d tri

al o

f 40

0 m

g am

anta

din

e com

bine

d w

ith

pegi

nter

fer

on a

lfa-2

a an

d rib

aviri

n fo

r 48

wee

ks in

ch

roni

c he

patit

is C

vi

rus-

1 in

fect

ion.

2008

( III

)

(PEG

-

(RB

V)

[

(AM

A)

]

2a+R

BV

+A

MA

352

2a+R

BV

+

352

45

AM

A :18

5

167

46.3

76.7

kg:

183

169

45.4

74.0

kg

18A

LTC

(1)

: HIV

HB

V ()

(QT

)

: 200

37

~200

72

SVR

()

SVR

AM

A17

1/3

52(4

8.6%

)18

6/3

52(5

2.8%

)A

MA

32%

23%

(P=0

.01)

52/7

05(7

.4%

)A

MA

3128

81

()

PEG

-

AM

A

158

8Y

u M

L,

et a

l.

Rap

id

viro

logi

cal

resp

onse

an

d tre

atm

ent

dura

tion

for c

hron

ic

hepa

titis

C

geno

type

1

patie

nts:

a ra

ndom

ize

d tri

al.

2008

(

)

(24

482 )

24 1

0048

100

(1

3 )

24:

57(5

7%)

49.7

65.5

kg48

:58

(58%

)49

.1

67.5

kg

18~6

5A

LTC

(1) (

):

HC

V1

HB

VH

IV

: 200

54

~200

75

SVR

()

SVR

2459

%48

79%

(P=0

.002

)24

36.6

%48

12.2

%(P

<0.0

001)

243%

4810

%(P

=0.0

45)

241

481

RV

R 2448

200

No

CQ

159

8

Zeuz

em

S, e

t al

.

Alb

inte

rfer

on a

lfa-2

b do

sed

ever

y tw

o or

four

w

eeks

in

inte

rfero

n-na

ïve

patie

nts

with

ge

noty

pe 1

ch

roni

c he

patit

is

C.

2008

( IIb

)

(PEG

-

(RB

V)

[Alb

inte

rfero

2b+R

BV PE

G-

2a+R

BV

]

2a+R

BV

114 2

1)+

RB

V 1

18

21

)+R

BV

110

41

)+R

BV

116

8 8

2

:57

.9% 41

.9

73.4

kg

21

):

55.9

% 42.5

74.6

kg

21

):

58.2

% 41.3

76.4

kg

41

):

67.2

% 42.7

77.3

kg

ALT

C(1

):

HB

VH

IV

: 200

55

~200

75

SVR

()

SVR

57.9

%2

1)

58.5

%2

1)

55.5

%4

1)

50.9

%(P

=0.6

4)28

.9%

alb-

21

)20

.9%

21

)30

.7%

41

)28

. 4%

(P=0

.34)

6.1%

21

)9.

3%2

1)

18.2

%4

1)

12.1

%(P

=0.0

4)1

()

IIb

HC

V1

2b+R

BV

2a+R

BV

2b+R

BV

160

8

And

riu

lli

A, e

t al

.

Early

di

scon

tinu

atio

n of

rib

aviri

n in

HC

V-2

an

d H

CV

-3

patie

nts

resp

ondi

ng

to P

eg-

inte

rfero

n al

pha-

2a

and

ribav

irin.

2009

(

)

(PEG

-IFN

)

(RB

V)

[4

(RV

R)

RB

V PEG

-

2a+R

BV

]

RV

R RB

V 59

2a+R

BV

61

7

RV

RR

BV

:59

%

52.7

3

73.0

6kg

2a+R

BV

:49

%52

.59

70.6

1kg

18~7

0A

LTC

(23

):

HIV

: 200

57

~200

610

SVR

()

SVR

RB

V32

/59

(54%

)2a

+RB

V50

/61

(82%

)(S

VR

28%

95%

CI:

26.5

-29.

5, P

<0.0

01)

RB

V27

/59

(46%

)10

/61

(17%

)(

29%

95%

CI:

27.5

-30.

6,

P<0.

001)

RB

VIF

NR

BV

63%

PEG

-IFN

66%

RV

R

RB

V

)

700,

000I

U/m

LR

VR

RB

VPE

G-

201

No

CQ

161

8B

ress

ler B

, et

al.

Phar

mac

oki

netic

s an

d re

spon

se

of o

bese

pa

tient

s w

ith

chro

nic

hepa

titis

C

treat

ed

with

di

ffere

nt

dose

s of

PEG

-IFN

al

pha-

2a

(40K

D)

(PEG

ASY

S).

2009

(

)

(PEG

-

g/)

20

20

(

)

:12 8

47.3

99.0

kg

(BM

I 34.

0)

:14 6

44.3

98.0

kg

(BM

I 31.

4)

18(B

MI 3

0)

ALT

C(

):

: 200

28

~200

43

SVR

()

SVR

14/2

0(7

0%)

15/1

9(7

9%)

1SV

R8

/14

(57%

)10

/14

(71%

)4

BM

I 30

1

162

8

Hé

zode

C

, et

al;

PRO

VE2

St

udy Te

am

.

Tela

prev

ir an

d pe

gint

erfe

ron

with

or

with

out

ribav

irin

for c

hron

ic

HC

V

infe

ctio

n.

2009

( IIb

)

(PEG

-

(RB

V)

(

)

334

: 4

T12P

R24

(PE

G-IF

N

12

2a+R

BV

1224

) 81

T12P

R12

(PE

G-IF

N

12) 8

2T1

2P12

(

2a12

)78 PR

48(

-2a+

RB

V48

12

) 82

:28

HC

V 1

T12P

R24

:54

46B

MI

24T1

2PR

12:

49

44B

MI

23T1

2P12

:43

45B

MI

24PR

48:

4645

BM

I24

18~6

5A

LTC

(1)

:2

2006

82

~200

71

17

SVR

()

S VR

: HC

V-

RN

A:

00

SVR

46.

3%(3

8/8

2)

SVR

T12P

R12

T12P

1248

%PR

48(

)46

%T1

2PR

12SV

R60

%T1

2P12

SVR

36%

(P=0

.003

)T1

2PR

24SV

R69

%PR

48(P

=0.0

04)

Gra

de3

3~7%

T12P

R12

T12P

R24

7%12

3.0g

/dL

3.1-

3.9g

/dL 12

%7%

HC

V1

T12P

R24

PR48

SVR RB

V

SVR

202

No

CQ

163

8Id

e T,

et

al.

A rand

omiz

ed

stud

y of

ex

tend

ed

treat

men

t w

ith

pegi

nter

fer

on a

lpha

-2b

plu

s rib

aviri

n ba

sed

on

time

to

HC

V R

NA

ne

gativ

e-st

atus

in

patie

nts

with

ge

noty

pe

1b c

hron

ic

hepa

titis

C.

2009

[

44(

68)

]

113

(

56 57)

1b

:26 30

55.3

BM

I 23.

1:

30 27

54.6

BM

I 23.

4

20~7

5A

LTC

(1b

):

HB

s

80,0

00/

32,

500/

mL

12g/

dL: 2

005

1~2

006

6:

24

SVR

()

SVR

20/5

6(3

6%)

30/5

7(5

3%)

(P=0

.07)

16~2

4SV

R1

/11

(9%

)7

/9(7

8%)

(P=0

.005

)7

/56

(12.

5%)

6/5

7(1

0.5%

)(P

=0.7

8)

SVR

30%

60% 44

164

8

Jens

en D

M,

et a

l.

Re-

treat

men

t of

pat

ient

s w

ith

chro

nic

hepa

titis

C

who

do

not

resp

ond

to

pegi

nter

fer

on-

alph

a2b:

a

rand

omiz

ed

trial

.

2009

(

)

(PEG

-

(RB

V)

A×1

2×

6072

B×1

2×

3648

C×7

272

D×4

848

942

(A31

7B

156

C15

6D

313

) :

106

A:

64%

48. 1

81.5

kgB

:60

%48

.8

81.1

kgC

:69

%49

.4

81.2

kgD

:68

%48

.5

80.9

kg

18 2b+R

BV

)C

()

: AB

HIV

HC

V

6

: 200

39

~200

54

: 200

72

SVR

()

SVR

A52

/317

(16%

)B

11/1

56(7

%)

C22

/156

(14%

)D

27/3

13(9

%)

AD

()

1.8

(95%

CI:

1.32

-3.0

2, P

<0.0

01)

SVR

12A

+B21

%C

+D13

%12

SVR

49%

(77

/157

)12

4%(3

2/7

19)

A37

(12%

)B

6(4

%)

C18

( 12%

)D

20(6

%)

1(

)72

(A+C

)48

(B+D

)(P

=0.0

02)

2b+R

BV

)C

()

(PEG

-

)

SVR

12

203

No

CQ

165

8

Kaw

aoka

T,

et

al.

Dos

e co

mpa

riso

n st

udy

of

pegy

late

d in

terfe

ron-

alph

a-2b

pl

us

ribav

irin

in n

aïve

Ja

pane

se

patie

nts

with

he

patit

is C

vi

rus

geno

type

2:

a

rand

omiz

ed

clin

ical

tri

al.

2009

(

)

(PEG

-

(RB

V)

2b

)

53(P

EG-

26PE

G-

27)

6

(

)

24

(57

55) 57

kg

20A

LTC

(2)

:IF

N

: 200

62

~200

710

SVR

()

SVR

10/2

6(3

8.5%

)20

/27

(74.

1%)

(P=0

.013

)2

/26

(7.7

%)

2/2

7(7

.4%

)1

11

3

2C

166

8La

ngle

t P,

et a

l.

Clin

ical

tri

al: a

ra

ndom

ize

d tri

al o

f pe

gyla

ted-

inte

rfero

n-al

pha-

2a

plus

rib

aviri

n w

ith o

r w

ithou

t am

anta

din

e in

tre

atm

ent-

naïv

e or

re

laps

ing

chro

nic

hepa

titis

C

patie

nts.

2009

(

)

(PEG

-

(RB

V)

[

(AM

A)

AM

A ]

AM

A 316

AM

A 314

( 37 )

AM

A :18

9

127

43.7

4

73.0

2kg

AM

A :17

3

141

45.4

8

73.1

2kg

18A

LTC

()

:6

HC

V HA

V

SVR

()

SVR

AM

A19

3/3

16(6

1.1%

)A

MA

192

/314

(61.

1%)

(P=1

.000

)A

MA

79/3

16(2

5%)

AM

A88

/314

(28.

03%

)(P

=0.4

17)

AM

A

204

No

CQ

167

8

McH

utch

iso

n JG

, et

al;

IDE

AL

Stud

y Tea

m.

Pegi

nter

fer

on a

lfa-2

b or

alfa

-2a

with

rib

aviri

n fo

r tre

atm

ent

of

hepa

titis

C

infe

ctio

n.

2009

(

)

(PEG

-

(RB

V)

2bPE

G-

2a)

3,07

0:

3

RB

V80

0~1,

400m

g/) 1

,019

RB

V80

0~1,

400m

g/) 1

,016

(PEG

-

g/ RB

V1,

000~

1,20

0mg/

)1,

035

118

40

18.6

%

83.4

kg(

3)

2a 2b1 R

BV

18H

CV

1H

CV

-RN

AH

CV

1,50

0/3

80,0

00/

3

12g/

dL(

)13

g/dL

()

: HIV

HB

V(

>8.5

%)

(>1

25kg

)

: 200

43

~200

66

:24

SVR

()

RN

A

(SV

R:

24 HC

V-

RN

A )( H

CV

-RN

A

)

SVR

339

.8%

38.0

% (2

P=0.

20,

1.8%

, 95%

CI:

-2.3

- 6.

0) P

=0.5

7,

-1.1

%, 9

5%C

I: -5

.3 -

3.0)

-2b

23. 5

%(9

5%C

I: 19

.9-2

7.2)

20.0

%(9

5%C

I: 16

.4-2

3.9)

31.5

%(9

5%C

I: 27

.9-3

5.2)

:

8.6~

11.7

%2.

1~5.

9%2.

1~3.

8%1.

8~2.

6%12

2(

)

HC

V1

3SV

R

168

8

Rob

erts

SK

, et

al;

Cha

rio

t St

udy G

rou

p.

Impa

ct o

f hi

gh-d

ose

pegi

nter

fer

on a

lfa-2

A

on

viro

logi

cal

resp

onse

ra

tes i

n pa

tient

s w

ith

hepa

titis

C

geno

type

1:

a

rand

omiz

ed co

ntro

lled

trial

.

2009

(

)

(PEG

-

(RB

V)

( 12

)

(12 )

433

438

(12

):

298

135

43.6

77.3

kg:

285

153

43.3

78.7

kg

18~7

5A

LTC

(1)

:1

HB

VH

IVH

CV

6

: 200

48

2006

(: 2

004

9~2

007

2)

SVR

()

SVR

(12

)23

0/4

33(5

3%)

219

/438

(50%

)(P

=0.2

9)(1

2)

105

/431

(24%

)11

2/4

35(2

6%)

(12

)46

/431

(11%

)45

/435

(10%

)1

(12

)11

9/4

33(2

7%)

45/ 4

38(1

8%)

C(1

)

12

12 SVR

205

No

CQ

169

8

Ros

sig

nol

JF, e

t al

.

Impr

oved

vi

rolo

gic

resp

onse

in

chr

onic

he

patit

is C

ge

noty

pe 4

tre

ated

w

ith

nita

zoxa

nide

, pe

gint

erfe

ron

, and

rib

aviri

n.

2009

(

)

(PEG

-

(RB

V)

2a+R

BV

48

(PEG

-IF

N+R

BV

)

(NTZ

) 12PE

G-

36(P

EG-

IFN

+NTZ

)N

TZ 1

2

2a+R

BV

+NTZ

36(P

EG-

IFN

+RB

V+N

TZ)

3

PEG

-IF

N+R

BV

40

PEG

-IF

N+N

TZ 2

8PE

G-

IFN

+RB

V+N

TZ28

2

PEG

-IF

N+R

BV

:36 4

40B

MI(

)28

PEG

-IF

N+N

TZ:

25 337

BM

I()2

7PE

G-

IFN

+RB

V+N

TZ:

27 137

BM

I( )25

18A

LTC

(4)

:IF

N

HB

V : 200

68

~200

82

SVR

()

1) S

VR

PEG

-IFN

+RB

V20

/40

(50%

)PE

G-

IFN

+NTZ

17/2

8(6

1%)

PEG

-IFN

+RB

V+N

TZ22

/28

(79%

)PE

G-IF

N+R

BV

PEG

-IFN

+NTZ

PEG

-IF

N+R

BV

+NTZ

(P=0

.023

)2)

PE

G-IF

N+R

BV

1PE

G-IF

N+N

TZ1

8(P

EG-IF

N+R

BV

5PE

G-IF

N+N

TZ3

)11

(PEG

-IFN

+RB

V5

PEG

-IFN

+NTZ

4PE

G-

IFN

+RB

V+N

TZ2

)

C(4

)

12N

TZ36

2a+R

BV

+NTZ

170

8

Rus

tgi

V

K,

et a

l; M

Eri

mep

odi

b TR

iple

cO

mbi

nat

ion

Stud

y Gro

up.

Mer

imep

odi

b,

pegy

late

d in

terfe

ron,

an

d rib

aviri

n in

ge

noty

pe 1

ch

roni

c he

patit

is C

pe

gyla

ted

inte

rfero

n an

d rib

aviri

n no

nres

pon

ders

.

2009

( IIb

)

(PEG

-

(RB

V)

2a+R

BV

(MM

PD)5

0m

g10

0mg

3 ]

117

MM

PD50

mg

119

MM

PD10

0m

g 1

18

62

:

69.2

%50

.0

89.7

kgM

MPD

50m

g:

60. 5

%48

.9

88.2

kgM

MPD

100m

g:

64.4

%49

.3

85.5

kg

18~7

0)

C(1

)(

1212

2-lo

g 24H

CV

-R

NA

):

RB

V

: 200

47

~200

610

(MET

RO

Stu

dy)

SVR

()

SVR

MM

PD50

mg

6/1

07(6

%)

MM

PD10

0mg

5/1

12(4

%)

5/1

04(5

%)

( P=0

.843

1)M

MPD

50m

g4

MM

PD10

0mg

65

+RB

VC

(1)

+RB

V+

MM

PD

MM

PD

206

No

CQ

171

8To

yoda

H,

et a

l.

Eigh

t-wee

k re

gim

en o

f an

tivira

l co

mbi

natio

n th

erap

y w

ith

pegi

nter

fer

on a

nd

ribav

irin

for p

atie

nts

with

ch

roni

c he

patit

is C

w

ith

hepa

titis

C

viru

s ge

noty

pe 2

an

d a

rapi

d vi

rolo

gica

l re

spon

se.

2009

(PEG

-

(RB

V)

[4

(RV

R)

8 24

]

RV

R8

15

RV

R24

17

(R

VR

24 2

8)

24 37

56.7

/=4

0/2

1

59.1

kg

C(2

)20

061~

6

SVR

()

RV

R32

/60

(53.

3%)

SVR

RV

R8

5/1

5(3

3.3%

)R

VR

2414

/17

(82.

4%)

(P=0

.014

0)R

VR

24SV

R15

/28

(53.

6%)

2

C(2

)PE

G-

RV

R 8

172

8

Asc

ion

e A

, et

al.

Pegi

nter

fer

on a

lfa-2

a pl

us

ribav

irin

is

mor

e ef

fect

ive

than

pe

gint

erfe

ron

alfa

-2b

plus

rib

aviri

n fo

r tre

atin

g ch

roni

c he

patit

is C

vi

rus

infe

ctio

n.

2010

(

)

(PEG

-

(RB

V)

2a+R

BV PE

G-

2b+R

BV

)

2a+R

BV

160

2b+R

BV

160

(

)

2a:

81 7951

.3

70.4

kg

2b:

94 6648

.9

69.9

kg

18A

LTC

(1~4

)

:

HB

VH

IVH

CV

2004

3~2

006

12

SVR

()

SVR

110

/ 160

(68.

8%)

PEG

-87

/160

(54.

4%)

(P=0

.008

)H

CV

-RN

A(5

00,0

00IU

/mL

)26

/320

(8.6

%)

14

3/9

3(3

.2%

)13

/93

(14%

)2

31

/67

(1.5

%)

9/6

7(1

3.4%

)

()

2a+R

BV

2b+R

BV

()

207

No

CQ

173

8

Bra

dy D

E,

et a

l.

Indu

ctio

n pe

gyla

ted

inte

rfero

n al

fa-2

b in

co

mbi

natio

n w

ith

ribav

irin

in

patie

nts

with

ge

noty

pes

1 an

d 4

chro

nic

hepa

titis

C:

a pros

pect

ive

, rand

omiz

ed,

m

ultic

ente

r, o

pen-

labe

l st

udy.

