ودرمان تشخيص هاي تازههپاتيت

هپاتيت • جهاني روز برنامهدرمان • و بهداشت شبكه

شهريار•12/5/1393

هاي هپاتيت باليني تشخيصويرال

- ) بررسي ) و دار عالمت يرقان علل افتراق گروه دو در) عالمت ) بدون اپيدميولو‍ژ-يك

- - و باليني معاينه دقيق حال شرح با بايد يرقان با گروه درسونوگرافي عمدتا كه برداري تصوير و آزمايشگاهي بررسي

هاي يرقان و ها دارو برخي كبدي سميت مانند ديگر علل است – - وهموليتيك- ايمون اتو عفوني غير هاي بيماري انسدادي

سيستميك هاي عفونت و كبد گير فضا و انفيلتراتيو ضايعاتتيفوييد – – ها سمي سپتي مانند يرقان با همراه گاهي

رد ما كشور در كنگو و كريمه تب ولپتوسپيروزو بروسلوزشوند.

مادر - بخصوص خانواده در بيماري سابقه عالمت بدون گروه دربهداشتي– – – غير هاي خالكوبي آلوده تزريقات سابقه

- براي پرخطر هاي رفتار اعتيادو غيرمجاز هاي دندانپزشكيكنند مي راهنمايي هپاتيت بررسي آزمايش

Causes of Acute Hepatitis

Causes of Chronic Hepatitis

Abbreviations :NAFLD: nonalcoholic fatty liver disease; AIH: autoimmune hepatitis; PBC: primary biliary cirrhosis

PSC: primary sclerosing cholangitis, A1AT: alpha-1 antitrypsin deficiency, HHC:hereditary hemochromotosis

هپاتيت آزمايشگاهي تشخيصها

70

Diagnostic Criteria Inactive HBsAg Carrier State

Diagnostic Criteria Inactive HBsAg Carrier State

HBsAg+ > 6 months

HBeAg- , anti-HBe+

Serum HBV DNA < 105 copies/ml

Persistently normal ALT

HBsAg+ > 6 months

HBeAg- , anti-HBe+

Serum HBV DNA < 105 copies/ml

Persistently normal ALT

HBV - DiagnosisHBV - Diagnosis

Inactive carrier state

Inactive Carrier State

• HBsAg+ > 6 months

• HBeAg –ve

• Normal ALT

• HBV DNA < 105 copies/ml

• Positive HBV DNA PCR in 70-80%

• Liver Bx HAI < 4 (optional)

• Precore mutation in 70%

• Treatment is not recommended

Martinot-Peignoux M et al. J Hepatol 2002;36:543-6

Management Plan for Inactive Carriers

• HCV Ab, HDV Ab

• Quantitative HBV DNA

• Periodic ALT: every 6 -12 months

• Periodic AFP (endemic areas)

• Family screening for HBV

• Vaccination if HBsAg –ve

Genotyping of HBV ?

Outcome of Inactive Carriers

• Outcome is good

• On 8 years follow up (China):

• Cirrhosis: 0.5%

• HCC: 1.5%

Hsu YS et al. Hepatology 2002;35:1522-7

69

Diagnostic CriteriaChronic Hepatitis BDiagnostic CriteriaChronic Hepatitis B

HBsAg+ > 6 months

Serum HBV DNA > 105 copies/ml

Persistent or intermittent elevation in ALT

Liver biopsy HAI 4 (optional)

HBsAg+ > 6 months

Serum HBV DNA > 105 copies/ml

Persistent or intermittent elevation in ALT

Liver biopsy HAI 4 (optional)

HBV - DiagnosisHBV - Diagnosis

Chronic hepatitis B

72

Chronic infection - HBsAg+ >6 months

Replicative infection - HBV DNA > 105 copies/ml

HBeAg positive or negative

Active liver disease - ALT >2 x normal

Chronic hepatitis cirrhosis

Indications for TreatmentIndications for Treatment

HBVHBV

Indications of HBV treatment

هپاتیت درمانی Bداروهایمزمن

ایمونومدوالتورها-1و معمولی Pegylatedانترفرون

نوکلئوزیدی- 2 های آنالوگالمیودینآدفوویر

تنوفوویرانتکاویر

Recommendations in HBeAg +veCHB

• IFN 10 MU TIW for 4 monthsOr

• Lamivudine 100 mg/d for 1 year or more (3- 6 months after seroconversion)

Or• Adefovir 10 mg/d for 1 year or more• Treatment end points:

