CNG TY TNHH TRUNG TM Y KHOA PHC AN (HEPA)CNG HA X HI CH NGHA VIT NAMc lp T do Hnh phc

S: /TTr-HEPA-QLCL

TP.HCM, ngy 30 thng 07 nm 2015

T TRNHV/v Thng tin ng Tp san Y Dc ca phng QLCL

Knh gi: TNG GIM C Cn c ch o ca Tng Gim c v vic bin son thng tin ng Tp san Y Dc.Phng QLCL knh trnh Tng Gim c v thng tin ng Tp san Y Dc ca Cng ty nh sau:

1. Tiu : XT NGHIM DNG TRONG CHM SC V IU TR BNH NHN VIM GAN SIU VI B MN TNH THEO KHUYN CO NM 2015 CA T CHC Y T TH GII (WHO)2. Ngun tham kho: World Health Organization. "Guideline for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection, March, 2015.3. Ni dung:

1. Cc giai on ca bnh vim gan siu vi B mn tnhBng 1. Cc giai on ca bnh vim gan siu vi B mn tnh

Giai onTnh trng HBeAg huyt thanhM hnh bnh

1. Giai on dung np min dch (Immune tolerant)HBeAg dng tnhGiai on ny thng thy tr em hoc thanh nin c HBeAg dng tnh, c bit l nhng ngi b nhim virus vim gan B khi sinhMc sao chp HBV cao (mc HBV DNA > 200.000 lU/mL)Gi tr ALT mc bnh thng lu diBnh m mc ti thiu

2. Giai on hot ng min dch (Immune active)HBeAg dng tnh, c th c anti-HBeGi tr ALT bt thng hoc bt thng gin onMc sao chp HBV cao hoc dao ng ln xung (mc HBV DNA > 2.000 IU/mL)C hot ng vim hoi t (necroinflammatory) mC th c chuyn ha huyt thanh HBeAg thnh anti-HBe vi qu trnh bnh thng ha ALT chuyn sang giai on kim sot min dch

3. Giai on vim gan mn bt hot hay Giai on kim sot min dch (Immune control)HBeAg m tnh, anti-HBe dng tnhGi tr ALT mc bnh thng lu diMc HBV DNA thp hoc di ngng pht hin (mc HBV DNA < 2000 IU/mL)Nguy c x gan (cirrhosis) v ung th biu b gan (HCC) gimC th xut hin bnh HBeAg-m tnh

4. Giai on thot khi min dch (Immune escape)HBeAg m tnh, c hoc khng c anti-HBe dng tnhHBeAg m tnh v anti-HBe dng tnhGi tr ALT bt thng (bt thng ko di hoc gin on)Mc sao chp HBV t trung bnh n cao (mc HBV DNA > 20.000 IU/mL)Nguy c bnh tin trin ngi gi (x ha/x gan) (fibrosis/cirrhosis)

5. Giai on ti hot ha hoc Giai on cp bnh vim gan mn tnh (acute-on-chronic hepatitisHBeAg dng tnh hoc m tnhC th xy ra tc thi hoc rt nhanh do suy gim min dch khi bnh nhn c ha tr hoc dng liu php lm suy gim min dch, nhim HIV, cy ghp, bnh tin trin khng thuc khng virus hoc ngng s dng liu php khng virusGi tr ALT bt thngMc sao chp HBV t trung bnh n caoHi chuyn huyt thanh v tnh trng HBeAg dng tnh nu HBeAg m tnhBnh c nguy c mt b (decompensation) vi s xut hin ca x gan