2010

(

)

(PEG

-

( 12 2b g/kg

g/kg

12

)

610

( 299

311

)46

:

49.7

%45

84.5

kg:

50.3

%45

84.8

7kg

ALT

C(1

4)

(Chi

ld-

Pugh

A)

:

HC

V1

4C

hild

-Pug

h A

(HB

V )H

IV

12

6

2002

3~2

005

3

SVR

()

SVR

96/2

99(3

2%)

92/3

11(2

9%)

(P=0

.434

)

()

2

SVR

12%

12PE

G-IF

N

C(1

4)

174

8

Kha

tta

b M

, et

al.

Piog

litaz

one

im

prov

es

viro

logi

cal

resp

onse

to

pe

gint

erfe

ron

alp

ha-

2b/ri

bavi

rin co

mbi

nati

on th

erap

y in

he

patit

is C

ge

noty

pe 4

pa

tient

s w

ith

insu

lin

resi

stan

ce.

2010

(

)

(PEG

-

(RB

V)

[

(

)

]

2b+R

BV

+

48

2b+R

BV

49

:14

(29.

2%) 40

BM

I 28

.63

:15

(30.

6%) 37

BM

I 28

.4

18C

(4)

: A

HA

HB

VH

IV

6 : 200

72

~200

94

SVR

()

SVR

29/4

8(6

0.4%

)19

/49

(38.

7%)

(P=0

.04)

34

+

SVR

208

No

CQ

175

8

Mec

ena

te

F, e

t al

; C

lub

Epat

olog

i O

spe

dalie

ri (CLE

O)

Gro

up.

Shor

t ve

rsus

st

anda

rd

treat

men

t w

ith

pegy

late

d in

terfe

ron

alfa

-2A

pl

us

ribav

irin

in p

atie

nts

with

he

patit

is C

vi

rus

geno

type

2

or 3

: the

cl

eo tr

ial.

2010

[4

(RV

R)

12

24

]

12 7

2

24 7

1

RV

R 2

4

67

RV

R:

116

(81%

)42

BM

I 24

RV

R:

54(8

0%)

45B

MI 2

5

ALT

C(2

3)

:6 H

I VH

BV

HC

V: 2

006

7~2

008

1

SVR

()

SVR

1260

/72

(83%

)24

53/7

1(7

5%)

RV

RSV

R33

/67

(49%

)12

0/7

2(0

%)

245

/71

(7%

)R

VR

7/6

7(1

0%)

C(2

3)

4(R

VR

)

12 24

SVR

176

8

Mé

ndez

-N

ava

rro J,

et

al.

A rand

omiz

ed co

ntro

lled

trial

of

doub

le

vers

us

tripl

e th

erap

y w

ith

aman

tadi

ne

for

geno

type

1

chro

nic

hepa

titis

C

in L

atin

o pa

tient

s.

2010

(PEG

-

(RB

V)

[

(AM

A)

]

2a+R

BV

63

2a+R

BV

+A

MA 61

2a+R

BV

:26 37

46.2

70.4

1kg

2a+R

BV

+AM

A:

29 3244

74.4

3kg

ALT

(1)

()

: HC

VH

IVH

BV : 2

003

3~2

005

6

SVR

()

SVR

25/6

3(3

9.7%

)26

/61

(42.

6%)

(P=0

.561

)

5/6

3(7

.9%

)6

/61

(9.8

%)

AM

A

AM

A

209

No

CQ

177

8

Rum

i MG

, et

al.

Ran

dom

ized

stud

y of

pe

gint

erfe

ron

-al

pha2

a pl

us

ribav

irin

vs

pegi

nter

fer

on-

alph

a2b

plus

rib

aviri

n in

chr

onic

he

patit

is

C.

2010

(

)

(PEG

-

(RB

V)

2b+R

BV

2a 2

12

2b 2

19

(

)

2a:

128

(60.

4%) 51

.6

72.2

kg

2b:

120

(54.

8%) 52

.8

68.9

kg

18~7

0A

LTC

(1~4

)

:A

LT(

:12

g /dL

13g/

dL)

2,50

0/3

1,50

0/3

75,0

00/

3

1.5

HIV

IFN

RB

V: 2

003

9~2

007

6

SVR

()

SVR

140

/212

(66%

)-2

b11

9/2

19(5

4%)

(P=0

.02)

1SV

R44

/91

(48%

)28

/87

(32%

)(P

=0.0

4)2

SVR

PEG

-66

/69

(96%

)61

/74

(82%

)(P

=0.0

1)3

SVR

22/3

4(6

5%)

2b22

/32

(69%

)(P

=0.9

)4

SVR

44%

31%

(P=0

.5)

1%1%

18(8

%)

23(1

1%)

(P=0

.6)

PEG

-

178

8

C

.

2011

(PEG

-IF

N)+

(RB

V)

20,0

72

2a: 1

2,13

9

2b: 7

,933

PubM

edEM

BA

SEC

ochr

ane

Libr

ary

PEG

-IFN

+RB

V

SVR

()

SVR

PEG

-

5.19

%(9

5%C

I: 4.

87-5

.52)

330.

17%

(95%

CI:

0.12

-0.2

4)0.

043%

(95%

CI:

0.01

8-0.

084)

210

CQ

9

No

CQ

179

9

Liaw

Y

F,

et a

l; C

irrh

osis

A

sia

n Lam

ivu

dine

M

ult

icen

tre

St

udy G

rou

p.

Lam

ivud

ine

for

patie

nts

with

ch

roni

c he

patit

is B

an

d ad

vanc

ed

liver

di

seas

e.

2004

(

)

B LMV

100m

g/

651

(LM

V43

6 215

):

41

LMV

:37

0(8

5%) 43

Chi

ld-P

ugh

5(78

%)

6(17

%)

7(5

%)

4(40

%)

5(29

%)

6(31

%)

:18

2(8

5%) 44

Chi

ld-P

ugh

5(73

%)

6(19

%)

7(8

%)

4(35

%)

5(26

%)

6(39

%)

: 6H

Bs

HB

eH

Bs

HB

V-D

NA

4:

(A

FP)

ALT

(10

)H

CV

HD

VH

I V(

)2

8g/d

L1,

500/

3

50,0

00/

36 LM

V

: “ ”

“”

Chi

ld-P

ugh

2 (HC

C)

72: L

MV

7.8%

(34

/436

)17

.7%

(38

/215

)(H

R: 0

.45,

P=0

.001

)C

hild

-Pug

h: L

MV

3.4%

(15

)8.

8%(1

9)

(HR

: 0.4

5, P

=0.0

2)H

CC

:LM

V3.

9%(1

7)

7.4%

(16

)(H

R: 0

.49,

P=0

.047

)1

HC

CH

CC

HR

: 0.4

7, P

=0.0

52

LMV

49%

YM

DD

Chi

ld-P

ugh

(7%

, <1%

)LM

V2

[(

)11

]14

(HC

C8

6) :

LMV

12%

(54

)18

%(3

8)

12LM

V12

4

BLM

V

HR

0.45

(95%

CI:

0.28

-0.7

3)

180

9Y

uen

MF,

et

al.

Long

-term

la

miv

udin

e th

erap

y re

duce

s th

e ris

k of

lo

ng-te

rm

com

plic

ati

ons o

f ch

roni

c he

patit

is B

in

fect

ion

even

in

patie

nts

with

out

adva

nced

di

seas

e.

2007

HBe

(LM

V)

(

>3.5

g/m

L

<1.5

×U

LN)

LMV 14

2

124

LMV

:10

636

33.9

(20.

2-54

.4)

:90

34 33.4

(20.

8-59

)

HB

eLM

V20

g/

: 199

46

~199

78

313

: 1994

61

~199

78

31

60

LMV

(P=0

.005

)Y

MD

D(

876

.3%

)Y

MD

DLM

VY

MD

DLM

V HB

V-D

NA

HB

e YM

DD

(P=0

.024

)H

BV

-DN

A(P

=0.0

01)

LMV

211

No

CQ

181

9

Papa

theo

dorid

is

GV

, et

al.

Out

com

e of

he

patit

is B

e

antig

en-

nega

tive

chro

nic

hepa

titis

B

on lo

ng-

term

nu

cleo

s(t)i

de a

nalo

g th

erap

y st

artin

g w

ith

lam

ivud

ine

.

2005

(LM

V)

(IFN

)

LMV 2

01

209

195

(

4 )

LMV

:16

752

31.8

%:

174

47 27.3

%:

160

49 34.9

%

HB

eB

HB

sH

BV

-D

NA

(Chi

ld-P

ugh

A)

:H

CV

HD

VH

IVIF

N 6

LMV H

BV

: 199

71

~200

112

LMV

(P=0

.11)

(P=0

.68)

(P=0

.036

)(P

=0.0

4)LM

V

(P=0

.10)

(P=0

.65)

(P=0

.02)

(P=0

.03)

ALT

HB

eB

LMV

182

9A

ras

e Y

, et

al.

Com

paris

on

of

Inte

rfero

n an

d La

miv

udin

e Trea

tmen

t in

Ja

pane

se

Patie

nts

With

H

BeA

g Po

sitiv

e C

hron

ic

Hep

atiti

s B

.

2007

(LM

V)

(100

mg/

) (IFN

)

327

IFN 1

79LM

V 148

IFN

(35

): 10

118

28[

]73

/28

/15

LMV

(35

): 97

2028

[]

47/

22/

4IF

N(3

5):

4614

43[

]17

/29

/15

LMV

(35

): 29

1242

[]

12/

15/

7

: 6A

LT(

2)

1

HB

eH

CV

: HC

V H

BV

()

1990

~200

4

HB

e

HB

eIF

N:

(35

) 2 3

1.1%

6 7

0.0%

(35

) 2 1

9.0%

6 4

7.1%

(P=0

.002

)LM

V: (

35) 2

36.

8%6

62.

8%(3

5)

2 2

7.4%

6 5

0.4% (P

=0.4

77)

IFN

LMV

HB

eO

R: 1

.14(

95%

CI:

0.84

-1.5

4)( P

=0.4

10)

: (IF

N)

(LM

V)

4

(P<0

.001

)

LMV

IFN

212

No

CQ

183

9

Sha

mliy

an

TA,

et a

l.

Ant

ivira

l th

erap

y fo

r ad

ults

w

ith

chro

nic

hepa

titis

B

: a

syst

emat

ic

revi

ew fo

r a

Nat

iona

l In

stitu

tes

of H

ealth

C

onse

nsus

D

evel

opm

ent

Con

fere

nce.

2009

(IFN

)

(PEG

-

2a

9360

(RC

T)

HB

e

20~1

,367

1990

~20

08

B RC

T

50

24

B:

78%

64%

30%

MED

LIN

EPu

bMed

Coc

hran

e Li

brar

y 1989

BR

CT

HB

eH

Bs

HB

V-D

NA

ALT

:

HB

eH

Bs

HB

V-

DN

AA

LT

1)

16R

CT(

4,43

1)

B

2)

60R

CT

HB

s

ALT

HB

eH

Be

ALT

HB

eA

L T

HB

eA

LT3)

B

4

215

46

Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, Arase Y, Fukuda M, Chayama K, Murashima N, Kumada H.

Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients.

J Hepatol

( ): 28(6): 930-938

1998

(IFN) 61.7%(1,366 )HBgroup43.1%(263/610) HCgroup71.1%(1,067/1,500) HBHCgroup60.8%(31/51)NBNCgroup9.4%(5/53)

2,215 ( 1,544 671 )HBgroup(610)=HBs HCgroup(1,500)=HCV HBHCgroup(52)=

NBNCgroup(53)=

HBgroup: 60.7%(475/610) 34 (13-66 )HCgroup: 66.3%(995/1,500) 49 (16-75 )HBHCgroup: 82.7%(43/52) 43.5 (25-63 )NBNCgroup: 58.5%(31/53) 47 (25-75 )

: 47

1980~1995 8 ( )

: :

1) 2)

1

1) HBgroup10.2%(62/610) HCgroup6.1%(92/1,500)HBHCgroup7.7%(4/52) NBNCgroup5.7%(3/53)2) B C 5 8.0% 8.4%3) HBgroup3.3%(20/610) HCgroup4.3%(64/1,500)HBHCgroup3.8%(2/52) NBNCgroup5.7%(3/53)4) 5 3.4% B 2.1% C 4.8%

5) HBgroup HCgroup 5 98.7% 99.0%; 10 97.4% 97.4%; 1590.0% 90.5%

1) 160 (7.2%) 0.1~16.32) IFN 60%

216

47

Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ; Taiwan Community-Based Cancer Screening Project Group.

Hepatitis B e antigen and the risk of hepatocellular carcinoma.

N Engl J Med

( ): 347(3): 168-174

2002

HBs HBe RIA

HBs HBe : 370HBs HBe : 1,991HBs HBe : 9,532

7

: 30~65

: 7 47,079 11,893 (25%): (HCC)

HCC

National Cancer Registry

1) HCC (100,000 ) HBs HBe 39.1(95%CI: 26.2-56.1) HBsHBe 324.3(95%CI: 240.7-427.5) HBs HBe

1169.4(95%CI: 799.9-1650.9)2) Cox HCV

HBs HCC 9.6(95%CI: 6.0-15.2) HBe60.2(95%CI: 35.5-102.1)

BHBe B 1%

217

48

Ikeda K, Arase Y, Kobayashi M, Someya T, Hosaka T, Saitoh S, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Kumada H.

Hepatitis B virus-related hepatocellular carcinogenesis and its prevention.

Intervirology

( ): 48(1): 29-38

2005

1) 2)

1) (HCC) 48 HCC 482) (IFN) (4 )

1) / =39 /9 49.5 /492)

1) 1976~1989 HB 217 IFN160 146 HCC 48 HCC

98 HCC 1:1 48 HCCHCC 7.2 HCC 11.7

2) 1983~1990 HB 189 5713.6

Type A: IFN HBV Type B: IFN HBV Type C: IFN HBV Type D: IFN HBV

HBV

AFP CT

1) HCC HCC 3 HBV-DNA HCCAFP

2) HCC TypeA 15.8% Type B 12.5% Type C 33.3% Type D 40.4%IFN HBV-DNA Type HCC

1) 2

2) HBV-DNA HCC IFN HBV-DNAHCC

218

49

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group.

Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.

JAMA

( ): 295(1): 65-73

2006

HBV-DNA (HCC)

3,653

7

30~65HBs HCV

: HCC HCV

HCC

( CT ) (AFP): 11.4 (41,779 )

1) 11.4 HCC164 3462) HBV-DNA HCC HCC HBV-DNA300copies/mL 108/100,000 1,000,000copies/mL 1,152/100,000

1.3% 14.9%3) HBe ALT

HBV-DNA HBe ALT HCC

219

50

Ishiguro S, Inoue M, Tanaka Y, Mizokami M, Iwasaki M, Tsugane S; JPHC Study Group.

Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based cohort study in Japan.

Eur J Cancer Prev

( ): 18(1): 26-32

2009

19,812 [ 18,576 1,236 (HBV479 HCV737 HBV+HCV20 )]

6,920 12,892

: ALT

(HCC)

: 1993~2005 11.8 (234,016 )

1) 109 ( 71 38 ) HCC2) HCC 10 ALT<30IU/L 1.1% ALT30-69IU/L 11.1% ALT 70IU/L24.9%

1) 0.1%2) ALT HCC

220

51

Pagliaro L, Peri V, Linea C, Cammà C, Giunta M, Magrin S.

Natural history of chronic hepatitis C.

Ital J Gastroenterol Hepatol

( ): 31(1): 28-44

1999

1) 9872) 4,1853) 1,470

Research question

1) C2) C3) C4) C

MEDLINE (1989.1~1997.12): chronic hepatitis, non-A, non-B hepatitis, hepatitis C, natural history, course,

prognosis, case-control, cohort and cross-sectional studies, alcohol, iron, transaminases, liver cirrhosis, HCC, genotype, viraemia, and blood donors

1) 3 8(HCC) 6~18 5

67% (49~91%)2) 8 12~44 HCC 15~45

3) 13 1,470 4~12 8~12 727.9% 2

3.5% 11.7%4) C

1)

2) ‘non-A, non-B hepatitis’

221

52

Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, Morabito A, Colombo M.

The Natural History of Compensated Cirrhosis Due to Hepatitis C Virus: a 17-Year Cohort Study of 214 Patients.

Hepatology

( ): 43(6): 1303-1310

2006

23 (11%) 9 ( ) (IFN)

214

C [Child-Pugh A, 55 (35 ) (HCC)RNA ]

: : RNA CP B

17114 ( : 1-199 )

214 152 5

( : )

AFP

66 ( )( ) HCC36 (17%) 13 (6%) 50

(23%) 36 (17%) 2 (1%)HCC3.9% 2.9% 2.0% 0.7%

0.1% 4% 154(72%) HCC AFP(>20ng/mL)

(<146 × 109/L) (<4.3g/dL) 73 (35%)2.0%

HCV

11% IFN (31%)

HCC ( 2.8% 1.4%) (3.9%)

222

53

Zhang BH, Yang BH, Tang ZY.

Randomized controlled trial of screening for hepatocellular carcinoma.

J Cancer Res Clin Oncol

( ): 130(7): 417-422

2004

( )

( ) 2 AFP

( )9,757 9,443

: 42 41: 62.6% 63.3%

: 35~59 B (HBs) 6 (AST ALT )

: (HCC)

: 1993 1 ~1995 12: 1997 12 1998 12

GP( ) Shanghai Cancer Registry

1) HCC 279.3/100,000 267.0/100,0001.37(95%CI: 0.99-1.89)

2) HCC 100,000 83.2/131.5 0.63(95%CI: 0.41-0.98)

1) : HCC 86 713 (

) 12 GP Shanghai Cancer Registry2) B 2 AFP

HCC 37%

223

54

Chen TH, Chen CJ, Yen MF, Lu SN, Sun CA, Huang GT, Yang PM, Lee HS, Duffy SW.

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan.

Int J Cancer

( ): 98(2): 257-261

2002

1 =HBs HCV AFP( 20ng/mL) AST( 40IU/L) ALT( 25IU/L)2 = 1 6 1

6

4,385

7

1) 4,3852) 458

1) : 1 6 12) : 1 6 1

1) 2)

1) 4,385 68 458 9

2) 24%(95%CI: 52-62%)3) 1.57 (95%CI: 0.94-4.68)

2.66 (95%CI: 1.68-3.37)4) ( ) HB HC ALT AFP

224

55

Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L, Zanetti M, Sherman M.

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

Gut

( ): 48(2): 251-259

2001

6 AFP

313 104

: 1989 3 ~1991 11: (HCC)

: 1989 3 ~1991 11

HCC

( )

56

1) HCC 61 (19.5%) 4.1%2) AFP Child-Pugh B C ( )3) (P=0.02) 3

45% 31.7%

1) (ICER) US$141,918/

2) 3) US$17,934

225

56

, , , , , , , .

.

( ): 88: 63-70

1990

AFP20ng/mL 36 (HCC)

878

1) 555 3232) 294 5293) HBs : 9.3% 7.7%

70 2.0mg/dL 3.0g/dL40~70 50~70 GOT

GPT 50

HCC

1) HCC 33 12 ( 5.1%) 34 1159.2

2) 2 81.9% 31.7% (P=0.0001)

1)

2) 1 87.8%(5 13.1%)2

226

57

, , , , , , , ,, .

