Điều trịdaas và nguy cơphát triển hcc trên bn nhi m...

T VN, CHN ON,

IU TR BNH VGVR C

TRONG THC HNH LM

SNG THEO HNG DN

NM 2016 - B Y T

iu tr DAAs v nguy

c pht trin HCC

trn BN nhim HCV

2

HNG DNCHN ON V IU TR BNH VIM GAN VI RT C(Ban hnh km theo Quyt nh s 5012/Q-BYT ngy 20

thng 9 nm 2016 ca B trng B Y t)

I. I CNG

II. CHN ON VIM GAN VI RT C

1. Triu chng

2. Chn on xc nh

3. Xc nh cc bnh l i km

III. IU TR VIM GAN VI RT C

1. iu tr vim gan vi rt C cp

2. iu tr vim gan vi rt C mn tnh

3. Theo di iu tr

6 Bng; 3 Ph lc

T VN IU TR VGVR C

Khi chun b iu tr khng HCV

3

1

1. MC CH T VN

BN, TN quyt nh, hp tc v tun th iu tr.4

Cung cp thng in, trao i, tho lun trc tip vi

BN v thn nhn v:

Bnh Vim

gan vi rt C

(VGVR C)

Mc tiu, yu cu (chn on,

iu tr, theo di); hiu qu, li

ch v chi ph iu tr.

2. NI DUNG T VN

ng ly nhim HCV.

Din tin t nhin, cc bin chng ca bnh.

Mc tiu iu tr: loi tr HCV (khi bnh).

Ch nh v li ch ca iu tr.

XN cn thc hin: trc, trong v sau iu tr.

Cc phc iu tr: hiu qu, thi gian v chi ph.

5

Tc dng khng mong mun ca thuc, tng tc thuc,

Kh nng sinh qui thai ca thuc trnh thai trong v 6 thng

sau iu tr i vi BN v bn tnh.

Kh nng HCC trong hoc sau iu tr trn BN gan b x ha

nhiu (F3).

Li ch ca tun th iu tr.

V tc hi v nn trnh cc thc ung c cn.6

2. NI DUNG T VN

CHN ON VGVR C

7

2Chn on xc nh

1. VIM GAN VI RT C CP

8

Chn on nhim HCV cp khi:

(1) o Anti-HCV t m sang dng

hay

(2) Anti-HCV m v HCV RNA dng.

Nhim HCV < 6 thng Lm sng: c th mt, vng mt, vng da,...

AST, ALT thng tng; HCV RNA: dng sau 2 tun; Anti-HCV dng sau 8 - 12 tun phi

nhim.

1 2 3

0 10 20 30 40 50 60 70 80 90 180

HCV RNA

HCV Ag

Anti HCV

Anti HCV (+) HCV RNA (+)

Ngy

Giai on ca s

Nhim HCV cp

KH CHN ON TRN LM SNG

10

2. VIM GAN VI RT C MN

C hoc khng

c biu hin

lm sng.

Thi gian nhim

HCV > 6 thng.

Khng hoc c

x ho gan, x

gan.

Anti-HCV dng

v HCV RNA

dng hoc HCV

core-Ag dng.

4

2

1

3

11

3. VIM GAN VI RT C TR EM

Xt nghim HCV RNA

lc 6 thng v 12

thng;

+: 2 ln HCV RNA

dng.

+: nh ngi ln

Anti-HCV dng

v HCV RNA dng

TR < 18 THNG TUI TR > 18 THNG TUI

CHN ON VGVR C

12

2

Xc nh cc bnh l i km

13

CH THC HIN KHI THT S CN THIT

XC NH CC BNH L I KM

BN cn c xt nghim kim tra

ng nhim VRVG: B, D, E, A;

Vim gan t min;

Vim gan do ru;

Vim gan nhim m khng do ru;

Nhim HIV, tiu ng, bnh tuyn gip

IU TR VGVR C

14

3

15

1. IU TR VIM GAN VI RT C CP

Nn theo di HCV RNA t nht 12 tun sau chn on; nu HCVRNA dng sau 12 tun iu tr DAAs nh vi VGVR C mn

iu tr h tr: ngh ngi v iu tr triu chng.

iu tr c hiu:

Khng khuyn co.