•Normalization of ALT•Undetectable HBV DNA (non-PCR)•HBeAg loss

• Sustained response (12 months after D/C of therapy) is important

• Positive PCR after treatment is not important

86

Adverse Effects of IFNAdverse Effects of IFN

Flu-like illness

Fatigue

Emotional lability / depression

Bone marrow suppression

Thyroid dysfunction

Exacerbation of autoimmune disease

Flu-like illness

Fatigue

Emotional lability / depression

Bone marrow suppression

Thyroid dysfunction

Exacerbation of autoimmune disease

HBV - TherapyHBV - Therapy

Adverse effects of interferon

68

Causes of Acute Hepatitis in HBsAg+ Persons

Causes of Acute Hepatitis in HBsAg+ Persons

HBsAg-positiveAcute HepatitisHBsAg-positiveAcute Hepatitis

Non-viral liver injury

Non-viral liver injury

Acute HBV infection

Acute HBV infection

HBV reactivationHBV reactivation

HBeAg anti-HBeseroconversion

HBeAg anti-HBeseroconversion

Superinfection

HAV

HDV

HCV

HEV

? Other

Superinfection

HAV

HDV

HCV

HEV

? Other

HBV - Diagnosis HBV - Diagnosis

Acute hepatitis in persons who are HBsAg positive

YMDD Mutants

• Incidence of YMDD mutants:

•One year treatment: 20%

•Two years treatment: 40% to 60%

END

Genotype

• Genotype C is associated with more rapidly progressive liver disease

• HBeAg-negative (precore mutant) HBV is most common in genotypes C, and D

• Genotypes A and B appear to have greater rates of antiviral response to IFN than D and C.

• Testing for HBV genotype is not yet performed in clinical practice

هپاتیت C تشخیص

هپاتیت - یا Cبیماری حاد تحت و مزمن موارد اکثر در سیرآزمایشسرولوژی ودر دارد عالمت مثبت HVC Abبی

اگر% 20 لذا شده ویروسحذف منفی HCV PCRمواردپدیده برای بعد ماه سه اگر Windowشد شود می تکرار

با بیماری بود منفی .HCVباز شود می ردبیماری و است بیماری در ها آمیناز ترانس تموج مهم نکته

برود HCVکبدی سیروز طرف به تواند می نرمال آنزیم باکمک بیوپسی جای به فیبراسکن با کبد االستیسیته بررسی

است کننده

Symptoms, or Lack of, in Chronic HCV Infection

Symptomatic37%

Cirrhosis7%

56%Asymptomatic

0

20

40

60

80

100

Fatigue

Pat

ien

ts(%

)

80

ALT Elevations Are Not Indicative of Chronic HCV Infection

Inglesby TV, et al. Hepatology. 1999;29:590-596.

42 43

15

0

20

40

60

80

100

PersistentlyNormal ALT

IntermittentlyElevated ALT

Persistently Elevated ALT

Pat

ien

ts*

Wit

h H

CV

infe

ctio

n)%

(

Diagnostic Tests for HCV Infection

Diagnostic Test TypeSpecifications Serologic VirologicMode of detection Antibodies VirusSensitivity > 95% > 98%Specificity Variable > 98%Detection postexposure 2-6 mos 2-6 wks

Use Screening ConfirmationCDC Morbidity Mortality Weekly Report. 1998;16(RR-19):1-33. NIH

Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.

Accessed April 10, 2007.

Clinical Significance of HCV Genotypes

Choo QL, et al. Science. 1989;244:359-62. NIH Consensus Development Conference Statement. Bethesda, Md: National Institutes of Health;

June 10-12, 2002. Hadziyannis SJ. Ann Intern Med. 2004;140:346-355.

•Great genetic diversity: 2 genotypes (1 through 6)–Multiple subtypes: a, b, c, etc

•Genotype is best pretreatment predictor of response–Genotype 1: least responsive to therapy

•Determines dose and duration of therapy–Genotype 1: 48 weeks of peg-IFN alfa + RBV 1000-1200

mg–Genotype 2/3: 24 weeks of peg-IFN alfa + RBV 800 mg•All patients should have genotype determined prior to

initiating therapy

Prevalence of HCV Dependant on Risk Factors

•Hemophilia74-90%•IVDA72-89%•Prison40%

•HIV30-40%•Blood transfusion prior to 90 5-9%

•Infants to HCV+ Mothers5%•Sexual Partner0.5-3%

•General Population1.8%

Adapted from MMWR.1998;47:5.