.

( ): 46(1): 35-45

2008

113,992 39 ( ) 633

: 81% 61.1 : 66% 66.8: 53% 62.9 : 30% 69.7: 20% 58.0 : 60% 71.1

: 75% 61.3 : 60% 67.9: 80% 53.9 : 70% 64.9

: 70% 66.6 : 57% 65.2

1981~1995 16,515 1981~199533,089 1996~2004 64,338

(5 )

1) 5 10 15 36.2% 9.1% 4.6%18.2% 7.3% 4.4% (P<0.01) 38.8%

9.2% 4.6%2) 5 40.5% 40.4%

17.3%

1)

2) 3) 3 35.0~35.6% 5 33.3~33.7%

227

58

Palmer DR, Perry KR, Mortimer PP, Parry JV.

Variation in the sensitivity of HBsAg screening kits.

Transfus Med

( ): 6(4): 311-317

1996

15 HBs

1) 150 HBs low-level HBs 62) 223) 64) British HBsAg Working Standard (0.5IU/mL)5) NIBSC/UKBTS HBsAg Monitor Sample (0.125IU/mL)

( )

HBs ( )

HBs

1) 150 HBs 10 assays 1505 assays 149low-level HBs 6 4 assays(Auszyme Monoclonal, Monolisa Ag HBs 2nd generation, Murex HBsAg, Ortho HBsAg Test System 3)5 1 assay(Micro Trak II HBsAg) 12)

assay(Monolisa Ag HBs 2nd generation) 79 5 assays 70 7 assays60-69 2 assays 50-59 assay 31specimens HBs

3) 61 assay(Auszyme Monoclonal) 18 15 HBs

3 assays HBs 104) British HBsAg Working Standard 5 2 assays consistently unreactive

5) NIBSC/UKBTS HBsAg Monitor Sample 3 assays(Bioelisa, Enzygnost, Murex)consistently reactive 5 assays sometimes reactive 6 assays consistently unreactive

1) EIA HBs 15 HBs

2) 3)

228

59

Motte A, Colson P, Tamalet C.

Evaluation of the clinical performance of the Beckman Coulter Access AbHBsII immunoassay for the detection of hepatitis B surface antibodies.

J Clin Virol

( ): 37(3): 213-217

2006

HBsBeckman Coulter Access AbHBsII immunoassay Abbott Axsym test Vidas

1,207 ( 232 HBs HBV 150 HBs825 )

( ) 1

HBs: Access Axsym Access AxsymVidas: Access Axsym Access AxsymVidas

1) Access Axsym Vidas2) ( )

1) Access Axsym 95.8%97.8% 98.1% 96.0% 99.0%

>100mIU/mL 10-100mIU/mL <10mIU/mL Access Axsym>100mIU/mL 88.9% 10-100mIU/mL 76.8% <10mIU/mL 96.2%

2) 51 Access 8 (2 6HBV ) 15 (7 2 4 1

)

1) HBs2)

229

60

Shih LN, Sheu JC, Wang JT, Huang GT, Yang PM, Lee HS, Sung JL, Wang TH, Chen DS.

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction.

J Med Virol

( ): 32(4): 257-260

1990

HBV-DNA (PCR )

107

National Taiwan University Hospital

45 6244.9 ( : 14-75 )

6 HBs

: 1988 1 ~1990 6

HBV-DNA

PCR

107 8 (7.5%) HBV-DNAHBs HBc HBeHBs HBc : 7.4%(5/68)HBs : 0% (0/6)HBc HBe : 25% (1/4)HBc : 0% (0/9)

: 10% (2/20)

1) HBs HBV-DNA2) ( ) HCV HBV

230

61

Gomes SA, Yoshida CF, Niel C.

Detection of hepatitis B virus DNA in hepatitis B surface antigen-negative serum by polymerase chain reaction: evaluation of different primer pairs and conditions.

Acta Virol

( ): 40(3): 133-138

1996

ELISA (PCR )

20

HBs

HBs HBs HBc

1) PCR HBV-DNA 0~50%2) HBs 87~100%

1) HBs HBV2) HBs HBV

HBV HBV-DNA PCR

231

62

Togashi H, Hashimoto C, Yokozawa J, Suzuki A, Sugahara K, Saito T, Yamaguchi I, Badawi H, Kainuma N, Aoyama M, Ohya H, Akatsuka T, Tanaka Y, Mizokami M, Kawata S.

What can be revealed by extending the sensitivity of HBsAg detection to below the present limit?

J Hepatol

( ): 49(1): 17-24

2008

1) 2102) 368

1) 49.52) 49

1) 2) EIA HBs B

HBs

PCR

1) HBs 2.86% (6/210)2) B C 7.69%(5/65) B C 9.68%(6/62) C8.96%(12/134) C 10.28%(11/107)3) HBV-DNA PCR 9 B

1) HBs B(P<0.005)2) HBV

232

63

Colin C, Lanoir D, Touzet S, Meyaud-Kraemer L, Bailly F, Trepo C; HEPATITIS Group.

Sensitivity and specificity of third-generation hepatitis C virus antibody detection assays: an analysis of the literature.

J Viral Hepat

( ): 8(2): 87-95

2001

HCV

132 10HCV

RIBA PCR

1) 2) MEDLINE Excerpta Medica3) : hepatitis c, serodiagnosis, sensitivity, specificity

1) ELISA 98.9%(95%CI: 94-100) 100%

2) RIBA3 78.8%(95%CI: 65-89)

1) HCV2) PCR3) 100%

233

64

Sherman M, Peltekian KM, Lee C.

Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population.

Hepatology

( ): 22(2): 432-438

1995

6 AFP AFP

1,069 (AFP : 531 AFP+ : 538 )

( )

1989 2 ~1994 3 HBV 39 (±12 )65% 71%

1) 182) GP( )3) Liver Cancer Screening

1) (HCC)2)

: AFPCT

1) 26 (6-60 )2) 4% AFP 9%

3) 3 HCC 281/100,000HBV11 HCC ( 470/100,000)

657/100,0004) HCC 5 ( 214/100,000)5) ) HCC 64.3% 91.4%

71.4% 93.8%

1) HCC

2) (RCT) feasibility study

3) RCT 2 HCCAFP

234

65

Tong MJ, Blatt LM, Kao VW.

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.

J Gastroenterol Hepatol

( ): 16(5): 553-559

2001

HCV HBV AFP (US)AFP US

602HC=429 /HB=160 /HB+HC=13

356 (59%) 246 (35%)51 (±14 )

(HCC)

AFP(6 ) US(1 ) ALTUS AFP CT

: 1991~1999 : 34.5±24.5(12-103)

1) AFP 6 US 1 31 HCC2) HCC US 100% 98% (PPV) 78%AFP ROC 65% 90%

AFP 13ng/mL3) AFP HCC 74% 10%AFP PPV 12% ROC 65% 90%4) US PPV 78% 100% 98%HCC 24 (77%) 16.7±19.4

1) HCC AFP

US 100%

HCC2) US 1

CT USAFP CT

AFP USPPV

3) AFP PPV

235

66

, , , , .

.

( ): 33(2): 169-173

1995

7,022 (1981 ~1987 )

40~69

:

88.9% 99.4%

1)

2) 3)

236

67

, , , , , .

1 .

( ): 71(2): 128-130

2009

1

71

Finn chambers Scanpor tape

ICDRG

237

68

Erdmann SM, Sachs B, Merk HF.

Allergic contact dermatitis due to methyldibromo glutaronitrile in Euxyl K 400 in an ultrasonic gel.

Contact Dermatitis.

( ): 44(1): 39-40

2001

1

62

RWTH

ICDRG

(Euxyl K 400) methyldibromo glutaronitrile()

238

69



Cardiovasc Intervent Radiol

( ): 28(5):584-588

2005

(INRAD 18G Express core needle biopsy system )

153

Veterans Affairs Medical Center

52 ( : 30-83 )

2000 1 ~2003 2 Veterans Affairs Medical Center138 (90.2%) C

INR 1.5 >70,000/ 3

1) : 4

2) :3) : 1cm

4SpO2

3 60

41.2%

28 (18.2%)3 2 (1.3%)

239

70

Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A.


Gut

( ): 36(3): 437-441

1995

1,500

health district 189

806 69460-69

health district 189 British Society of Gastroenterology 1 11991 1 10

:

79%(1500/189)1) 563 (38%)

507 (34%)2) Tru-cut type (Abbott) 66% Menghini type62% ( )3) 83% excellent( ) satisfactory( ) 5%

26 (1.7%): 11 1 9INR (20

) Tru-cut /: 2 (44 :

71 : )3 ( ) 1,500

0.13~0.33%

1) 1991 1 40% 62%

2)

240

71

Piccinino F, Sagnelli E, Pasquale G, Giusti G.


J Hepatol

( ): 2(2): 165-173

1986

68,276

Liver Unit 36

Liver Unit 10 40036 Liver Unit 1973~1983

50% 50,000/ 3

Menghini type 60,611 Tru-cut type 7,372 Vim-Silverman type 293

4,527 9,367 18,73522,729 1,755 11,163

147 (2.2%) ()

[ ]Menghini type 120 (2.0%) Tru-cut type 26 (3.5%) Vim-Silverman type 1(3.4%)[ ] 2 (0.44%) 22 (2.34%)

52 (2.78%) 52 (2.29%) 5 (2.85%) 14 (1.25%)6 (0.009%) 100,000 9

[ ]Menghini type 3 Tru-cut type 3[ ] 3 3

1) 1970~80

2)

241

72

Myers RP, Fong A, Shaheen AA.


Liver Int

( ): 28(5): 705-712

2008

1994~2002 9 4,275 (3,627 )

( )

43% 509 9 (

)

( 99%):

32 (0.75%) [ 22 (69%) 15 (47%) 8(25%) 3 (9%) 6 (19%)]

11 10 3 2 21(91% vs. 94%)

6 (0.14%) 5 1

242

73

Vivas S, Palacio MA, Rodríguez M, Lomo J, Cadenas F, Giganto F, Rodrigo L.

Ambulatory liver biopsy: complications and evolution in 264 cases.

Rev Esp Enferm Dig

( ): 90(3): 175-182

1998

( )4

264 ( : 114 )

( )

65% 42: 66% 7%

5% ( )

:

264 5 ( 1 3 1 )18%

83% 24(1.9% vs. 1.7%)

1) 0.9-3.7%(1978~1995 )2) 18% 2%

243

74

Sugano S, Sumino Y, Hatori T, Mizugami H, Kawafune T, Abei T.


Dig Dis Sci

( ): 36(9): 1229-1233

1991

( )

4575

2

: 24-72: 22-74

2:

6 24

1) 9 (20%) 13 (17%) ( 18.3%)2)

244

75



Am J Gastroenterol

( ): 91(7): 1318-1321

1996

753

Casa Sollievo della Sofferenza: 40,000/ 3 40%

1) 745 /7532) : 1 (0.13%) 3 3.5% 0.9%3) 1

1) 0.13%(0.21-5.9%)2) 0-0.33%

245

76

Froehlich F, Lamy O, Fried M, Gonvers JJ.


Dig Dis Sci

( ): 38(8): 1480-1484

1993

3,501

80

1) 280 252 ( 90.0%)2) 165 3,5013) 0.31%( 5 3 1 needle rupture1 )4) 3 (0.08%)

1)2)

246

77

van der Poorten D, Kwok A, Lam T, Ridley L, Jones DB, Ngu MC, Lee AU.


Intern Med J

( ): 36(11): 692-699

2006

2462% 46%

1,398 (1986~1995 : 444 1996~2005 : 954 )

1

1,398 : 213 799 204 67%/ 33% 18~88( 43 )

59.6%(1996~2005 )66%

C (37.8%) B (26.4%) (22.2%)

1996~2005 Concord Repatriation General Hospital1986~1995

: 188

: 2Minor( ) :Major( ) : 20g/L

1996~1999 188

1990166 (13.6%) 12 (1%) 10 1

13 (0.25%)

100×109/L 1674 7 (9.8%)

10 18.5% 10 10.8%

10 1.35% 10 0.78%(P=0.508)

10 (63.9%)

1) 24 1,3981% 0.25%

2) 1% (0.32~0.59%)

247

78Lindor KD, Bru C, Jorgensen RA, Rakela J, Bordas JM, Gross JB, Rodes J, McGill DB, Reading CC, James EM, Charboneau JW, Ludwig J, Batts KP, Zinsmeister AR.


Hepatology

( ): 23(5): 1079-1083

1996

( )

(US) Tru-cutUS

836 (489 347 )(1) Tru-cut US 204 (2) Tru-cut US 216 (3) US 209 (4) US 207

( ) ( ): 45% 50(16-90) : 67%

40(13-72) 54% 47(13-90)4.7% 43.5% 7.2%

(79.4% vs. 18.2%)

: ( )489 Hospital Clinico y Provincial de Barcelona ( )347

:50,000×106/L

10g/dL 3: 1992 1 ~1994 1

: 15 40 Hg80 Hg 25% / 2 / 3

30 Hg 80 Hg

( )

24 2

1) 1.3%(11 /836 ) US 2 US 9 (P=0.04)2) US 9 US 18 (P=0.07)3) US 14) US 37% US 50%(P=0.003)5) US (

Tru-cut )US Tru-cut

(P<0.005)6) 2

7) 121

1) US US

2) 4

248

79


Percutaneous liver biopsy: a safe outpatient procedure?

Digestion

( ): 63(1): 55-60

2001

1,581

1

1993~1999 1,318 263

: ( ):

( )

1) 0 12) 0 13) 15.9% 15.2%4) 3 15)

1)2) 1

249

80

Chuah SY, Moody GA, Wicks AC, Mayberry JF.

A nationwide survey of liver biopsy--is there a need to increase resources, manpower and training?

Hepatogastroenterology

( ): 41(1): 4-8

1994

( )

364

1 INR 2

81.3%206 ( 80

11 13 30 53 19 )95%

20 /5.2/10,000 5.6/1,000

2

250

81

Cammà C, Giunta M, Andreone P, Craxì A.

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.

J Hepatol

( ): 34(4): 593-602

2001

[ (RCT) ]

(IFN)

1) HC 3RCT 11 RCT 3,109 (HCC) 3562) HB 7 RCT 1,505 HCC 122

C B

1) MEDLINE(1985~1999 ): hepatocellular carcinoma, interferon, cirrhosis, clinical trial, cohort study

2) (1995~1999 ): RCT RCT HCC

HCC

1) IFN C SVR( )

2) HCV HBV HCC12.8%(95%CI: 8.3-17.2) 6.4%(95%CI: 2.8-10.0)3) HCV SVR HCC non responder (RD: 11.8%, 95%CI:5.9-14.2)4) HC HCC 6.8-37.7%

1) C BHBV HCC

2) IFN C B

3) IFN RCT RCT 3

251

82Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL.Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma.Aliment Pharmacol Ther

( ): 28(9): 1067-10772008

:

1) (IFN)[ (PEG-IFN) ] 2) ()

1) IFN : 2,742 2) : 2,2891) IFN : 1997~2007 12 ( 110 1) 2,742 ( 71.0% 36.74.7~8.9 )2) : 2004~2007 5 ( 2

2 1) 2,289 ( 78.6% 42.82.7~8.2 )

5 1

1) : B IFN(PFG-IFN )( )

(HCC)2) :HCC3) :

B HCC

1) IFN :Pooling 0.66(95%CI: 0.48-0.89)

34%

2) :Pooling 0.22(95%CI: 0.10-0.50)

78%

HBe HBe3) : 5 ( : 1~5 5 )

( 3 )IFN ( : 0.64 95%CI: 0.44-0.93)

1) IFN B HCC

2) IFN

3)

4)

5)

252

83

Miyake Y, Kobashi H, Yamamoto K.

Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection.

J Gastroenterol

( ): 44(5): 470-475

2009

(IFN)

8 1,3031) (RCT)3 RCT52) 3 3 1 1

PubMed 1998 1 ~2007 12

=hepatitisB, interferon, HCC

: 1) IFN 2) HCV HIV 3) (HCC) 4) HCC

HCC

1) HCC (RD: 5.0%; 95%CI: 9.4 - 0.5)2)

(RD: 8.5%; 95%CI: 13.6 - 3.6)

1) PubMed 82) 8 IFN3) IFN4) HBV-DNA

253

84

Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF.

Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.

Hepatology

( ): 29(3): 971-975

1999

( )

(IFN)(67 ) 31 IFN 36 IFN

101 ( 67 34 )

( )

IFN (31 )32±8 32±29IFN+ (36 )31±6 41±36

(34 )32±6 41±58

17~55Hbe

: Liver Research Unit:

IFN 6.9±3.2IFN+ 7.8±2.8

7.4±2.4

(HCC)

3~6 ( AFP )

1) 24 1 (4.2%)36 7 (19.4%)

8 0 21 5 (23.8%)(P>0.05)

2) 67 HCC1 (1.5%) 34 HCC4 (12%) (P=0.043)3) 1 4 10 98% 85%

1) ( ) 22) 3) 2

254

85

Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.

Lancet

( ): 351(9115): 1535-1539

1998

(IFN) [ 4.2%(160 ) 28%(107 ) IFN

281 356

(B and/or C) Child-Pugh A: C: IFN

( ):

: 21:: 1 3

( )

1) (HCC) 10.3%(29/281) 18.5%(66/356)1.99(95%CI: 1.09-3.64)

2) HC HCC 9.1%(21/232) 18.5%(48/259)3.14(95%CI: 1.46-6.80)3) HB HCC 16%(8/49) 19%(18/97)0.98(95%CI: 0.33-2.92)

C B IFN

2)

3) 4) 2

255

86

Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, Shiomi S, Seki S, Kobayashi K, Otani S.

Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.

Lancet

( ): 346(8982): 1051-1055

1995

(RCT) ( )

90 ( 45 45 )

: 28 /17 54.7±5.8: 23 /22 57.3±6.9

1) C2) HBs

(HCC)

CT: 1988 1 ~1992 6

: 2~7

1) HCC 19 : 2 17 (P=0.002)2) 0.067(95%CI: 0.009-0.530)3) 5 2

2 HCC

1) IFN RCT: IFN HCC2) 80%

256

87

Azzaroli F, Accogli E, Nigro G, Trere D, Giovanelli S, Miracolo A, Lodato F, Montagnani M, Tamé M, Colecchia A, Mwangemi C, Festi D, Roda E, Derenzini M, Mazzella G.

Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study on patients with HCV related cirrhosis.