Xem xt khi: c biu hin bnh nng hn, e da tnh

mng.

16

2.1. Mc tiu iu tr

Loi tr HCV: t SVR 12 (ngng < 15

IU/ml); SVR 24 khi iu tr c Peg-interferon).

Phng nga cc bin chng v gan v cc

bnh ngoi gan lin quan n HCV

D phng ly nhim HCV trong cng ng.

2. IU TR VIM GAN VI RT C MN

17

2.2. Thuc iu tr

18

Peg IFN

Ribavirin

DAAs

19


Ngi bnh cn c khm lm sng ton din v lm cc xt nghim

i vi ph n trong tui sinh sn hoc nghi ng c thai cn xt nghim th thai nh tnh.

T vn cho ngi bnh

2.3. Chun b iu tr

20


Thi gian PegIFN + RBV + SOF DAA+RBV DAA

CTM,

chc nng

gan, thn

Chc nng

tuyn gip

Siu m

bng,

Xquang

phi, in

tm , AFP

nh gi x

ha gan

( phng

php khng

xm nhp)

HCV

RNA

HBsAg, HIV,

kiu gen

HCV

CTM, chc

nng gan,

thn

Siu m

bng, AFP

nh gi x

ha gan

( phng

php khng

xm nhp)

HCV

RNA

*

HIV,

HBsAg,

kiu gen

HCV

CTM,

chc

nng

gan, thn

Siu m

bng,

AFP

nh gi x

ha gan

( phng

php khng

xm nhp)

HCV

RNA

*

HIV,

HBsAg,

kiu gen

HCV

Trc iu tr X X X X X X X X X X X X X X X X

Ph lc 2. Cc xt nghim cn theo di trc, trong v sau iu tr vim gan vi rt C mn(Ban hnh km theo Quyt nh s 5012/Q-BYT ngy 20 thng 9 nm 2016 ca B trng B Y t)

21


Khng xc nhc kiu gen ths dng phc iu tr c chokiu gen 6.

HCV RNA dng v anti-HCV dng

2.4. Ch nh iu tr:

Khi c cc iu kin:

Da vo kiu gen,cc CC, tngtc thuc v bnhi km lachn cc phc .

La chn ban u:phc thucDAAs; la chnthay th: phc c Peg-IFN

c

22

Kiu

gen

SOF/LDV

SOF +

DCV

SOF

+RBV GZR/EBR SOF/VEL

SMV +

SOF

PTV/OBV/

r + DSV

PTV/OBV

/r

PegIFN +

RBV+SOF

1a 12 tun 12 tun Khng 12 tun 12 tun 12 tun 12 tun

(+RBV) Khng 12 tun

1b 12 tun 12 tun Khng 12 tun 12 tun 12 tun 12 tun Khng 12 tun

2 Khng 12 tun 12 tun Khng 12 tun Khng Khng Khng 12 tun

3 Khng 12 tun 24 tun Khng 12 tun Khng Khng Khng 12 tun

4 12 tun 12 tun Khng 12 tun 12 tun 12 tun Khng 12 tun

(+RBV) 12 tun

5,6 12 tun 12 tun Khng Khng 12 tun Khng Khng Khng 12 tun

PHC IU TR VGVR C MN / KHNG X GAN

THI GIAN IU TR 12 TUN,

CH KIU GEN 2, 3: MI DNG SOF+RBV; KHNG DNG LDV

NGOI TR

23

PHC IU TR VGVR C MN / X GAN CN B (CHILD PUGH A)

Kiu

genSOF/LDV SOF + DCV

SOF

+RBVGZR/EBR SOF/VEL SMV + SOF

PTV/OBV/r

+ DSV

PTV/

OBV/r

PegIFN +

RBV+SOF

1a

24 tun hoc

12 tun ( +

RBV)

24 tun hoc

12 tun

(+RBV)

Khng 12 tun 12 tun

24 tun hoc

12 tun

(+RBV)