World J Gastroenterol

( ): 10(21): 3099-3102

2004

(RCT) ( )

HCV (IFN)+ (RBV)

60 30 (TG: treatment group)30 (CG: control group]

1 IFN 41 (OTCG: old treatment control group)

: 60 ( 35 25 ) 55.7±1.7OTCG : 27 14 55.0±1.1

:HCV

(HCC)

AFP AST ALT 3

: 51) (TG) 1 IFN+RBV 6

2) OTCG IFN 6 19 8(SR)OTCG IFN AgNOR-PI(Ag stained nucleolar organizer region -proliferative index)3) AgNOR-PI>2.5% HCC 9/35(26%) AgNOR-PI<2.5%

2/66(3%)TG 21 (VR) 13 SR4) HCC TG CG 9 OTCG non-responder( )

2TG CG (P<0.003) OTCG CG (P<0.004)

5) (CG) HCC 5%6) TG IFN RBV1) RCT 2 1 RCT

(AgNOR-PI) RCT

2) IFN+RBV HCC(RCT )

3) IFN RBV4) RCT AgNOR-PI

257

88

Benvegnù L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A.

Retrospective analysis of the effect of interferon therapy on the clinical outcome of patients with viral cirrhosis.

Cancer

( ): 83(5): 901-909

1998

(IFN)

189 ( 88 101 )

: 122 (64.5%) 67 (35.5%) 58.2±8.2( : 36-75 )

HBs 28 (14.8%) HCV 152 (80.4%) HBs HCV9 (4.8%)

: 59 29 56.7±8.0: 63 38 59.5±8.3

: 1 1986~1993Child-Pugh A B C

:

1) Child-Pugh2) (HCC)3)

CT(AST ALT ALP AFP) 6

HCC: 1986~1993

71.5 ( : 23-125 ): IFN 71.9 71.4

1) Child-Pugh 7 (7.9%) 22(21.8%) (P<0.01)2) HCC 5 (5.6%) 27 (26.7%)

3 (3.4%) 20 (19.8%) (P<0.001, P<0.005)3) IFN4) HBs

2 HCV

5) SVR( )HCC SVR

1) IFN3

2) (95%CI)( P )

3) Fisher

258

89

Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M.

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

Ann Intern Med

( ): 131(3):174-181

1999

(IFN)2,400 84% 14% 2%

: 480 MU (first quartile 324 MU; third quartile 702 MU): 160 (first quartile 94 ; third quartile 168 )

2,890 C ( 2,400 490 )

8

: 1,531 869 49.5±11.3: 270 220 53.6±11.2

: 8 1986 C

: 3,223 161 1 172

(HCC)

4.3

1) HCC : 1.10%(89 /2,400 ) 3.17%(59 /490 ) (P<0.01)HCC

2) F0 F1 0.5% F4 7.9%F2 (P=0.0128) F3 (P=0.0011)

3) IFN HCC (0.516, 95%CI: 0.358-0.742) (

0.197, 95%CI: 0.099-0.392) ALT ( 0.197, 95%CI: 0.104-0.375) ALT 2 ( 0.358, 95%CI: 0.206-0.622)

1) IFN HCC2) 3) F0 F1 IFN HCC

4) HCV HCC

259

90

Valla DC, Chevallier M, Marcellin P, Payen JL, Trépo C, Fonck M, Bourlière M, Boucher E, Miguet JP, Parlier D, Lemonnier C, Opolon P.

Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.

Hepatology

( ): 29(6): 1870-1875

1999

(RCT) ( )

(IFN) 3,000,000 3 24 ]

99 47 52 )

8

: 1.55/ 2.36: 56 57

: 18~75 12 HCV ( )

( B )HIV >50×103/ 3 >1,200/ 3 IFN

RCT: [ ] ( 44 48 AST ALT)

[ ]( 48~72 )

AFP: ( ) (HCC)

RCT: 4 481

: 3~6: 1993~1995

: 1993~1997 (RCT 4 72 1997 9 )

1) 47 62

2) AFP

3) HCC 5 9 6 510 7 3

IFN 87% ( )3 5

1) HCV HCV-RNA2) RCT IFN

3) RCT 72 IFN1997 9

260

91

Mazzella G, Accogli E, Sottili S, Festi D, Orsini M, Salzetta A, Novelli V, Cipolla A, Fabbri C, Pezzoli A, Roda E.

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.

J Hepatol

( ): 24(2): 141-147

1996

(IFN)

347 ( 227 120 )

1

213 51HBV /HCV 34 /193 28/92 (HCV A B

HCV )HBV HCV

: 1 HBVHCV (Child-Pugh A)

(HCC)

1) AFP 6~82) HCC CT AFP

: 1984~1994: [ ] HBV 49 /HCV 32 [ ] HBV

48 /HCV 34

1) HCC 20 (HBV6 /HCV14 )2) HCC (RR=9.6, P<0.007) IFN (RR=4.4, P<0.02)3) IFN HBV HCV4) HCC IFN 4.4 (95%CI: 1.5-13.5)

HBV4.9 (95%CI: 0.2-95.2)/HCV4.0 (95%CI: 1.2-13.5)5) IFN

1) HCV IFN ALT2) HCC

HCV3) HBV HCC

4) HBV

261

92

Ikeda K, Arase Y, Saitoh S, Kobayashi M, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Kumada H.

Anticarcinogenic impact of interferon on patients with chronic hepatitis C: a large-scale long-term study in a single center.

Intervirology

( ): 49(1-2): 82-90

2006

(IFN) ( 30 )

2,166 ( 1,654 512 )

: 67.1% 50: 60.7% 53

: HBs HCV: (HCC) HBV

HCC

1) : 12) ( CT): 1~23) HCC

: 1970~2004 ( 2004 5 1 ): 10.7 ( : 0.1-33.6)

1) HCC 5.8%(96 /1,654 ) 20.1%(103/512 )2) 5 HCC 2.6% 4.6% 10 5.8%

12.7% 15 13.9% 23.9% (P<0.0001)3) HCC F1 F2~F3 8.68(95%CI: 5.08-14.81) 502.64(95%CI: 1.58-4.42) 2.38(95%CI: 1.56-3.70)4) 3.1%(52 /1,654 ) 12.5%(64 /512 )

1) C IFN HCC

2) IFN (2 : 240 3 : 56 )3)

4) 223 (10.3%)

262

93

Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, Arakawa Y, Hashimoto E, Hirota K, Yoshida H, Ohashi Y, Omata M; Tokyo-Chiba Hepatitis Research Group.

Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival.

Ann Intern Med

( ): 142(2): 105-114

2005

(IFN) 3 / 32~88 )]

C 345 ( 271 74 )

25

137 208: 102 169 57

: 35 39 61

: HCV-RNA (Child-Pugh A) >50,000/ 3 >3,000/ 3

: HBV

(HCC)

1~2 3~6HCC CT MRI

: 1996~2002: 6.8 ( : 0.04-10.4 )

1) SVR( ) 23.6%(64 /271 )2) HCC : 119 [ 84 (31.0%) 35 (47.3%)]3) (

0.65, 95%CI: 0.43-0.97, P=0.03) SVR ( 0.31, 95%CI: 0.16-0.61, P<0.001)4) 69 [ 45 (17%) 24 (32%)]5) IFN ( 0.54, 95%CI: 0.33-0.89, P=0.02)

SVR ( 0.05, 95%CI: 0.006-0.34, P=0.003)

1) IFN SVR

2) IFN

263

94

Yu ML, Lin SM, Chuang WL, Dai CY, Wang JH, Lu SN, Sheen IS, Chang WY, Lee CM, Liaw YF.

A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan.

Antivir Ther

( ): 11(8): 985-994

2006

(IFN) IFN+ (RBV)

1,065 565

: 39.5% 46.9±11.49: 38.3% 43.6±14.0

: C: B HIV

(HCC)

( ): 5.18 (1.0-15.3 ) 5.15 (1-16 )

1) HCC 51 (12.2%) 54 (35.2%) (P=0.0013)2) HCC 0.95% 1.92%3) 16 (1.5%) 12 (2.1%)

SVR( )0.4% Non-SVR3.2%(P=0.022)1.8%(P<0.0001)4) 96.2% 93.1% (P=0.3928)

1) IFN IFN+RBV SVR2)

3) 4) IFN IFN+RBV IFN+RBV

264

95

Ikeda K, Arase Y, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Kumada H.

Necessities of interferon therapy in elderly patients with chronic hepatitis C.

Am J Med

( ): 122(5): 479-486

2009

[ (IFN) (HCC)]

IFN IFN+ (RBV) : 454 (23.7%)

1,917 [ 454 (IFN 413 RBV 41 ) 1,463 ]

: 214 240 62 (60-80 ): 660 803 65 (60-88 )

: 60 HCV (HCV HCV-RNA HBV ): 6

HCC

1~31

1) HCC 10.8%(49 /454 ) 19.5%(285 /1,463 ) IFN0.67(P=0.045)

2) / 5 97.5% / 93.2% 10 89.9% / 70.8% 15 64.9% / 41.2% (P=0.0001)3) ALT HCV Cox

(HR) HCC<150,000/ 3 IFN

(HR: 0.56, P=0.035) 150,000/ 3

IFN 3910 (25.6%) 10 (25.6%) 6 (15.4%) 4

(10.3%) 9 (23.1%)

1)

2) 2.6% 11.3% (P<0.001)3) IFN 53.8%(186 /346 ) IFN+RBV

IFN

265

96

Gramenzi A, Andreone P, Fiorino S, Cammà C, Giunta M, Magalotti D, Cursaro C, Calabrese C, Arienti V, Rossi C, Di Febo G, Zoli M, Craxì A, Gasbarrini G, Bernardi M.

Impact of interferon therapy on the natural history of hepatitis C virus related cirrhosis.

Gut

( ): 48(6): 843-848

2001

/ 3 3 3 69MU

72 72

( ) 1

: 33 / 39: 57.9 58.1

Child-Pugh(A/B): 60 /12

: 1992 5 ~1994 5 IFN: 5 Child-Pugh

: ALT HCV HBs HIV( ) (HCC)

HCC ( )

(6 ) AFP (3 )( ): 55 (2-70 ) 58 (27-71 )

1) 7 (10%) 9 (12.5%) 2

2) 48 (13-60 ) 52 (37-60 )

3) HCC 6 19 2 5 HCC1.5% / 11% 11% / 27% 2 5 (P=0.0006,

P=0.013)4) IFN

1) IFN

2) AFP20ng/mL HCC 17% 66%

266

97

Soga K, Shibasaki K, Aoyagi Y.

Effect of interferon on incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Hepatogastroenterology

( ): 52(64): 1154-1158

2005

( )

recombinant(2b

103 30

1

: 50 53 52.2±14.0: 13 17 53.5±11.7

: C: B (HCC)

HCC

1992 1 ~1996 7 2001 8: 7.8±1.8

5 HCC 5 (4.9%) 7 (23.3%) (P<0.01)

1)

2) IFN

267

98Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, Tsubota A, Nakamura I, Murashima N, Kumada H, Kawanishi M.Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.Hepatology

( ): 29(4): 1124-11301999

(IFN) (HCC)

733 (61.5%) 6,000,000~9,000,000 IFN 8 2~316 RIA ELISA

1,643 ( 1,191 452 )

( A): 802 389 50 (15-86 )( B): 280 172 53 (21-78 )

: ( P<0.0001) ( P=0.040) ( P=0.016) ( P=0.00016) ALT(

P=0.0001) ( P=0.0050) ICG R15( P=0.0017) HCV(genotype 1a 1b P=0.0028) HCV ( P<0.0001)( F1 P=0.0015)

: 1974~1995 C: HBs HCC

HCC : CT: CT 1~2

1~2 CT 1~2( ): 5.1 (0.1-11.3 ) 8.2 (0.5-22.8 )

: 52 551) IFN 12CR(complete response)=HCV-RNA 461 (38.7%) IR(incomplete response)=HCV-RNA

ALT-normal(6 )145 (12.2%) NR=no response585 (49.1%)2) HCC : 25 (2.5%) 67 (14.8%) (P=0.02)HCC : 5 2.1% / 4.8% 10 7.6% / 12.4%(P=0.036) CR IR

3) CR+IR/NR/ HCC : 5 1.5% / 2.7% / 4.8% 10 1.5% / 14.9% / 12.4% (P=0.0011)4) HCC

5) Cox 4 IFN HCCIFN CR IR

[0.32(95%CI: 0.13-0.78)]6) : 6 / 35 5 : 99.6% / 98.1% 10 : 98.8% / 95.6% (P<0.001)

28 (2.4%) IFN22 (1.8%) 9 (0.8%) 5 (0.4%) 5

(0.4%) 5 (0.4%) ( )4 (0.3%) 13(1.1%) [ 63 (5.3%)]

1) IFN CR IR2) CR IR3) IFN4) HCC

268

99

Inoue A, Tsukuma H, Oshima A, Yabuuchi T, Nakao M, Matsunaga T, Kojima J, Tanaka S.

Effectiveness of interferon therapy for reducing the incidence of hepatocellular carcinoma among patients with type C chronic hepatitis.

J Epidemiol

( ): 10(4): 234-240

2000

(IFN)

923 ( 224 699

: 70.1% 64 5.8%: 56.1% 64 24.6%

1987 5 ~1995 3HCV HBs

(HCC)

3~6 AFP: 54.9 70.4: HCC 1997 12

1) HCC 2.2% 9.5% (P=0.0015)2) 4 (1.8%) 84 (12.0%)3) HCC 0 344) 5 HCC 2.2%(95%CI: 0-4.4) 9.5%(95%CI: 7.1-11.9) (P=0.0015)5) IFN HCC 69% (HR: 0.31, 95%CI: 0.12-0.80)6) HCC 0.82(95%CI: 0.18-3.71)

1) ALT2) 3) 4) 5) IFN

269

100

Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL; HALT-C Trial Investigators.

Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.

N Engl J Med

( ): 359(23): 2429-2441

2008

( )

3.5

1,050 ( 517 533 )

10

(517 ): 30.0% 51.1±7.3 no response 30.2%(533 ): 30.8% 50.1±7.0 no response 30.8%

HCV genotype(P=0.02): 1=95.2% 2=1.2% 3=2.1% 4 or 6=1.6%

: 1=91.6% 2=2.8% 3=4.1% 4 or 6=1.5%

: 24298 SVR( )

237: C IFN

3 12 1.5 3.5: 2000~2004

: 1,400

1) 1,400 34.1%(95%CI: 29.8-38.5)33.8%(95%CI: 29.4-38.1) 1.01(95%CI: 0.81-1.27)2) 38.6% 31.8%

(P=0.07)

IFN C

270

101

Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshioka K, Kawata S, Tanaka E, Hino K, Hayashi K, Tamura S, Itoh Y, Kiyosawa K, Kakumu S, Okita K, Hayashi N.

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.

J Viral Hepat

( ): 11(2):148-156

2004

(IFN)

2,698 256

)

: 1,738 960 53: 157 99 54

C

IFN 3~6 162 512

: 5.8 8.0

1) SMR(standardized mortality ratio: )0.9(95%CI: 0.7-1.1) 2.7(95%CI: 2.0-3.0)

2) SMR 5.5(95%CI: 4.3-6.9) 22.2(95%CI: 16.0-30.0)

1) IFN

2)

271

102

Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A, Silini EM, Almasio PL, Maisonneuve P.

Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study.

Am J Gastroenterol

( ): 104(5): 1147-1158

2009

) 2003 IFN+

352 ( 194 158 )

( )

1989~1992 359 (21-70 )51 (15.6%)

: HCV ( ): 71 Child-Pugh C (HCC)

HBV HIV

Child-Pugh B HCC

6( ): 14.4 (0.9-19.5 )

1) (SVR: )28 HCC 7 (25.0%) 4(14.3%) (Non-SVR)166 HCC 49 (29.5%) 46(27.7%) 158 HCC 53 (33.5%) 60 (38.0%)

2) (HR: 2.27, 95%CI: 1.41-3.66)3) MELD(model for end-stage liver disease) 11 2.15(95%CI: 1.50-3.09)

1) 20%2) (Non-SVR)3) MELD 10

272

103Fartoux L, Degos F, Trépo C, Goria O, Calès P, Tran A, Buffet C, Poynard T, Capron D, Raabe JJ, Roulot D, Naveau S, Grange JD, Poupon RE, Poupon R, Serfaty L.Effect of prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a randomized trial.Clin Gastroenterol Hepatol

( ): 5(4): 502-5072007

( )

C (IFN)PCR HCV-RNA

102 3,000,000 3 2 51 51 10

23 28 60.5IFN : 23 28 60.5 (SD: 9.7 : 35-75 )

: 23 28 60.5 (SD: 9.4 : 31-75 )

: 10 (1) 18~75 (2) (3) 2 (4)PCR HCV- RNA (5)

(6) (7)AFP (HCC) (8)HBs (9) (10)HIV

(11) (12) 1 : 56<80%

<35g/L <130,000/mL AFP>20ng/mL<50ng/mL:

AFP>50ng/mL HBV HIV >40g/3 2 ( AFP

) 6 24: 1999 1 ~2002 10

SDS index (Zung Self-Rating Depression Scale) ( <50 50~59 60~69 70)

3 3~6

1) 2 24.5% HCC12 HCC13 HCC

2) IFN 98%(12 ) 72.3%(24 )90%(12 ) 70.7%(24 ) (P=0.59)3) IFN 17.1 13.6

(P=0.2)4) IFN C

5) IFN HCV-RNA 26) : IFN 51 26 (9 ) (17 ) IFN

1) C IFN22) 2 HCC

IFN HCV HCV

3) 2 HCC

273

104

Arase Y, Ikeda K, Suzuki F, Suzuki Y, Kobayashi M, Akuta N, Hosaka T, Sezaki H, Yatsuji H,Kawamura Y, Kobayashi M, Kumada H.

Prolonged-interferon therapy reduces hepatocarcinogenesis in aged-patients with chronichepatitis C.

J Med Virol

( ): 79(8): 1095-1102

2007

(IFN) + (IFN+RBV)

120 240

: 1991~2006 C IFN 60

: 60 C IFN

1991 4 ~2006 3 IFN IFN+RBV 4,250720

IFN 1 60 HCV-RNA ALT6 1.5

12 HBsIFN >2,500/ 3 >70,000/ 3

<2.0 mg/mL CT (HCC)

120 3,000,000 2~3 2.47IFN

SDS index (Zung Self-Rating Depression Scale)( <50 50~59 60~69 70)

3 3~6

1) HCC IFN 4 IFN 382) 5 /10 HCC 5.9% / 13.7%17.1% / 32.8%3) HCC AFP>10ng/mL IFN4) IFN HCC 0.3

HCC 3.9

60 IFN HCC

274

105

Koskinas J, Merkouraki P, Manesis E, Hadziyannis S.

Assessment of depression in patients with chronic hepatitis: effect of interferon treatment.

Dig Dis

( ): 20(3-4): 284-288

2002

(IFN) ( )

132

Hippokration Hospital

C (HCV) 38 ( 26 12 43 )B (HBV) 36 ( 29 7 51 )

58 ( 24 34 57 )

(20 )

<10g/

SDS index (Zung Self-Rating Depression Scale) ( <50 50~59 60~69 70)

3 3~6

1) SDS index HCV 34.4 ( : 26.3-67.5) HBV40.0 ( : 27.5-61.3) 35.6 ( : 27.5-61.3) HCV

HBV (P=0.01)2) HBV HCV SDS index HBV HCV

(P=0.001)3) SDS index4) SDS index (P=0.008)5) SDS index6) : SDS index 70 HBV 2.8% HCV 21%5.5% 31.6%7)

1) IFN2)

275

106

Kanda Y, Shigeno K, Matsuo H, Yano M, Yamada N, Kumagami H.

Interferon-induced sudden hearing loss.

Audiology

( ): 34(2): 98-102

1995

1) ( 3 )2) (IFN) ( 73 )

2) IFN

1) 32) 73

1) 57 55 622) 32 ( 21 11 ) : 25~63

1) C IFN 32) B C 73 ( 1 )

2) IFN 20dB

2)

1) 3 C 2IFN 1

IFN2) 73 32 : 17 /35(48.6%) : 15 /38 (39.5%)] 17 (23.2%) 27(36.9%)

IFN IFN 7~14

: 43.8%

IFN

276

107

Del Monte P, Bernasconi D, De Conca V, Randazzo M, Meozzi M, Badaracco B, Mesiti S, Marugo M.

Endocrine evaluation in patients treated with interferon-alpha for chronic hepatitis C.

Horm Res

( ): 44(3): 105-109

1995

(IFN)IFN 3 6

31C

( )

18 (24~48 ) 13 (26~60 )C IFN

:

IFN 3 6

1) T4 IFN 3 6(P<0.05)

2) T33) TSH TRH 64)

45) 6) IGF-I IGF-I ALT

IFN

277

108

Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E.

Influence of psychiatric diagnoses on interferon- treatment for chronic hepatitis C in a veteran population.

Am J Gastroenterol

( ): 96(1): 157-164

2001

12 ( 6 )

33

32 1

C

( )

C IFN (68% > 29%)(P=0.024)

1)

2) ( :)

3) 4)

278

109

Martín-Santos R, Díez-Quevedo C, Castellví P, Navinés R, Miquel M, Masnou H, Soler A,Ardevol M, García F, Galeras JA, Planas R, Solà R.

De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C.


( ): 27(3): 257-265

2008

DSM-IV Axis I disorders (SCID-I) Patient Health Questionnaire(PHQ) Hospital Anxiety and Depression Scale (HADS)

(IFN)

17630 146

( )

119 5745 (SD: 1 )

C 24: 2004 1 ~2005 9 2 acute-care teaching

hosptial ) (800~1,200mg ) C (HCV 24 48 )

4 12 24 PHQ HADS: HBV HIV

AFP

6

( )

IFN (DSM-IV 1 ) IFN 4 12 24(PHQ HADS-D)

1) 53 /146 (36%)2) 27.8 (95%CI: 2.82-333 ) 3.1 (1.40-7.03 ) 3.2 (1.12-9.47 ) IFN+

3) 79% 90%(P=0.04)

4) : (36%)

1)

2) IFN

279

110

Glue P, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK, Salfi M, Jacobs S, Clement RP.

A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. The Hepatitis C Intervention Therapy Group.

Hepatology

( ): 32(3): 647-653

2000

(RBV)

72

35 3739.8 ( : 20-68 )65.6kg

ALT C

SVR( )

1) 02) 03) SVR 23% (11 /48 )

1) 2) PEG-IFN RBV

280

111

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK.

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

Lancet

( ): 358(9286): 958-965

2001

(RBV)

1,530[Higher-dose PEG-IFN+RBV(High PEG ) 511 Lower-dose PEG-IFN+RBV(Low PEG )514 IFN+RBV(IFN ) 505 ]

/ : High PEG 321 /190 Low PEG 346 /168 IFN 336 /169: High PEG 43 Low PEG 44 IFN 43: High PEG 82kg Low PEG 83kg IFN 82kg

ALT C

SVR( )

1) +RBV2) 03) 04) SVR: High PEG 54%(274 /511 ) Low PEG 47%(244 /514 ) IFN 47%(235/505 )

1)2) PEG

281

112

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J.

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

N Engl J Med

( ): 347(13): 975-982

2002

(RBV)

1,121 )453 )444(PEG+ )224 ]

81

/ : PEG+RBV 324 /129 IFN+RBV 325 /119 PEG+ 151 /73: PEG+RBV 42.8 IFN+RBV 42.3 PEG+ 42.4: PEG+RBV 79.8kg IFN+RBV 78.4kg PEG+ 79.1kg

ALT C: IFN ALT

6144 (13%)

: HIV 1.51

: 1999 2 ~2001 4 : 24

SVR( )

1 2 4 6 852 60 72

1) 2 ( 1 1 ) 0 SVR 56.3% (255 /453 )2) 2 3 HCV PEG+RBV IFN+RBV SVR

(76% vs. 61%, P=0.005) 1 HCV HCV-RNA(2,000,000copies/mL ) SVR PEG+RBV 41% IFN+RBV 33% PEG+13% SVR PEG+RBV 43% IFN+RBV

33% PEG+RBV 1 ( 3.25, 95%CI: 2.09-5.12) 40 ( 2.60, 95%CI: 1.72-3.95) 75kg ( 1.91, 95%CI: 1.27-2.89) SVR (VR)(HCV-RNA 2log

HCV-RNA ) PEG+RBV 86% 12VR 12

12 HCV-RNA HCV-RNA 2logSVR VR 61 SVR3) : PEG+RBV ( 3% /

7%) PEG+ (1% / 6%) IFN+RBV (1% / 10%)( ) PEG+RBV VR

(80% ) SVR(67% vs. 75%) VR SVR

(12%) ( ) 3 1~8PEG+ (2.2g/dL) PEG+RBV

(3.7g/dL) IFN+RBV (3.6g/dL) PEG+RBV 1 IFN+RBV 1(<500/ 3) IFN+RBV PEG-IFN

2 8 4 ( )PEG+ 1 IFN+RBV 1 PEG+RBV 4 PEG+

1 IFN+RBVPEG+RBV PEG+ IFN+RBV (22% vs. 20% vs. 30%)

282

113

Bosques-Padilla F, Trejo-Estrada R, Campollo-Rivas O, Cortez-Hernández C, Dehesa-Violante M, Maldonado-Garza H, Pérez-Gómez R, Cabrera-Valdespino A.

Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial.

Ann Hepatol

( ): 2(3): 135-139

2003

(RBV)

32 )14 )12-2a+ (PEG+ )6 ]

/ : PEG+RBV 6 /8 IFN+RBV 5 /7 PEG+ 2 /4: PEG+RBV 46 IFN+RBV 45 PEG+ 45: PEG+RBV 75kg IFN+RBV 68kg PEG+ 81kg

ALT C: 1999 2 ~2001 4

SVR( )

1) 02) 03) SVR: PEG+RBV 50%(7 /14 ) IFN+RBV 33.3%(4 /12 ) PEG+ 0%(0

/6 )

1)2) IFN+RBV 1

283

114

Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN, Mayet I, Khan MQ, Kessie G.

Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4.

Liver Int

( ): 24(6): 568-574

2004

(RBV)

96 ]

/ /26 /16

ALT C (4 ): 2001 6~10

SVR( )

1) 02) 03) SVR 43.8% (21 /48 )

1 ( )

284

115

Bruno S, Cammà C, Di Marco V, Rumi M, Vinci M, Camozzi M, Rebucci C, Di Bona D, Colombo M, Craxì A, Mondelli MU, Pinzello G.

Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial.

J Hepatol

( ): 41(3): 474-481

2004

(RBV)

311 [ ]

(62%) (62%)

ALT C (1 ): 2000 1~6

SVR( )

1) 02) 03) SVR (P=0.030) 41.1%(67 /163 ) 29.7%(44 /148 )

1) 24 77 (24.8%)2) PEG-IFN IFN (22% vs. 11%)3)

285

116

Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G,Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM;PEGASYS International Study Group.

Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomizedstudy of treatment duration and ribavirin dose.

Ann Intern Med

( ): 140(5): 346-355

2004

24 48 (RBV)(800mg/ ) (1,000 1,200mg/ )

1,311

: 99

838 42.3 77.3kgHCV-RNA2,000copies/mL ALT

ALT C

: A B HIV130g/L 120g/L

1.5

: 1999 11 ~2002 1: 12~24

SVR( )

1) 4 ( 2 ) 103 SVR 56%(720 /1,284 )2) HCV 1 483) HCV 2 3 244) 48 24 SVR (P=0.002)5) RBV SVR (P=0.01)6)

: :

286

117

Hasan F, Al-Khaldi J, Asker H, Al-Ajmi M, Owayed S, Varghese R, Siddique I, Al-Nakib B.

Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.

Antivir Ther

( ): 9(4): 499-503

2004

(RBV)

63 [ ]

(76%) (80%)

:

ALT C

SVR( )

1) 02) 03) SVR: 4.8%(1 /21 ) 7%(3 /42 )

1)2) 80%3) AMA AMA

287

118

Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, Lok AS, MorganTR, Bonkovsky HL, Lee WM, Dienstag JL, Ghany MG, Goodman ZD, Everhart JE; Hepatitis C AntiviralLong-Term Treatment Against Cirrhosis Trial Group.

Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

Gastroenterology

( ): 126(4): 1015-1023; discussion 947

2004

) (RBV)( 75kg 1,000mg/75kg 1,200mg/ )20 HCV-RNA 48 24 16RBV

(IFN) 180 135 90 RBV 600mg/20 HCV-RNA HALT-C ( )

3.5 3.5 IFN RBV

604 35 20 HCV-RNA

438 49.9 89.2kgHepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C)

IFN

: 10 HCV HCV-RNA 1Ishak 3-6 IFN

4 12 HCV-RNA

:3+ 2+

Child-Turcotte Pugh 6HIV

1.5<10g/dL

: HALT-C 2001 8~12 : 24

20 HCV-RNA (VR)(EVR) 12 2log HCV-RNA

(EOT) 48 HCV-RNA(SVR) HCV-RNA 72 ( 24 )

1) 0 0 SVR 18%(109 /604 )2) 20 5.6% 20 60% HCV-RNA

210 (35%) 2018 24 HCV-RNA

192 (32%) EOT IFN RBV VR 78 (41%) 5 72SVR 109 (18%) SVR

IFN 2 3 AST/ALT RBV20 80% 60% SVR21% 11% (P<0.05) HCV-RNA

20 IFN RBV SVR3) : 16 573 IFN 84 (15%)RBV 103 (18%) 122 (21%) RBV 7% IFN 0.3%

3%

CBC HCV-RNA

288

119

Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, Farci P, Gitlin N, O'Brien CB, Lamour F, Lardelli P; PEGASYS Study NR16071 Investigator Group.

Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels.

Gastroenterology

( ): 127(6): 1724-1732

2004

(RBV) 800mg/ 24 (212 : A )48 (210 : B ) (69 ) 3:3:1 (1 1 )

PEG-IFN 13590 RBV 600mg/ RBV (Hb) 10g/dL

4 Hb 2g/dLHb 8.5g/dL 12g/dL

RBV PEG-IFN

491

: 70

198 43.4 73.4kg18% 2 9.5% 3~4 1.4

ALT C: 18 HCV HCV-RNA C

ALT (3 4 1 42 26~18 ) ALT 30IU/L

ALT

36 Ishak:

(1,500/ 3 ) (90,000/ 3 )(Hb : 12g/dL 13g/dL ) HIV HBV HAV

1.5 () 1

6 2

: 2000 8 ~2003 4: 72

A B 24 SVR( )SVR

HCV-RNA A B 4 12 24 B 36 48 12 24 PCR4 12 24 36 48 60 72

HCV-RNA

1) 1 ( 0 ) 13 SVR 40.8%(172 /422 )2) SVR 24 48 30% 52% ( 1.7, 95%CI: 1.4-2.2, P<0.001)

HCV 1 SVR 48 40% 2413%( 3.1, 95%CI: 1.9-4.9, P<0.001) 2 3

SVR 4SVR 1 (24 13% 48 56%) 1

4 SVR (1 2416% 9% 48 47% 27% 4 24 17% 0% 48 67%33%) 2 3 24 483) : 77% 24 48

(24 7% 48 18%)24 2% 48 3% 1 7

6% ALT (30~59IU/L 60~149IU/L 150IU/L ) 2440% 14% 2% 48 38% 11% 1% 45% 6% 1%

1)

2) 69 ( )

289

120

Herrine SK, Brown RS Jr, Bernstein DE, Ondovik MS, Lentz E, Te H.

Peginterferon alpha-2a combination therapies in chronic hepatitis C patients who relapsed after or had a viral breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of efficacy and safety.

Dig Dis Sci

( ): 50(4): 719-726

2005

(RBV)

123 [(MMF)29 (AMA)31

]

/ /8 /92a+AMA 19 /12 /11

:

ALT C

SVR( )

1) 02) : 13%(4 ) 14%(5 ) 16%(5 ) 19%(6 )3) SVR: 37.5% 17% 10% 45%

1) 4 (7~19%)2) (48~69%) (47~61%) (35~74%) (19~52%) (32~41%)

3) 19 4

290

121

Jacobson IM, Gonzalez SA, Ahmed F, Lebovics E, Min AD, Bodenheimer HC Jr, Esposito SP, Brown RS Jr, Bräu N, Klion FM, Tobias H, Bini EJ, Brodsky N, Cerulli MA, Aytaman A, Gardner PW, Geders JM, Spivack JE, Rahmin MG, Berman DH, Ehrlich J, Russo MW, Chait M, Rovner D, Edlin BR.

A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C.

Am J Gastroenterol

( ): 100(11): 2453-2462

2005

(RBV)(A +RBV800mg/ (B+RBV1,000~1,200mg/

321

( ) 19

239 8249.5 ±7.4

ALT C: HBs 160 160

: 2000 2 ~2001 3: 24

SVR( )

1) 0 31 SVR 15.6%(50 /321 )2) A B3) HCV-RNA

(P=0.002)4) 1 (P=0.01)5) (P=0.01)6) 7) :

1) A B (8% vs. 11%, P=0.45)2) 24

291

122

Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz AA, Madwar MA.

Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response.

Gut

( ): 54(6): 858-866

2005

(RBV)

287 95 962b+RBV48 96 ]

/ : (A)24 49 /46 (B)36 51 /45 (C)48 50 /46: (A)24 41.6 (B)36 43.9 (C)48 41.2

ALT C: 2002 1 ~2004 5

SVR( )

1) 02) 83) SVR: 54.7% (157 /287 ) 24 29% 36 66% 48 69%

1) 3 48

2) ( )

3)

292

123

Lee SD, Yu ML, Cheng PN, Lai MY, Chao YC, Hwang SJ, Chang WY, Chang TT, Hsieh TY, Liu CJ, Chen DS.

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan.

J Viral Hepat

( ): 12(3): 283-291

2005

(RBV)

153 ]

/ /23 /25

ALT C: 2001 8 ~2002 12

SVR( )

1) 1 ( 0 )2) 53) SVR 67.1% (51 /76 )

:

293

124

Lodato F, Azzaroli F, Brillanti S, Colecchia A, Tamé MR, Montagnani M, Muratori R, Giovanelli S, Feletti V, Bacchi Reggiani ML, Roda E, Mazzella G.

Higher doses of peginterferon alpha-2b administered twice weekly improve sustained virological response in difficult-to-treat patients with chronic hepatitis C: results of a pilot randomized study.

J Viral Hepat

( ): 12(5): 536-542

2005

(RBV)

65 [(group A) 1 22 (group B) 2 43 ]

/ : (group A) 1 12 /10 (group B) 2 23 /20: (group A) 1 48.7 (group B) 2 49.6:

ALT C: 2001 11 ~2002 4

SVR( )

1) 02) 03) SVR: 52.3% (34 /65 ) group B 72% vs. group A 25% (P=0.024)

1) 2) group A 32%(7 /22 ) group B 19%(8 /43 ) ( )3)

294

125

Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, BaccaD, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A.

Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.

N Engl J Med

( ): 352(25): 2609-2617

2005

(RBV)

283 [standard-duration( ) )70 variable-duration() 24 )213 ]

( ): standard-duration 39 (56%) variable-duration 119 (56%): standard-duration 49.7 variable-duration 46.6: standard-duration 69.5kg variable-duration 69.4kg

ALT C (2 3 ): 2002 6 ~2004 1

SVR( )

1) 02) 03) SVR 76.7% (217 /283 )

1) 24 122) 12 4%(6 ) 24 9%(14 )3)

295

126

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S.Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.Gastroenterology

( ): 129(2): 522-527

2005

(RBV)) RBV 800~1,200 mg/ ( 65kg 800mg 65~85kg

1,000mg 85kg 1,200mg) 4 HCV-RNA 600IU/mL(rapid virological response: RVR) 8 16 (A )

24 (B ) RVR 24(C )

153 [A 71 B 71 C 11 ]

6 3/ : A 52 /19 B 41 /30 C 4 /7

: A 38 B 39 C 42: A 75.3kg B 74.6kg C 80.1kg

ALT C (2 3 ): 18 C ( 2 3 )

RBV HCV-RNA600IU/mL 18

ALT12g/dL 13g/dL

: HIV HBV

1

: 2002 2 ~2004 3 : 24SVR( )

1) 0 7 SVR 77.8% (119 /153 )2) 4 11 RVR (VR)88% SVR A 82% B 80%97.5%CI 11.5% RVR C SVR36% B

VR C 72% B 84%2 SVR92% 3 73%

3 800,000IU/mLSVR59% 800,000IU/mL 85% 2 A

B SVR 3 HCV-RNA 800,000IU/mLA B 800,000IU/mL SVR A 67% B 55%

(P>0.2)3) : 7 (

) B 1A 1 B 5 C 2

16 24 IFNRBV 14% 11%

(3%) (6%)

IFN

296

127

Zeuzem S, Pawlotsky JM, Lukasiewicz E, von Wagner M, Goulis I, Lurie Y, Gianfranco E, Vrolijk JM, Esteban JI, Hezode C, Lagging M, Negro F, Soulier A, Verheij-Hart E, Hansen B, Tal R, Ferrari C, Schalm SW, Neumann AU; DITTO-HCV Study Group.

International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C.

J Hepatol

( ): 43(2): 250-257

2005

268

179 89: 41.6 ±10.2: 74.3kg±13.4kg

ALT C: 2001 2 ~2003 11

SVR( )

1) 02) 193) SVR: 60% 60%

1) 2)

297

128

Abergel A, Hezode C, Leroy V, Barange K, Bronowicki JP, Tran A, Alric L, Castera L, Bernard PH, Henquell C, Lafeuille H, Ughetto S, Darcha C, Chevallier M, Martineau N, Dubost S, Randl K, Dhumeaux D, Bommelaer G, Bonny C; French multicenter study group.

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b.

J Viral Hepat

( ): 13(12): 811-820

2006

(RBV)

203+RBV(800mg/ )48 101 +RBV(800mg/

)48 102 ]

+RBV48 1.8 +RBV48 2.2+RBV48 49.3 +RBV48 51.1+RBV48 25.9 +RBV48 25.4

ALT C

SVR( )

1) 22) 03) SVR 40.9% (83 /203 )

: 2

298

129

Berg C, Goncales FL Jr, Bernstein DE, Sette H Jr, Rasenack J, Diago M, Jensen DM, Graham P, Cooksley G.