24 tun

(+RBV)Khng 12 tun

1b

24 tun hoc

12 tun ( +

RBV)

24 tun hoc

12 tun

(+RBV)

Khng 12 tun 12 tun

24 tun hoc

12 tun

(+RBV)

12 tun

(+RBV)Khng 12 tun

2 Khng 12 tun16 20

tunKhng 12 tun Khng Khng Khng 12 tun

3 Khng24 tun +

RBVKhng Khng 12 tun Khng Khng Khng 12 tun

4

24 tun hoc

12 tun

(+RBV)

24 tun hoc

12 tun

(+RBV)

Khng 12 tun 12 tun

24 tun hoc

12 tun

(+RBV)

Khng24 tun

(+RBV)12 tun

5,6

24 tun hoc

12 tun

(+RBV)

24 tun hoc

12 tun

(+RBV)

Khng Khng 12 tun Khng Khng Khng 12 tun

24

PHC IU TR VGVR C MN / X GAN MT B (CHILD PUGH B, C)

KIU GEN SOF+RBV SOF/LDV SOF/DCV SOF/VEL

1,4,5,6

24 tun

Hoc 12 tun

(+RBV)

24 tun

hoc 12 tun

(+RBV) 24 tun

hoc 12 tun

(+RBV)2 16-20 tun Khng

24 tun hoc 12

tun (+RBV)

3 Khng24 tun hoc12

tun (+RBV)

Lu :

RBV khi u vi liu 600mg, tng liu dn theo cn nng nu dung np tt.

Cn c theo di ti c s iu tr chuyn khoa/a khoa tuyn tnh hoc

tuyn trung ng.

25


2.4. Ch nh iu tr:

Cc phc s dng DAAs th h mi, cha

cp trong Hng dn, c th c xem xt, b

sung da theo cc Hng dn chuyn mn ca

WHO, APASL, EASL, AASLD v theo cc quy

nh lin quan n s dng thuc ti Vit Nam.

26


2.5. Chng ch nh:

Cha c khuyn co cho ngi di 18 tui; Ph n c thai

Nh Hng dn 2013

Chng ch nh tuyt i khi+ Thiu mu nng (hemoglobin < 8,0 g/dL).+ Ph n: c thai; khng mun trnh thai; ang cho con b.+ ang mc cc bnh nng khc gm c bnh nhim trng nng.+ Suy tim khng kim sot c; Bnh phi tc nghn mn tnh.

i vi phc c cc thuc DAAs

i vi phc c Peg interferon

i vi phc c Ribavirin

27

2.6. iu tr mt s trng hp c bit

Nh Hng

dn 2013

TR EM NG NHIM HIV

iu tr tng t nh VGVR C khng nhim HIV, u tin

dng DAAs

NG NHIM VI HBV

iu tr ging ngi bnh vim gan virt C n thun.

Nu HBV ang tng sinh (HBV DNA 2000UI/ml / HBeAg m hoc 20.000UI/ml / HBeAg dng phihp thm thuc khng HBV.

Ch tng tc: LDV v TDF c thtng c tnh thn.


28

2.6. iu tr mt s trng hp c bit

nh gi mc suy thn da vo thanh thi Creatinin (CrCl), la chn thuc, liu

lng thch hp

NGI BNH C BNH THN MN TNH

NGI BNH NG NHIM LAO/HCV

iu tr lao tin trin trc, khi n nh th iu tr vim gan vi rt C.

iu tr ging ngi bnh vim gan vi rt C. Lu tng tc gia cc thuc DAAs v

rifampicin


29

3. THEO DI IU TR

3.1. Theo di tc dng khng mong mun

Cc thuc DAAs c mt s tc dng ph nh,

thng t khi.

Theo di cht ch ngi s dng phc c

PegIFN, ribavirin, iu tr cc bnh km theo.

i vi ngi ang s dng cc thuc khc

cn lu tng tc vi thuc iu tr VGVR C.