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin.

J Viral Hepat

( ): 13(7): 435-440

2006

64

51 134480kg±15kg

ALT C

SVR( )

1) 02) 53) SVR 54.7% (35 /64 )

1) (5%) (3%)2)

299

130

Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, Zeuzem S.

Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.

Gastroenterology

( ): 130(4): 1086-1097

2006

(48 vs. 72 )

455

250 20542.7 ±11.44 75.8kg

ALT 2.52±1.63IU/L( )1b

ALT C: 18 HCV-RNA1,000IU/mL ALT

130g/L120g/L 1.5mg/dL

: 1b B HIV

: 2000 12 ~2001 7: 24

SVR( )

1) 02) 61 (48 36 72 25 )3) SVR 53.2%(242 /455 ) (48 53% 72 54%)4) (48 72 )

1) (48 15.6% 72 11.1%)2)

300

131

Brandão C, Barone A, Carrilho F, Silva A, Patelli M, Caramori C, Focaccia R, Pereira L, Pedroso M, Tatsch F, Pessoa M; Pegasys Brazilian Study Group.

The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1.

J Viral Hepat

( ): 13(8): 552-559

2006

117 [(group A) 1 24 : 32 (group B) 1 48 : 31 (group C)1 24 : 54 ]

/ : 24 19 /13 48 19 /12 1 24 46 /8: 24 41.1 48 40.8 1 24 42.3: 24 73.8kg 48 76.4kg 1 24 80.7kg

ALT C: 2001 3 ~2003 8

SVR( )

1) 02) 63) SVR: group A 19% group B 48% group C 76%

3 ( ) 40%

301

132

Bronowicki JP, Ouzan D, Asselah T, Desmorat H, Zarski JP, Foucher J, Bourlière M, Renou C, Tran A, Melin P, Hézode C, Chevalier M, Bouvier-Alias M, Chevaliez S, Montestruc F, Lonjon-Domanec I, Pawlotsky JM.

Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin.

Gastroenterology

( ): 131(4): 1040-1048

2006

516

306 21046.2 ±11.570.8kg±14.8kg

ALT C: 2000 12 18 ~2003 4 9

SVR( )

1) 1 ( 0 )2) 433) SVR

1) : 12) Arm1 RNA Arm2 3

Arm1

302

133

Ciancio A, Picciotto A, Giordanino C, Smedile A, Tabone M, Manca A, Marenco G, Garbagnoli P, Andreoni M, Cariti G, Calleri G, Sartori M, Cusumano S, Grasso A, Rizzi R, Gallo M, Basso M, Anselmo M, Percario G, Ciccone G, Rizzetto M, Saracco G.A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin.


( ): 24(7): 1079-1086

2006

(RBV)+ (AMA)

161 [PEG-IFN+RBV81 PEG-IFN+RBV+AMA80 ]

/ : PEG-IFN+RBV 60 /21 PEG-IFN+RBV+AMA 59 /21: PEG-IFN+RBV50 PEG-IFN+RBV+AMA50

BMI: PEG-IFN+RBV24.9 PEG-IFN+RBV+AMA24.8

ALT C: 2001 5 ~2002 12

SVR( )

1) 1 ( )2) 43) SVR 29.6% (24 /81 )

: 1

303

134

Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, Hubmann R, Datz C, Stauber R, Steindl-Munda P, Kessler HH, Klingler A, Gangl A; Austrian Hepatitis Study Group.

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection.

J Hepatol

( ): 44(2): 275-282

2006

(RBV)+ (AMA)

209]

/ /46 /30

ALT C

SVR( )

1) 02) 13) SVR: group A 46.5%(53 /114 ) group B 51.6%(49 /95 )

1) group A 12 group B 62) group A ( )3) group A QOL

304

135

Meyer-Wyss B, Rich P, Egger H, Helbling B, Müllhaupt B, Rammert C, Gonvers JJ, Oneta C, Criblez D, Rossi L, Borovicka J, Meyenberger C, Arn M, Renner EL; Swiss Association for the Study of the Liver (SASL).

Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.

J Viral Hepat

( ): 13(7): 457-465

2006

(RBV)

219 ]

( (57%)(72%)

ALT C: 2000 11 ~2002 6

SVR( )

1) 1 ( )2) 193) SVR 53.4% (117 /219 )

: 1

305

136

Yenice N, Mehtap O, Gümrah M, Arican N.

The efficacy of pegylated interferon alpha 2a or 2b plus ribavirin in chronic hepatitis C patients.

Turk J Gastroenterol

( ): 17(2): 94-98

2006

(RBV)

74 [ ]

/ /24 /27( / /50.9 /50.85

:

ALT C

SVR( )

1) 02) 03) SVR: 48.6% 35.1%

306

137

Yu ML, Dai CY, Lin ZY, Lee LP, Hou NJ, Hsieh MY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL.

A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan.

Liver Int

( ): 26(1): 73-81

2006

(RBV)

60 45 15 ]

/ : 24 28 /17 48 11 /4: 24 45.4 48 45.1: 24 68.3kg 48 68.6kg

ALT C (1 ): 2001 9 ~2004 11

SVR( )

1) 02) 03) SVR: 24 48.9%(22 /45 ) 48 80%(12 /15 )

1)

2)

307

138

Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibrányi E, Weiland O, Noviello S, Brass C, Albrecht J.

Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia.

J Hepatol

( ): 44(1): 97-103

2006

237

127 11042.2 ( : 18-69 )71.3kg( : 44-111kg)

ALT C

SVR( )

1) 02) 25 (11%)3) SVR: 24 50%(117 /235 ) 48 71%(27 /38 )

308

139

Carr C, Hollinger FB, Yoffe B, Wakil A, Phillips J, Bzowej N, Leung J, Mirro K, Poordad F, Moore DH, Gish RG.

Efficacy of interferon alpha-2b induction therapy before retreatment for chronic hepatitis C.

Liver Int

( ): 27(8): 1111-1118

2007

+

study 1: 484study 2: 407

study1: 484 ( 331 152 ) 45.5 ±8.1study2: 407 ( 297 110 ) 48.2 ±6.7

ALT C

SVR( )

1) 02) 03) SVR: 20% 24%

5% :

309

140

Diago M, Crespo J, Olveira A, Pérez R, Bárcena R, Sánchez-Tapias JM, Muñoz-Sánchez M, Romero-Gómez M.

Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients.


( ): 26(8): 1131-1138

2007

(RBV)

72 [ 28 20g/ 24 ]

/ 21 /7 15 /5 20 /4

40.0 44.5 41.0

75.8kg 74.1kg 79.0kg

ALT C (1 )

SVR( )

1) 02) : 11% 5% 4%3) SVR: 18% 30% 38%

3

310

141

Diago M, Olveira A, Solá R, Romero-Gómez M, Moreno-Otero R, Pérez R, Salmerón J, Enríquez J, Planas R, Gavilán JC, Del Olmo J, Uribarrena R, Sillero C, Benítez A, Sánchez-Galdón S, Dalmau B, Eraña L, Montoro M, Portu J, Garijo JM, Barniol R, Domínguez A, Rota R, Olcoz JL, Antón M, Pamplona X, Casanovas T, Jiménez E, Huarte M, Díaz F, Sánchez-Ruano J, Orive M, Muñoz-Sánchez M, Roset M.

Treatment of chronic hepatitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine clinical practice in Spain: early prediction of sustained virological response rate.


( ): 25(8): 899-906

2007

(RBV)

475

319 15643.5 ±10.274.3kg±13.7kg

C (1 ): 2002 5 ~2005 5

SVR( )

1) 1 ( )2) SVR 48% (95%CI: 43.3-52.3)3) 6%(27 :

)

1) 15%[ (51%) (24%) (24%)(19%) (19%) (17%) (17%) (15%)]

2)

311

142

Kamal SM, El Kamary SS, Shardell MD, Hashem M, Ahmed IN, Muhammadi M, Sayed K, Moustafa A, Hakem SA, Ibrahiem A, Moniem M, Mansour H, Abdelaziz M.

Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response.

Hepatology

( ): 46(6): 1732-1740

2007

(RBV)

358 ) 69 ) 79) 160 ) 50 ]

( ): group A(24 ) 37 (54%) group B(36 ) 32 (40%) group C(48 ) 100(62%) 26 (52%)

: group A 41.0 group B 40.5 group C 42.2 43.2BMI: group A 28.5 group B 27.8 group C 28.6 28.9

ALT C (4 ): 2004 1 ~2006 11

SVR( )

1) 02) 03) SVR 66.8%(239 /358 ): group A 86%(59 /69 ) group B 76%(60 /79 ) group C 56%(90 /160 ) 60%(30 /50 )

312

143

Kuboki M, Iino S, Okuno T, Omata M, Kiyosawa K, Kumada H, Hayashi N, Sakai T.

Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic hepatitis C in Japanese patients.


( ): 22(5): 645-652

2007

( )

(RBV)

1) 992) 1013) 100

43

1) : 62 37 52.02) : 62 39 50.63) : 74 26 52.0

20 ALT C ( 1b)

: HBV

: 2002 6 ~2004 9

SVR( )

24 HCV-RNA (50IU/mL ) SVR

SVR RBV 61% PEG-IFN 26%(P<0.001) IFN SVR 51% IFN

50% ( RBV )RBV 19.8% PEG-IFN 15.2%

18.0% RBV 1%RBV 12.9% PEG-IFN 11.1%

(RBV ) 9%

43 PEG-IFNRBV

IFN

313

144

Marcellin P, Horsmans Y, Nevens F, Grange JD, Bronowicki JP, Vetter D, Purdy S, Garg V,Bengtsson L, McNair L, Alam J.

Phase 2 study of the combination of merimepodib with peginterferon-alpha2b, and ribavirin innonresponders to previous therapy for chronic hepatitis C.

J Hepatol

( ): 47(4): 476-483

2007

[ (MMPD)II ]

(PEG-IFN)α-2b+ (RBV)( MMPD )

PEG-IFNα-2b+RBV+ : 10PEG-IFNα-2b+RBV+MMPD25mg: 10PEG-IFNα-2b+RBV+MMPD50mg: 11

( 8 5 )

PEG-IFNα-2b+RBV+ : 8 51.4 75.8kgPEG-IFNα-2b+RBV+MMPD25mg: 7 48.5 64.8kgPEG-IFNα-2b+RBV+MMPD50mg: 3 48.4 72.0kg

C ( 1 ) 18~70 : C PEG-IFNα RBV

: 2002 5 ~2004 1

SVR( )

36 48 HCV-RNA SVR

PEG-IFNα-2b+RBV+ SVR 30% (3 /10 )PEG-IFNα-2b+RBV+MMPD25mg SVR 20% (2 /10 )PEG-IFNα-2b+RBV+MMPD50mg SVR 73% (8 /11 )

MMPDPEG-IFNα-2b+RBV

314

145

Pearlman BL, Ehleben C, Saifee S.

Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders.

Hepatology

( ): 46(6): 1688-1694

2007

( )

48 ( A): 4972 ( B): 52

( )

HCV-1 18A: 33 56 BMI 28.8B: 34 54 BMI 29.1

C (1 ) ALT 18 24

: HIV 1 HCV HBV

2003 6 ~2005 9

SVR( )

A B 24 HCV-RNASVR (PCR 10IU/mL)

A SVR 9 /49 (18%) B SVR 20 /52 (38%)(P=0.03) A 13 /22 (59%) B

5 /25 (20%)

315

146

Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, Luketic VA, Sanyal AJ.

Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha.

Hepatology

( ): 46(2): 371-379

2007

( )

(RBV)+( )

) 48)+ 49

) + 49

( )

PEG-IFN+RBV: 56% 49 82kgPEG-IFN+RBV+ 63% 48 83kgPEG-IFN+RBV( ) + 56% 45 82kg

C (1 ): HBV 1

HCV HIVChild-Pugh 6

SVR( )

72 Amplicor PCR HCV-RNA ( 25IU/mL) SVR

SVR PEG-IFN+RBV 29% PEG-IFN+RBV+ 19% PEG-IFN+RBV( ) + 49% (P<0.05) PEG-IFN+RBV 36% PEG-IFN+RBV+ 40% PEG-IFN+RBV( )+ 8% (P<0.05)

SVR

RBV( RBV )

316

147



Dig Dis Sci

( ): 52(6): 1540-1547

2007

( )

(IFN)+ (RBV)

IFN+RBV 30 29

()

IFN+RBV : 70% 45 91kgRBV : 65.5% 46 82kg

18 C (1 ):

SVR( )

24 ( 72 ) HCV-RNA SVR

SVR IFN+RBV 11 /30 (37%) 12/29 (41%) (P=0.792 )

IFN+RBV 10% 7%

IFN+RBV

317

148



Gut

( ): 56(4): 553-559

2007

( )

(RBV)( 16 24 )

16 5024 100(1 2 )

(1 3 )

16 : 32 (64%) 50.8 67.7kg24 : 58 (58%) 49.9 65.8kg

18~65 ALT C (2 ):

2 HCV HIV(Child-Pugh

B C): 2003 9 ~2005 12

SVR( )

24 HCV-RNA SVR ( 50IU/mL)

SVR 24 95 /100 (95% 95%CI: 91-99) 16 47 /50 (94%95%CI: 87-100)

24 24 3.1% 16 6%

C (2 )

SVR 243.1% 16 6%

318

149



Eur J Gastroenterol Hepatol

( ): 20(7): 680-687

2008

( IIIb )

(RBV)[ 12 12

(EVR) EVR(AMA) ]

210EVR 121 64 57 )

EVR 89 42 47 )

( 12 )

230 : 69% 42 BMI 24.6

18~65 ALT C: ( ) HBV HIV

2001

SVR( )

24 ( 72 ) HCV-RNA SVR

EVR(121 /210 57.6%) SVR 38 /64 (59.3%)2a+RBV 38 /57 (67.2%) ( ) EVR(89 /210 42.4%)SVR 7 /42 (16.7%) 15 /47(31.9%) ( P=0.07)

32 (13.9%) 20 6( 1 2 1

1 1 )

HCV 14 EVR SVR

319

150




( ): 28(1): 43-50

2008

( )

(RBV)(RBV800mg/ 1,000mg/ 1,200mg/ )

RBV800mg/ 339RBV1,000 1,200mg/ 552

RBV800mg/ : 234 (69%) 45 81kgRBV1,000 1,200mg/ : 382 (69%) 47.1 80kg

C (1 ) ( ): HCV 1

SVR( )


SVR RBV800mg/ 152 /339 (45%) RBV1,000 1,200mg/ 297/552 (54%) RBV (%) SVR

1.26 (95%CI: 1.14-1.39, P<0.001)

800mg/1,000 1,200mg/

320

151



Hepatology

( ): 47(6): 1837-1845

2008

( III )

12 19424 188

( ) 31

12 : 123 (63%) 41.5 79.8kg24 : 105 (56%) 42.0 76.5kg

18 C (2 3 ): 2 3 HCV HBV HIV

SVR( )


2 SVR 12 56% 24 82% (P=0.0057)3 SVR 12 58% 24 78%

(P=0.0015) 40

HCV-RNA15IU/mL

321

152

Napoli N, Giannelli G, Antonaci A, Antonaci S.


J Viral Hepat

( ): 15(4): 300-304

2008

[ 4 (RVR) 442 ]

44 : 1744 : 14

: 11 47.3: 10 46.9

45 C (1b ) RVR 31:

HIV

6 SVR( )

6 HCV-RNA SVR (50IU/mL)

6 SVR 16 /17 (94.1%) 13 /14(92.8%) ( )

RVR

322

153



Antivir Ther

( ): 13(5): 663-673

2008

( )

(RBV)[ ]

57 36

( 10 )

: 36 21 56 75kg1 58%

: 20 16 55.5 72kg1 78%

65 ALT C:

Child-Pugh B C F2 F3 HIV HBV HCV

: 2002 1 ~2003 12

SVR( )


SVR 25 /57 (44%) 12/36 (33%) (P=0.31) 1 SVR (PEG-IFN24% vs. IFN25%, P=0.94) 2 SVR (PEG-IFN80% vs. IFN67%, P=0.52) 3 SVR(PEG-IFN56% vs. IFN50%, P=0.89)

( )1 2

: 3 : 2 200PEG-IFN ( IFN

)

323

154

Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, Angarano G.


J Interferon Cytokine Res

( ): 28(10): 623-629

2008

( )

(RBV)

71 72

42 29 45.86 80.7kg40 32 47.82 78.9kg

( IFN+RBV ) ALT C

: 6 HCV HIV

AFP

: 2001 11 ~2007 6

SVR( )

24 HCV-RNA SVR

SVR /71 (19.7%) /72 (18.0%)

( )2b+RBV3 15% PEG-

1

PEG-IFN+RBV

PEG-IFN+RBV 20% SVR

324

155

Sood A, Midha V, Hissar S, Kumar M, Suneetha PV, Bansal M, Sood N, Sakhuja P, Sarin SK.



( ): 23(2): 203-207

2008

(RBV))

)+RBV 76)+RBV 27

( )

: 67 9 43.1 2.34: 21 6 37.3 1.64

16~70 ALT C (3 ): 3 HCV

HBV HIV( )

( )

SVR( )

24 HCV-RNA SVR

SVR 60 /76 (78.9%) 25 /27 (92.6%) (P=0.145)1

325

156

Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, Naoumov NV.



( ): 27(9): 810-819

2008

1) 12 12 24 36

2) 12 48

4512 32 12 11 24

10 36 11 12 13 48

( ) 89%

12 : 4 7 42 70kg24 : 5 5 38 69kg36 : 8 3 41 79kg

( 48 ) : 9 4 41 71kg

18~65 C (1 ): HBV HAV HIV

12 312

SVR( )

24 HCV-RNA SVR ( 20IU/mL )

12 SVR 12 5 /11 (45%) 248 /10 (80%) 36 8 /11 (73%)

12 SVR4 /13(31%)

12 24

326

157



Hepatology

( ): 48(5): 1404-1411

2008

( III )

(RBV)[ (AMA) ]

352

45

AMA : 185 167 46.3 76.7kg: 183 169 45.4 74.0kg

18 ALT C (1 )

: HIV HBV

() (QT)

: 2003 7 ~2007 2

SVR( )


SVR AMA 171 /352 (48.6%) 186 /352 (52.8%)AMA 32% 23% (P=0.01)

52 /705 (7.4%) AMA 31 288 1 ( )

AMA

327

158



Hepatology

( ): 47(6): 1884-1893

2008

( )

(24 48 2 )

24 10048 100

(1 3 )

24 : 57 (57%) 49.7 65.5kg48 : 58 (58%) 49.1 67.5kg

18~65 ALT C (1 )(

): HCV1 HBV HIV

: 2005 4 ~2007 5

SVR( )

24 HCV-RNA SVR

SVR 24 59% 48 79% (P=0.002) 2436.6% 48 12.2% (P<0.0001) 24 3% 4810% (P=0.045) 24 1 48

1

RVR 24 48

328

159



Hepatology

( ): 48(2): 407-417

2008

( IIb )

(RBV)]

1142 1 )+RBV 118

2 1 )+RBV 1104 1 )+RBV 116

8 82

: 57.9% 41.9 73.4kg2 1 ) : 55.9% 42.5 74.6kg

2 1 ) : 58.2% 41.3 76.4kg4 1 ) : 67.2% 42.7 77.3kg

ALT C (1 ):

HBV HIV

: 2005 5 ~2007 5

SVR( )


SVR 57.9% 2 1 ) 58.5%2 1 ) 55.5% 4 1 ) 50.9%

(P=0.64) 28.9% 2 1 ) 20.9% alb-2 1 ) 30.7% 4 1 ) 28.4%

(P=0.34)6.1% 2 1 )

9.3% 2 1 ) 18.2% 4 1 ) 12.1%(P=0.04) 1 ( )

IIbHCV1

2b+RBV

329

160



J Viral Hepat

( ): 16(1): 28-35

2009

( )

(RBV)[ 4 (RVR) RBV2a+RBV ]

RVR RBV 59 61

7

RVR RBV : 59% 52.73 73.06kg: 49% 52.59 70.61kg

18~70 ALT C (2 3 ): HIV

: 2005 7 ~2006 10

SVR( )

24 HCV-RNA SVR

SVR RBV 32 /59 (54%) 50 /61 (82%)(SVR 28% 95%CI: 26.5-29.5, P<0.001) RBV 27 /59 (46%) PEG-

10 /61 (17%) ( 29% 95%CI: 27.5-30.6, P<0.001) RBV

IFN RBV 63% 66%

RVR RBV )700,000IU/mL RVR

RBV

330

161

Bressler B, Wang K, Grippo JF, Heathcote EJ.


Br J Clin Pharmacol

( ): 67(3): 280-287

2009

( )

)

20 20

( )

: 12 8 47.3 99.0kg (BMI 34.0): 14 6 44.3 98.0kg (BMI 31.4)

18 (BMI 30 ) ALTC ( )

:: 2002 8 ~2004 3

SVR( )


SVR 14 /20 (70%) 15 /19 (79%)1 SVR 8 /14 (57%) 10 /14

(71%) 4

BMI 30 1

331

162



N Engl J Med

( ): 360(18): 1839-1850

2009

( IIb)

(RBV)( )

334 : 4T12PR24 ( 1224 ) 81T12PR12 ( 12 ) 82T12P12 ( 12 ) 78PR48 ( 12 ) 82

: 28

HCV 1T12PR24 : 54 46 BMI 24T12PR12 : 49 44 BMI 23T12P12 : 43 45 BMI 24PR48 : 46 45 BMI 24

18~65 ALT C (1 ): 2

2006 8 2 ~2007 1 17

SVR( )SVR: HCV-RNA :


0 0 SVR 46.3%(38 /82 )SVR T12PR12 T12P12 48% PR48( ) 46%

T12PR12 SVR60% T12P12 SVR36% (P=0.003)T12PR24 SVR69% PR48 (P=0.004)

Grade3 3~7%T12PR12 T12PR24 7% 12

3.0g/dL 3.1-3.9g/dL

12% 7%

HCV 1 T12PR24PR48 SVR RBV SVR

332

163

Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, Sata M.


Am J Gastroenterol

( ): 104(1): 70-75

2009

[ 44 ( 68 ) ]

113 ( 56 57 )

1b: 26 30 55.3 BMI 23.1: 30 27 54.6 BMI 23.4

20~75 ALT C (1b ): HBs

80,000/ 3

2,500/mL 12g/dL: 2005 1 ~2006 6

: 24

SVR( )


SVR 20 /56 (36%) 30 /57 (53%)(P=0.07) 16~24 SVR

1 /11 (9%) 7 /9 (78%) (P=0.005)7 /56 (12.5%) 6 /57 (10.5%)

(P=0.78)

SVR 30% 60%44

333

164



Ann Intern Med

( ): 150(8): 528-540

2009

( )

(RBV)A ×12 ×60 72B ×12 ×36 48C ×72 72D ×48 48

942 (A 317 B 156 C 156 D 313 )

: 106

A : 64% 48.1 81.5kgB : 60% 48.8 81.1kgC : 69% 49.4 81.2kgD : 68% 48.5 80.9kg

18 ) C ( ): A B HIV HCV

6

: 2003 9 ~2005 4 : 2007 2

SVR( )


SVR A 52 /317 (16%) B 11 /156 (7%) C 22 /156 (14%) D 27 /313(9%) A D ( ) 1.8 (95%CI: 1.32-3.02,

P<0.001) SVR 12 A+B 21% C +D 13% 12 SVR49%(77 /157

) 12 4%(32 /719 )A 37 (12%) B 6 (4%) C 18 (12%) D 20 (6%)

1 ( )72 (A +C ) 48 (B +D ) (P=0.002)

) C ( )) SVR

12

334

165




( ): 24(3): 366-371

2009

( )

(RBV))

53 26 27 )

6 ()

24 (57 55 ) 57kg

20 ALT C (2 ): IFN

: 2006 2 ~2007 10

SVR( )

24 HCV-RNA SVR

SVR 10 /26 (38.5%) 20 /27 (74.1%)(P=0.013) 2 /26 (7.7%) 2 /27 (7.4%)

1 11 3

2 C

335

166


Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients.


( ): 30(4): 352-363

2009

( )

(RBV)[ (AMA) AMA ]

AMA 316AMA 314

( 37 )

AMA : 189 127 43.74 73.02kgAMA : 173 141 45.48 73.12kg

18 ALT C ( ): 6

HCVHAV

SVR( )


SVR AMA 193 /316 (61.1%) AMA 192 /314 (61.1%)(P=1.000) AMA 79 /316 (25%) AMA 88 /314 (28.03%)

(P=0.417)

AMA

336

167

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, LeeWM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K,Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS; IDEAL Study Team.


N Engl J Med

( ): 361(6): 580-593

2009

( )

(PEG-IFN)α+ (RBV)(PEG-IFNα-2b PEG-IFNα-2b PEG-IFNα-2a )

3,070 : 3PEG-IFNα-2b (PEG-IFNα-2b 1.5μg/kg/ RBV800~1,400mg/ ) 1,019PEG-IFNα-2b (PEG-IFNα-2b 1.0μg/kg/ RBV800~1,400mg/ ) 1,016PEG-IFNα-2a (PEG-IFNα-2a 180μg/ RBV1,000~1,200mg/ ) 1,035

118

40 18.6% 83.4kg( 3 )PEG-IFNα-2a PEG-IFNα-2b 1 RBV

18 HCV 1 HCV-RNA HCV1,500/ 3 80,000/ 3 12g/dL

( ) 13g/dL ( ): HIV HBV (

>8.5%) ( >125kg): 2004 3 ~2006 6

: 24

SVR( )RNA (SVR: 24 HCV-RNA ) (

HCV-RNA )

24 HCV-RNA SVR ( 27IU/mL): WHO grading system

SVR 3 : PEG-IFNα-2b 39.8% PEG-IFNα-2b38.0% (2 P=0.20, 1.8%, 95%CI: -2.3 - 6.0) PEG-IFNα-2a 40.9%(PEG-IFNα-2b P=0.57, -1.1%, 95%CI: -5.3 - 3.0) PEG-IFNα-2b

23.5%(95%CI: 19.9-27.2) PEG-IFNα-2b 20.0%(95%CI: 16.4-23.9)PEG-IFNα-2a 31.5%(95%CI: 27.9-35.2)

: 8.6~11.7% 2.1~5.9%

2.1~3.8% 1.8~2.6% 12 2 ( )

HCV 1 3 SVR

337

168


Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial.

Hepatology

( ): 50(4): 1045-1055

2009

( )

(RBV)( 12

)

(12 ) 433 438

(12 ) : 298 135 43.6 77.3kg: 285 153 43.3 78.7kg

18~75 ALT C (1 ): 1 HBV HIV

HCV 6

: 2004 8 2006 ( : 2004 9 ~2007 2)

SVR( )


SVR (12 ) 230 /433 (53%) 219 /438 (50%)(P=0.29)

(12 ) 105 /431 (24%) 112 /435(26%) (12 ) 46 /431 (11%) 45 /435(10%) 1

(12 ) 119 /433 (27%)45 /438 (18%)

C (1 ) 12

12 SVR

338

169

Rossignol JF, Elfert A, El-Gohary Y, Keeffe EB.

Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide,peginterferon, and ribavirin.

Gastroenterology

( ): 136(3): 856-862

2009

( )

(PEG-IFN)α-2a+ (RBV)PEG-IFNα-2a+RBV 48 (PEG-IFN+RBV )

(NTZ) 12 PEG-IFNα-2a+NTZ 36(PEG-IFN+NTZ )NTZ 12 PEG-IFNα-2a+RBV+NTZ 36 (PEG-IFN+RBV+NTZ )

3

PEG-IFN+RBV 40PEG-IFN+NTZ 28PEG-IFN+RBV+NTZ 28

2

PEG-IFN+RBV : 36 4 40 BMI( )28PEG-IFN+NTZ : 25 3 37 BMI( )27PEG-IFN+RBV+NTZ : 27 1 37 BMI( )25

18 ALT C (4 ): IFN HBV

: 2006 8 ~2008 2

SVR( )

24 Abbott m2000(lower limit of detection=12IU/mL) Bayer Versant v.3.0(lower limit of detection=615IU/mL) SVR

1) SVR PEG-IFN+RBV 20 /40 (50%) PEG-IFN+NTZ 17 /28 (61%) PEG-IFN+RBV+NTZ 22 /28 (79%) PEG-IFN+RBVPEG-IFN+NTZ PEG-IFN+RBV+NTZ(P=0.023)2) PEG-IFN+RBV 1 PEG-IFN+NTZ

1 8 (PEG-IFN+RBV 5 PEG-IFN+NTZ 3 ) 11

(PEG-IFN+RBV 5 PEG-IFN+NTZ 4 PEG-IFN+RBV+NTZ 2 )

C (4 ) 12 NTZ 36 PEG-IFNα-2a+RBV+NTZ

339

170

Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S, McHutchison JG; MErimepodib TRiple cOmbination Study Group.


Hepatology

( ): 50(6): 1719-1726

2009

( IIb )

(RBV)(MMPD)50mg 100mg

3 ]

117MMPD50mg 119MMPD100mg 118

62

: 69.2% 50.0 89.7kgMMPD50mg : 60.5% 48.9 88.2kgMMPD100mg : 64.4% 49.3 85.5kg

18~70 ) C (1 ) (12 12 2-log 24

HCV-RNA ): RBV

: 2004 7 ~2006 10 (METRO Study)

SVR( )

24 HCV-RNA SVR ( 30IU/mL10IU/mL)

SVR MMPD50mg 6 /107 (6%) MMPD100mg 5 /112 (4%) 5/104 (5%) (P=0.8431)

MMPD50mg 4 MMPD100mg 6 5

C (1 )+RBV+ MMPD MMPD

340

171



Liver Int

( ): 29(1): 120-125

2009

(RBV)[ 4 (RVR) 8 24

]

RVR 8 15RVR 24 17( RVR 24 28 )

24 37 56.7 / =40 /21 59.1kg

C (2 )2006 1~6

SVR( )

6 HCV-RNA SVR

RVR 32 /60 (53.3%) SVR RVR 8 5 /15 (33.3%)RVR 24 14 /17 (82.4%) (P=0.0140)RVR 24 SVR15 /28 (53.6%)

2C (2 )

RVR 8

341

172



Gastroenterology

( ): 138(1): 116-122

2010

( )

(RBV))

160 160

( )

: 81 79 51.3 70.4kg: 94 66 48.9 69.9kg

18 ALT C (1~4 ):

HBV HIV HCV

2004 3 ~2006 12

SVR( )

24 HCV-RNA SVR ( 50 IU/mL)

SVR 110 /160 (68.8%) 87 /160 (54.4%)(P=0.008) HCV-RNA (500,000IU/mL

)26 /320 (8.6%) 1 4 3

/93 (3.2%) 13 /93 (14%) 2 3 1/67 (1.5%) 9 /67 (13.4%)

()

( )

342

173

Brady DE, Torres DM, An JW, Ward JA, Lawitz E, Harrison SA.


Clin Gastroenterol Hepatol

( ): 8(1): 66-71.e1

2010

( )

( 12g/kg 12 )

610 ( 299 311 )

46

: 49.7% 45 84.5kg: 50.3% 45 84.87kg

ALT C (1 4 ) (Child-Pugh A):

HCV 1 4Child-Pugh A

(HBV) HIV

12

62002 3 ~2005 3

SVR( )

24 HCV-RNA SVR

SVR 96 /299 (32%) 92 /311 (29%)(P=0.434) ( )

2

SVR12%12 C (1 4 )

343

174

Khattab M, Emad M, Abdelaleem A, Eslam M, Atef R, Shaker Y, Hamdy L.


Liver Int

( ): 30(3): 447-454

2010

( )

(RBV)[ ( ) ]

48 49

: 14 (29.2%) 40 BMI 28.63: 15 (30.6%) 37 BMI 28.4

18 C (4 ) : AHA

HBV HIV 6

: 2007 2 ~2009 4

SVR( )

24 HCV-RNA SVR ( 12 IU/mL)

SVR 29 /48 (60.4%) 19 /49 (38.7%)(P=0.04)

3 4

SVR

344

175


Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BMC Gastroenterol

( ): 10:21

2010

[ 4 (RVR) 1224 ]

12 7224 71

RVR 24 67

RVR: 116 (81%) 42 BMI 24RVR: 54 (80%) 45 BMI 25

ALT C (2 3 )

: 6HIV HBV HCV

: 2006 7 ~2008 1

SVR( )


SVR 12 60 /72 (83%) 24 53 /71 (75%)RVR SVR33 /67 (49%)

12 0 /72 (0%) 24 5 /71(7%) RVR 7 /67 (10%)

C (2 3 ) 4 (RVR)12 24

SVR

345

176



Dig Dis Sci

( ): 55(9): 2629-2635

2010

(RBV)[ (AMA) ]

63 61

: 26 37 46.2 70.41kg: 29 32 44 74.43kg

ALT (1 ) ( ): HCV HIV HBV

: 2003 3 ~2005 6

SVR( )


SVR 25 /63 (39.7%) 26/61 (42.6%) (P=0.561)

5 /63 (7.9%)2a+RBV+AMA 6 /61 (9.8%)

AMA AMA

346

177

Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E, RussoA, Colombo M.

Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plusribavirin in chronic hepatitis C.

Gastroenterology

( ): 138(1): 108-115

2010

( )(

)

(PEG-IFN)α-2a+ (RBV)PEG-IFNα-2b+RBV

PEG-IFNα-2a 212PEG-IFNα-2b 219

( )

PEG-IFNα-2a : 128 (60.4%) 51.6 72.2kgPEG-IFNα-2b : 120 (54.8%) 52.8 68.9kg

18~70 ALT C (1~4 ): ALT ( : 12g/dL 13g/dL

) 2,500/ 3 1,500/ 3 75,000/ 3

1.5 HIV IFNRBV

: 2003 9 ~2007 6

SVR( )


SVR PEG-IFNα-2a 140 /212 (66%) PEG-IFNα-2b 119 /219 (54%)(P=0.02) 1 SVR PEG-IFNα-2a 44 /91 (48%) PEG-IFNα-

2b 28 /87 (32%) (P=0.04) 2 SVR PEG-IFNα-2a66 /69 (96%) PEG-IFNα-2b 61 /74 (82%) (P=0.01)3 SVR PEG-IFNα-2a 22 /34 (65%) PEG-IFNα-2b 22 /32 (69%)

(P=0.9) 4 SVR PEG-IFNα-2a 44% PEG-IFNα-2b31% (P=0.5)

PEG-IFNα-2a 1% PEG-IFNα-2b 1%PEG-IFNα-2a 18 (8%) PEG-IFNα-2b 23 (11%) (P=0.6)

PEG-IFNα-2a+RBV PEG-IFNα-2b+RBV

347

178

, , , , , .

C.

( ): 52(Suppl1): A157

2011

(PEG-IFN)+ (RBV)

20,072

PubMed EMBASE Cochrane Library

PEG-IFN+RBV

SVR( )

SVR5.19%(95%CI: 4.87-5.52)

33 0.17%(95%CI: 0.12-0.24)0.043%(95%CI: 0.018-0.084)

348

179Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med

( ): 351(15): 1521-15312004

( )( ) HBe

(LMV) 1 HBe

LMV

B LMV100mg/

651 (LMV 436 215 )

: 41

LMV : 370 (85%) 43 Child-Pugh 5(78%) 6(17%) 7 (5%)4(40%) 5(29%) 6(31%)

: 182 (85%) 44 Child-Pugh 5(73%) 6(19%) 7 (8%)4(35%) 5(26%) 6(39%)

: 6 HBs HBe HBs HBV-DNA4

: ( AFP ) ALT (10 )HCV HDV HIV (

) 28g/dL 1,500/ 3 50,000/ 3

6 LMV

: “ ”“ ” Child-Pugh 2

(HCC)

1 3 3HBe HBe AFP

6 HBs HBs 1HBs 2 HBs 1

12 24 36 48 60 HBV-DNA YMDDPCR-RFLP

YMDD

72 : LMV 7.8%(34 /436 ) 17.7%(38 /215 ) (HR: 0.45, P=0.001) Child-Pugh : LMV 3.4%(15 ) 8.8%(19 ) (HR: 0.45, P=0.02) HCC : LMV 3.9%(17 ) 7.4%(16 ) (HR: 0.49, P=0.047) 1

HCC HCC HR: 0.47, P=0.052LMV 49% YMDD Child-Pugh

(7%, <1%)LMV 2 [ ( )1 1 ]

14 (HCC8 6 ): LMV 12%(54 ) 18%(38 )

12 LMV 12 4

B LMVHR0.45 (95%CI: 0.28-0.73)

349

180

Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, Wong BC, Fung J, Yuen JC, Lai CL.

Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease.

Antivir Ther

( ): 12(8): 1295-1303

2007

HBe (LMV) ( >3.5g/mL <1.5×ULN)

LMV 142 124

LMV : 106 36 33.9 (20.2-54.4 ): 90 34 33.4 (20.8-59 )

HBe LMV 20g /

: 1994 6 ~1997 8 31 3: 1994 6 1 ~1997 8 31

60

3~6 HBV

LMV(P=0.005) YMDD ( 8 76.3%) YMDD

LMV YMDD LMVHBV-DNA HBe YMDD

(P=0.024)HBV-DNA (P=0.001)

LMV

350

181

Papatheodoridis GV, Dimou E, Dimakopoulos K, Manolakopoulos S, Rapti I, Kitis G, Tzourmakliotis D, Manesis E, Hadziyannis SJ.

Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine.