30

3. THEO DI IU TR

3.2. Theo di p ng iu tr vim gan C mn tnhiu tr khi

t SVR 12. Cn theo di sau ngng iu tr 24 tun bng XN nh lng HCV RNA bo m khng b ti pht.

iu tr khi

Theo di ngi bnh sau khi iu tr khi

Bin chng HCC (k c ngicha iu tr), c bit ngi c x ha gan t F3tr ln bng SA bng v AFPmi 3-6 thng. C th sdng cc XN: AFP-L3, PIVKA-II pht hin sm HCC.

Ngi c nguy c tinhim HCV hoc tngmen gan: cn kim tranh lng HCV RNA pht hin ti pht hocnhim HCV mi.

cc

31

3. THEO DI IU TR

3.2. Theo di p ng iu tr vim gan C mn tnh

iu tr li i vi ngi bnh tht bi iu tr

Tht bi iu tr

i vi cc trng hp tht bi iu tr

Khng t SVR12

Nn hi chn xin kin chuyn gia chn la phc thch hp cho tngc th

c

32

3. THEO DI IU TR

3.2. Theo di p ng iu tr vim gan C mn tnh

Ngng iu tr

Do tc dng khng mong mun

Do khng png v virus

Nng, e da tnh mng (c bit i vi phc c Peg IFN).

HCV RNA tun 4 iu tr trn ngng nh lng HCV RNA ti tun 8;

Nu tng >10 ln (> 1 log10 IU/ml) ngng iu tr.

Cn hi chn xem xt i phc iu tr.

33


Ph lc 2. Cc xt nghim cn theo di trc, trong v sau iu tr vim gan vi rt C mn

(Ban hnh km theo Quyt nh s 5012/Q-BYT ngy 20 thng 9 nm 2016 ca B trng B Y t)

Thi gian PegIFN + RBV + SOF DAA+RBV DAA

CTM,

chc nng

gan, thn

Chc

nng

tuyn gip

Siu m

bng,

Xquang

phi, in

tm ,

AFP

nh gi

x ha gan

( phng

php khng

xm nhp)

HCV

RNA

HBsAg,

HIV, kiu

gen HCV

CTM, chc

nng gan,

thn

Siu m

bng, AFP

nh gi

x ha gan

( phng

php

khng xm

nhp)

HCV

RNA

*

HIV,

HBsAg,

kiu gen

HCV

CTM,

chc

nng

gan, thn

Siu m

bng,

AFP

nh gi

x ha gan

( phng

php khng

xm nhp)

HCV

RNA

*

HIV, HBsAg,

kiu gen

HCV

Tun 4 T X X X X X X X

Tun 8 T X X* X X* X*

Tun 12 T X X X X X X X

12 tun sau

iu tr X X X X X X X X X X X X

24 tun sau

iu trX X X X XX X

A 10-fold increase in alanine

aminotransferase (ALT) activity at

week 4 should prompt discontinuation

of therapy. Any increase in ALT of

less than 10-fold at week 4 and

accompanied by any weakness,

nausea, vomiting, jaundice, or

significantly increased bilirubin,

alkaline phosphatase, or international

normalized ratio, should also prompt

discontinuation of therapy.34

HCV Guidance: Recommendations for Testing,

Managing, and Treating Hepatitis C. July 2016

Asymptomatic increases in

ALT of less than 10-fold

elevated at week 4 should be

closely monitored and

repeated at week 6 and week

8. If levels remain persistently

elevated, consideration should

be given to discontinuation of

therapy

35

PHC IU TR LI CHO NGI THT BI IU TR

Phc iu

tr tht bi

Phc iu tr li v thi gian iu tr

Tn phc thay th Khng x gan X gan cn b X gan mt b

Kiu gen 1

PegIFN +

RBV

SOF/LDV 12 tun 24 tun hoc 12 tun (+RBV)

SOF/VEL 12 tun 12 tun 12 tun (+RBV)

SOF+DCV 12 tun 24 tun ( RBV)

GZR/EBR 12 tun 12 tun Khng s dng

SMV+SOF 12 tun 24 tun Khng s dng

OBV/PTV/r+DSV 12 tun- kiu gen 1b Khng s dng

OBV/PTV/r+DSV+RBV 12 tun- kiu gen 1a 12 tun- kiu gen 1b

24 tun- kiu gen 1a

Khng s dng

SOF + RBV +

PegIFN

SOF/LDV 12 tun (+RBV) 24 tun (+RBV)