Hepatology

( ): 42(1): 121-129

2005

(LMV)

LMV 201 209

195

( 4 )

LMV : 167 52 31.8%: 174 47 27.3%

: 160 49 34.9%

HBe B HBs HBV-DNA(Child-Pugh A)

: HCV HDV HIV6

LMV HBV: 1997 1 ~2001 12

3 6 HBV-DNA6 AFP

LMV (P=0.11)(P=0.68)

(P=0.036) (P=0.04)LMV (P=0.10)

(P=0.65)(P=0.02) (P=0.03)

ALTHBe B

LMV

351

182


Comparison of Interferon and Lamivudine Treatment in Japanese Patients With HBeAg Positive Chronic Hepatitis B.

J Med Virol

( ): 79(9):1286-1292

2007

(LMV) (100mg/ ) (IFN)

327IFN 179LMV 148

IFN (35 ): 101 18 28 [ ] 73 /28 / 15LMV (35 ): 97 20 28 [ ] 47 /22 / 4IFN (35 ): 46 14 43 [ ] 17 / 29

/ 15LMV (35 ): 29 12 42 [ ] 12 /15 / 7

: 6 ALT ( 2 ) 1HBe

HCV: HCV HBV ( )

1990~2004

HBe

1~3 HBe

HBe IFN : (35 ) 2 31.1% 6 70.0% (35) 2 19.0% 6 47.1% (P=0.002) LMV : (35

) 2 36.8% 6 62.8% (35 ) 2 27.4% 6 50.4%(P=0.477) IFN LMV HBe

OR: 1.14(95%CI: 0.84-1.54) (P=0.410): (IFN) (LMV)

4(P<0.001)

LMV IFN

352

183

Shamliyan TA, MacDonald R, Shaukat A, Taylor BC, Yuan JM, Johnson JR, Tacklind J, Rutks I, Kane RL, Wilt TJ.

Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference.

Ann Intern Med

( ): 150(2): 111-124

2009

93 60 (RCT) HBe20~1,367

1990~2008 BRCT 50 24

B : 78% 64% 30%

MEDLINE PubMed Cochrane Library 1989B RCT

HBe HBsHBV-DNA ALT

: HBeHBs HBV-DNA ALT

1) 16RCT(4,431 ) B

2) 60RCT HBsALT HBe

-2b HBe ALTHBe ALT

HBe ALT3)

B

5

355

184Tramarin A, Gennaro N, Compostella FA, Gallo C, Wendelaar Bonga LJ, Postma MJ.

HCV screening to enable early treatment of hepatitis C: a mathematical model to analyse costs and outcomes in two populations.

; ( ): Curr Pharm Des; 14(17): 1655-16602008

(1) 9,460 (2) 4,738,313( 340,783 )

HCV ( 6 HCV6 2 HCV

)

( 32 ) ( 42 ) 2HCV

( 32 ) (42 ) 2 82 77

( 40~50 )

22RCT

QOL 26 27 28

National Tariffs System ( 50%)

3%

-28,300,000 (1 =120-3,396,000,000 ) 9,036QALY - -3,132/QALY (-375,840 /QALY)

904,650,000 (108,558,000,000 ) 993QALY- 918,147 /QALY (110,177,640 /QALY)

100%( 100%)

100%

356

HCV2.2%

0.014%0.05%

HCV 16%HCV 84%

30%SVR 85%

24%1,4SVR 42%

2,3SVR 79%

99%

2%

(1 ) 4,092

( ) 510,000

( ) 9,777,840

( ) 137,640( ) 137,640

357

185Nakamura J, Terajima K, Aoyagi Y, Akazawa K.Cost-effectiveness of the national screening program for hepatitis C virus in the general population and the high-risk groups.

; ( ): Tohoku J Exp Med; 215(1): 33-422008

HCV

ALTHCV (HCV HCV HCV-PCR )

5

40~70 (99,001 ) 40(42,538 )

30

1Berg(2006) 2 3 Shiffman(2007) 2004

3%

SVR 95%CI50% - +50% 50% - 100%

40 14.74 ( ) 17.39 () 70 10.89 ( ) 12.13 (

) 40 14.74 ( ) 17.39 () 60 12.02 ( ) 13.55 (

)30 40 692,900 70172,500 (1 =100 ) 40 269,700 60

160,70040 5,740,900 ( ) 5,965,700 (

) 70 3,762,200 ( ) 4,364,000 () 40 5,740,900 ( )

5,542,500 ( ) 60 4,294,800 ( )4,645,600 ( )

- 4084,800 /QALY 70 480,000 /QALY 40-74,900 /QALY 60 230,000 /QALY

+( 100%)

HCV (0.36% 0.81%) 2Table 4 40 5,740,000

Fig.2

QALY

358

HCV0.36%0.81%

1 SVR 50%2 3 SVR 71%

6.5%2.9%

(HCC)HCC 1.4%HCC 7.3%HCC 7.3%

15.3%

19.4%

HCV 1,020HCV 2,040HCV-PCR 3,060

359

186Loubière S, Rotily M, Moatti JP.Prevention could be less cost-effective than cure: the case of hepatitis C screening policies in France.

; ( ): Int J Technol Assess Health Care; 19(4): 632-6452003

CHCV (EIA) HCV-RNA (PCR) +

4 (1)HCV HCV (2) HCV (3) EIA 2 EIA (4) EIA

PCR < 1 >

(1) (IDUs) (2) 1991 (3)

( )

3% (±50% )

22.4422.46 22.47

16.5917.56 17.88

6.7076.719 6.720

1 290 (1100 29,000 ) 363 (36,300 )

400 (40,000 ) 1563 (56,300 )

782 (78,200 ) 1,149(114,900 ) 1

17,641 (1,764,100 )22,125 (2,212,500 ) 23,566 (2,356,600 )

- 4,102 / (410,000 / )18,054 / (1,810,000 / )

(EIA+PCR) -5,821 / (580,000 / ) 283,495 /

(28,350,000 / )

(EIA+EIA) - 4,513 / (450,000 / )(EIA+PCR) - 5,778 / (580,000 / )

( )50% 40%

HCV

360

70%30%

HCV (EIA)97.2%99.7%

HCV-RNA (PCR)99.9%99.8%

SVR 33%

HCV80%

7%1.2%

( )3.5

361

187

Singer ME, Younossi ZM.

Cost effectiveness of screening for hepatitis C virus in asymptomatic, average-risk adults.

; ( ): Am J Med; 111(8): 614-621

2001

HCV

(1) ELISA+PCR (2) PCR (3)

(/QALY)

35

3%

95%CI~2

23.596QALY 0.002QALY

1 390 (1 100 39,000 )ELISA+PCR 511 (51,100 ) PCR 572 (57,200 )

45 (12%)( ) ELISA+PCR 28 (5%)

71 (14%) ()

QALYC

(0.02 )0.0150%

C (ALT 0.02 ALT0.01)

1 HCV0.5% 61 20%

( 0.5% 0.6%)

20% 12/3

100% 20%

362

35 HCV 2.9%

HCV 1 72%

ELISA98.6%

99%

RNA PCR100%100%

0.5%C

(ALT ) 1%

(ALT ) 0.2%

0.5%

3.9%1.4%

1.4%3.1%

12.9%

42.7%

1 21% 1 5.7%

1 37%2 3 89%

363

188

C .

; ( ): ; 46(6): 447-465

1999

-

HCV -

HCV ( PHA ) 3

HCV (IFN) 30

-

30~59 56,746

IFN

( )

( )

3%

1,071,410,000 (1 18,881 )1,830,940,000 (1 32,266 ) - 1.71

1,337,570,000 (1 23,571 ) 2,849,910,000(150,222 ) - 2.13

- 2.32 1% - 1

IFN

(35% )IFN

3

- (WTP)

8.3%( 5.1% )IFN

364

IFN1,220,000

CR 29.8%

C2%

53%

87%

40% 10% 5% 1%

11 50%8 50%

3.5 100%

HCV 8.3%

5.1%

1,800 ~2,700

107,00015,000

IFN 1,975,000

30

10

20

365

189

Jusot JF, Colin C.

Cost-effectiveness analysis of strategies for hepatitis C screening in French blood recipients.

; ( ): Eur J Public Health; 11(4): 373-379

2001

HCV

EIA ALT HCV-RNA

HCV(1)40 EIA (2)40~65

EIA (3) EIA ( 2 )ALT (2 2 3 2 ) 3

30

EIA HCV-RNAMEDLINE

95%CI

12

1) 1,681.95 (1 =1728,593 ) 40 6,594.55 (112,107 )2) 40 0.0085 ( 3 )0.0004 ( 3 )3) - 40 776,474 / (13,200,000 /

) 2,636,500 / (44,820,000 / )800,191 / (13,600,000 / )

HCV

366

HCV1.2%

1991 3%

70%

2%1.2%

IFN SVR 35%IFN 1.2%

5.6%0%5%3%

ALT50%90%

EIA97%99%

HCV-RNA99%

99.9%

367

190

Saab S, Brezina M, Gitnick G, Martin P, Yee HF Jr.

Hepatitis C screening strategies in hemodialysis patients.

; ( ): Am J Kidney Dis; 38(1): 91-97

2001

ELISA ALT SIA PCR

ELISA ALTELISA 2

PCR 2

5,000 5

1992~2000 MEDLINEHCV

C (5 )

( ) 0.53

1 382 (1 10038,200 ) 195 (19,500 )

696 (69,600 )44 85

5,000 9% HCV

368

HCV 9%HCV 0.2%

HCV 1.4

ALT83%90%

ELISA SIA93%84%

ALT 631ELISA 2,030

SIA 5,830PCR 7,420

369

191

Leal P, Stein K, Rosenberg W.

What is the cost utility of screening for hepatitis C virus (HCV) in intravenous drug users?

; ( ): J Med Screen; 6(3): 124-131

1999

HCV

ELISA+PCR (100% 99.6-99.8%) HCV

(/QALY)

MEDLINE HealthStar Embase National Research Register

( 62 )

19975,600 687,787 (1 150103,170,000 1 18,423 )

6%

43QALY (2QALY ) 9,300/QALY(1,400,000 /QALY)

3 (0.5%)

80% 44% 50%3 55% 9 50%

HCV 60%IFN

370

24 SVR 35%48 SVR 43%

5,600HCV 3,360

( ) 60%

2,688

( ) 80%

ELISA99%

99.6%

PCR1,601

RNA 1,441( ) 90%

634( ) 44%

21

50%3 55%

9 50%

3 SVR 53%

SVR 29%

50%

371

192

Veldhuijzen IK, Toy M, Hahné SJ, De Wit GA, Schalm SW, de Man RA, Richardus JH.

Screening and early treatment of migrants for chronic hepatitis B virus infection is cost-effective.

; ( ): Gastroenterology; 138(2): 522-5302010

( ?)HBV (

) 1HBV (HB HBs HBe HBe

ALT )HBV ( ) 1

HBe ALT

(/QALY)(15 65

) 8%(1,300,000 ) ( 3.35% 44,117 HBs)

B

35% 58% 75%44

( ) QALY

Dutch Healthcare Authority (DPG )Dutch Health Care Insurance Board

3%(

)4% 1.5%

1) 1,310,000 159,300,000 (1 120 7,116,000,000 )

B ( 173 )652 108/1,073 (10%) 6,614QALY

2) 8,966 /QALY (1,075,920 /QALY) HBV

7,936 /QALY (952,320 /QALY) 11,705 /QALY (1,404,600/QALY) 3) 5,568 /QALY (668,160/QALY) 60,418 /QALY (7,250,160 /QALY)

(1) (2) (3)

3 35%58% 75%

1(

) ()

372

HBe

SVR 22%0.2%

HCC 0.2%

HBe

SVR 11%0.6%

HCC 0.2%

HBe

SVR 27%0.2%

1%

HBe

SVR 11%0.6%

1%

3.3%HBV 26%

HCC 1.2%HCC HBV 35%

HBV 6.6%

HBV 3.35%

373

193

Kang JY, Lee TP, Yap I, Lun KC.

Analysis of cost-effectiveness of different strategies for hepatocellular carcinoma screening in hepatitis B virus carriers.

; ( ): J Gastroenterol Hepatol; 7(5): 463-468

1992

HBV 30 (US) AFP

US AFP

(3cm )

30 HBV

( )

(1975 ~1989 3 MEDLINE )

( )

(3cm )

10 US US AFP90% 1 11,800 (1,180,000 )

(1 =100 )

4

374

30 HBV0.927%

AFP68.0%19.9%

( 1cm)87.8%98.1%

1~3cm 1.63

AFP 3,00010,000

CT 207,500

375

194

Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, Jackson S, Ryder S, Price A, Stein K.

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

; ( ): Health Technol Assess; 11(34): 1-206

2007

-

NHS(National Health Service) ( ) (HCC)

(1)AFP (US) (2)AFP (AFP) (3) ( ) 6 1

-

(ALD) HBV HCV

70

EQ-5D SF-36

NHS National Schedule of Reference Costs (NSRC)

3.5%

HCC 1 (NNS)1 AFP 19 US 20 AFP+US 15

6 AFP 13 US 13 AFP+US 1126,900 (1 =150 4,035,000 )

9.021QALY AFP 1,500 (225,000 )0.075QALY - 20,700 /QALY(3,105,000

/QALY) AFP 6 AFP1,000 (150,000 ) 0.035QALY -

27,600 /QALY(4,140,000 /QALY) 6 AFP6 AFP+US 1,000 (150,000 )

0.017QALY - 60,100 /QALY(9,015,000/QALY)

100% 2(1)50% 5%

(2)75% 10%

NHS 30,000 /QALY HBV6 AFP+US HCV 6 AFP

376

ALD 57.6%HBV 7.3%HCV 35.1%

ALD 3.3%HBV 3.3%HCV 3.3%

ALD 1.7%HBV 2.2%HCV 3.7%

(2 ) 127

AFP

20 35.2%21-400 56.8%

400 8%

20 37.8%21-400 50.0%

400 12.2%

20 22.2%21-400 44.4%

400 33.4%

21-400 8.8%400 0.6%

10.7%28.6%75.0%

(1- ) 3.50%

CT( ) 100%

(1- ) 10.2%

377

195

Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U.

Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus-related cirrhosis.

; ( ): Clin Gastroenterol Hepatol; 3(1): 75-84

2005

HCV

AFP (6 70 )

6 AFP( 5cm

)

45

45 80 ( )

1980~2003 MEDLINE (HCV

) AFP 79% 87%2cm 0% 5cm 100%

QALY( )

3%

( )

( ) 45 HCVQALY 14.75 QALY 53,200 (5,320,000 1 100 )

15.24 QALY (0.49 QALY ) 63,500 (6,350,000 ) 26,100 /QALY (2,610,000 /QALY)

17.33 QALY (2.58 QALY ) 173,500 (17,350,000 ) 46,700

/QALY(4,670,000 /QALY)18.56

QALY (3.81 QALY ) 245,400 (24,540,000 ) 50,400/QALY (5,040,000 /QALY)

( )

378

4%

2%

2%23%

20%70%

AFP+79%87%

AFP 2,30023,000

CT 62,000

379

196

Nakamura J, Toyabe S, Aoyagi Y, Akazawa K.

Economic impact of extended treatment with peginterferon alpha-2a and ribavirin for slow hepatitis C virologic responders.

; ( ): J Viral Hepat; 15(4): 293-299

2008

72

( )

HCV 1 43 HCV-RNA ALT30

2007 3 MEDLINE

30 ( )

(48 )

1)

2) ( )

3%

(SVR )

1) QALY( ) 48 14.80 QALY 7215.35 QALY 0.55QALY 48 71,559 (7,160,000 )

72 69,438 (6,940,000 ) 2,762 (280,000 )( -500,000 /QALY)2) 72

380

SVR48 17%72 29%

6.5%1.4%

2.9%7.3%

7.3%3.1%

15.3%

19.4%

13.6%2 5.2%

381

197

Nakamura J, Kobayashi K, Toyabe S, Aoyagi Y, Akazawa K.

The cost-effectiveness of the new protocol reflecting rapid virologic response to peginterferon alpha-2b and ribavirin for chronic hepatitis C.

; ( ): Eur J Gastroenterol Hepatol; 19(9): 733-739

2007

4 (RVR)

45 30

31 1,070 1993 20032006 MEDLINE

30 ( )

( )

3%

[SVR( ) RVR]

1 ( ) 13.35QALY 13.68QALY0.33QALY 44,599 (1 1205,350,000 ) 38,606 (4,630,000 ) 5,993

(720,000 ) ( - -2,180,000 /QALY)

2 3 13.74QALY 13.76QALY0.02QALY 34,005 (4,080,000 )

31,154 (3,740,000 ) 2,851 (340,000 )( - -17,110,000 /QALY)

SVR

SVR

382

148 SVR 37%

124 SVR 89%

148 SVR 64%

1 SVR 75%

2 312 SVR 85%

2 324 SVR 60%

2 3 SVR 76%

148 SVR 48%

148 SVR 71%

2 324 SVR 76%

6.5%1.6%

8.5%8.3%

8.3%12.9%

20%

13.6%2 5.2%

383

198

Hayashida K, Nagasue I, Fukuda T, Gunji A.

The natural history model of hepatitis C virus infection and the economic evaluation of alpha interferon treatment.

; ( ): J Epidemiol; 12(1): 22-32

2002

HCV

(IFN) 600MIU

IFN

1) 2) (HCC) 6

1995

5%

HCC IFN C HCCC 55~59

IFN 20 18,612 (1 100 1,860,000) 30 14,818 (1,480,000 ) 40 8,440 (840,000 ) 50 -2,136 (-

210,000 ) IFN20 49,747 / 30 39,072

/ 40 22,582 / 50 5,884 /IFN

IFN

384

540.8%

TAE( ) 8%0%

16.5%

33.4%TAE 35.5%

31.1%

5 19.4% 5 15.9%

5 14% 5 6.24%

HCV 5 0.26%

1936~40 5 0.36%1941~45 5 0.29%1946~50 5 0.23%1951~55 5 0.18%

HCV 5 11%

5 P = 1/[1 + exp ( -1273 t + 4.6725) ]5 P = 1/[1 + exp ( -0.0456 t + 4.739 ) ]

IFNCR( ) 35.7%

11.9%

385

199

Ishida H, Wong JB, Hino K, Kurokawa F, Nishina S, Sakaida I, Okita K, Tamesa T, Oka M, Torimura T, Sata M, Takahashi S, Chayama K, Inoue Y.

Validating a Markov model of treatment for hepatitis C virus-related hepatocellular carcinoma.

; ( ): Methods Inf Med; 47(6): 529-540

2008

HCV : (HR) (LAT)(TACE) (HAIC)

HR LAT TACE HAIC

( )

( 3 ) 65 62% 89%( )

1994 1 ~2003 12 3793

5 HR 66%60% LAT 74% 64% LAT + TACE 44% 38% TACE 34% 31% HAIC 24%

26%

100%10%

386

C7.3%

6%

0.8%

0.1%

HCC

9%

45%

45%

HCC ( HCC 1 )

32%

37%

22%

18%

HCCLAT+TACE 60%

LAT+TACE 6%

7%

TACE 21%29%

HCCHAIC 17%

33%

肝炎ウイルス･肝がん検診 - ncccanscreen.ncc.go.jp/evidence/kan_ev_report.pdfp : ã Ò...

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