SOF/VEL 12 tun 12 tun (+RBV)

PegIFN +

RBV vi

telaprevir

hoc

boceprevirho

c SMV

SOF+DCV 12 tun 24 tun (RBV)



GZR/EBR 12 tun (+RBV) 12 tun (+RBV) Khng s dng

SMV + SOF

SOF+DCV 12 tun +RBV; 24 tun +RBV nu x ha F3 hoc x gan

SOF/LDV 12 tun +RBV; 24 tun +RBV nu x ha F3 hoc x gan


36

Kiu gen 2

PegIFN +

RBV

SOF+DCV 12 tun 24 tun


SOF + RBV

SOF+DCV + RBV 24 tun

Peg-IFN+ RBV +SOF 12 tun 12 tun Khng s dng


Kiu gen 3

PegIFN +

RBV

SOF+DCV 12 tun 24 tun (RBV)


SOF/VEL 12 tun 12 tun (+ RBV)

SOF + RBV

SOF+DCV + RBV 24 tun 24 tun


SOF/VEL +RBV 12 tun

Kiu gen 4

PegIFN +

RBV


OBV/PTV/r++RBV 12 tun 12 tun


GZR/EBR 12 tun 12 tun Khng s dng

SOF +DCV 12tun 24 tun hoc 12 tun (+RBV)

SOF/VEL 12 tun 12 tun

Kiu gen 5 v 6

PegIFN +

RBV

SOF/LDV 12 tun +RBV

SOF+DCV 12 tun 24 tun hoc 12 tun (+RBV)


SOF/VEL 12 tun

Lu :

Cc trng hp

tht bi iu tr vi

cc phc cha

cp, vic la

chn phc iu

tr li phi c

kin hi chn vi

chuyn gia trong

tng trng hp c

th.

PHC IU TR LI CHO NGI THT BI IU TR

IU TR DAAs V NGUY

C PHT TRIN HCC TRN

NGI NHIM HCV37

4

38

1. T NHNG NGHIN CU TRN TH GII

HCC xut hin ngay sau khi

iu tr DAAs nghi ng iu

tr DAAs lm tng nguy c HCC.

39


Bo co t Barcelona: c mi

lin h gia s gia tng HCC vi

iu tr DAAs; t l ti pht HCC

bt ng cao ngay sau khi iu tr

DAAs: 27,6% (Reig, Mario,

2016).

40


41


NC on h 24 trung tm ti Veneto, (thng 01/2015 06/2016)

N=3.075 BN nhim HCV; a s kiu gen 1a/b (62.1%); x ha F3 hoc F4

(72,3%): Child-Pugh A 65,3% v B 7%.

BN c iu tr DAAs theo cc Hng dn quc t; thng dng nht l

SOF+LDVRBV t 12 n 24 tun (33,8%).

BN c theo di sau khi bt u iu tr DAAs.

42


KT QU:

Hiu qu iu tr ca

DAAs gim trn BN c

x ha cao.

43


T l BN b HCC:

Sau 300 ngy: 1,64%

Sau 18 thng: 2,5%

(t hn so vi khng iu tr:

2,8% v 3,9%).

KT QU: T l HCC tng theo mc XG

44


Phn tch n bin:

Khng t SVR c kh nng pht

trin HCC cao hn (8,38%) so

vi nhng ngi p ng vi

DAA (1,55%).

45


iu tr bng DAAs khng lm

tng nguy c pht trin ung th

biu m t bo gan (HCC) BN

nhim HCV; nn theo di cht ch

HCC khi iu tr DAAs cho bnh

nhn gan x ha nhiu.

46

2. N HNG DN - B Y T 2016

Theo di bin chng HCC (k c ngi bnh

cha iu tr), c bit ngi bnh c

x ha gan t F3 tr ln: bng siu m bng

v AFP mi 3-6 thng. C th xem xt s

dng cc xt nghim:AFP-L3, PIVKA-II

pht hin sm HCC.

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