Ghi ch:ALT: alanine aminotransferaseAnti-HBe: antibody to hepatitis e antigenHBeAg: hepatitis B e antigenHCC: hepatocellular carcinoma2. Cc xt nghim dng chn on bnh vim gan siu vi B mn tnhNhng ngi c HBsAg dng tnh cn phi c nh gi nh k c chm sc v iu tr khi cn thit. nh gi gm: cc du ch huyt thanh b sung ca HBV (HBeAg), mc aminotransferase xc nh mc vim gan, nh lng mc HBV DNA, v cc xt nghim x ha gan (liver fibrosis) khng xm ln nh ch s t l gia aspartate aminotransferase v tiu cu (APRI), n hi nht thi (FibroScan) hoc FibroTest.2.1. Cc du ch (marker) huyt thanh HBVNgi tng nhim HBV c xc nh bng cc khng th anti-HBs v anti-HBc. Kh nng min dch vi HBV sau khi tim chng c xc nh bng khng th anti-HBs (ch c khng th anti-HBs). Bnh nhn vim gan B mn tnh (CHB) c xc nh bng HBsAg n nh t nht trong 6 thng. Gn y, xt nghim HBsAg nh lng c s dng phn bit ngi mang HBsAg bt hot vi nhng ngi ang mc bnh.HBeAg: Cn phi xc nh xem mt ngi ang nhim virus vim gan B c HBeAg dng tnh hoc HBeAg m tnh, do c hai trng hp u cn c theo di lu di, do tnh trng bnh c th thay i theo thi gian. bnh nhn vim ban B mn tnh (CHB), kt qu HBsAg dng tnh cho bit HBV ang sao chp v c kh nng ly nhim cao. S ci thin tc thi c th din ra sau chuyn ha huyt thanh HBeAg dng tnh (anti-HBe), vi biu hin HBV gim sao chp, mc ALT tr li bnh thng. y l mt tin lng tt v khng cn iu tr. HBeAg c th c dng theo di p ng iu tr, do chuyn ha huyt thanh HBeAg (anti-HBe) nhng ngi HBeAg dng tnh vi kt qu ti lng HBV DNA di ngng pht hin bn vng c th c xem l im quyt nh dng iu tr. Tuy nhin, trng hp ny him khi xy ra, ngay c i vi liu php iu tr NA. Mt vi ngi vi kt qu HBeAg m tnh c sao chp HBV nhng dng tnh vi anti-HBe m khng sn sinh HBeAg do cc bin th HBV hoc t bin pre-core.2.2. nh gi virus HBVNng HBV DNA trong huyt thanh c nh lng bng phng php real-time PCR. Gi tr ny c tng quan vi din tin bnh, c dng phn bit tnh trng bnh ang din tin c HBeAg m tnh vi tnh trng nhim mn tnh khng hot ng, v quyt nh iu tr v theo di tip tc. Xt nghim c khuyn khch thc hin lin tc trong vi thng hoc lu hn. Tuy nhin, hin ti vn thiu s nht tr v mc nng HBV DNA xc nh tnh trng bnh khng hot ng, hoc ngng bt u iu tr. Nng HBV DNA cn c dng theo di p ng vi liu php iu tr khng virus, v kt qu gia tng cho bit s xut hin ca mt chng khng. Hin nay c tiu chun ca WHO biu din nng ca HBV DNA. Mc HBV DNA cn phi c th hin theo gi tr IU/mL m bo tnh c th so snh, cc gi tr c th hin di dng copies/mL c th c chuyn i thnh IU/mL bng cch chia cho 5, l gi tr gn ng m hu ht cc b kit xt nghim ph bin ang s dng (v d, 10.000 copies/mL = 2000 IU/mL; 100.000 copies/mL = 20.000 IU/mL).2.3. nh gi mc tn thng ganMt nh gi y bao gm cc nh gi lm sng v c im x gan v tnh trng mt b, v cc xt nghim bilirubin, albumin, ALT, AST, ALP, v thi gian prothrombin, cng nh tng phn tch t bo mu, bao gm gi tr tiu cu. Cc chn on khc bao gm siu m v xt nghim AFP theo di nh k ung th biu b gan (HCC), v k thut ni soi pht hin chng gin tnh mch nhng ngi b x gan.Cc enzyme gan: Aminotransferase c th dao ng theo thi gian, ch xt nghim ALT v AST khng bit c giai on bnh. Thng thng, nng ALT cao hn nng AST, nhng khi bnh din tin n x gan, t l AST/ALT c th o ngc. Cc xt nghim chng nng tng hp ca gan v/hoc cao huyt p cng (portal hypertension) bao gm albumin, bilirubin huyt thanh, s tiu cu, thi gian prothrombin. Din tin gim nng albumin, tng nng bilirubin huyt thanh v thi gian prothrombin ko di l biu hin ca din tin x gan mt b (decompensated cirrhosis).Sinh thit gan: Sinh thit gan c dng xc nh mc vim hoi t (necroinflammation) v x ha h tr quyt nh iu tr. C nhiu phng php c thit lp nh gi m v o lng hot ng vim hoi t (necroinflammation) theo tng giai on (x ha). Tuy nhin, phng php ny c nhiu gii hn, bao gm nhm mu, kt qu c yu t ch quan, gi cao, v nguy c gy chy mu v trn kh ph mc (pneumothorax), gy kh chu cho bnh nhn, c im bnh hc ca bnh nhn vim gan B mn tnh th hin qua sinh thit gan ph thuc vo giai on bnh, p ng min dch ca ngi bnh v mc sao chp ca virus.Cc xt nghim khng xm ln (NIT): Cc phng php khng xm ln nh gi cc giai on bnh gan c dng thay th cho phng php sinh thit gan v c thm nh trn ngi trng thnh mc bnh vim gan B mn tnh. Cc du ch (marker) trong mu i vi x ha (fibrosis), bao gm APRI v FIB-4, cng nh cc du ch thng mi nh FibroTest, hoc phng php o n hi nht thi (FibroScan) c thc hin loi tr x gan tin trin (advanced fibrosis).2.4. Sng lcHu ht nhng ti liu hng dn quc t u khuyn co sng lc HBsAg i vi nhng nhm ngi c nguy c cao, v nhng ngi c nguy c v cha min dch cn c chng nga virus vim gan B. Nhng ngi ny gm: nhng ngi thn hoc ngi c quan h tnh dc vi bnh nhn vim gan B mn tnh, nhng ngi nhim HIV, nhng ngi dng thuc tim, nhng ngi nam quan h tnh dc ng gii, nhng ngi hnh ngh mi dm, v mt s nhm ngi c nguy c khc. Nhng ngi hin mu hoc hin tng cn c sng lc HBsAg v cc bnh ly qua ng mu theo khuyn co ca WHO phng nga nhim HBV. 3. Cc k thut chn on khng xm ln dng chn on cc giai on bnh gan theo khuyn co ca WHOXt nghim APRI (aspartate aminotransferase (AST)-to-platelet ratio index) l mt xt nghim khng xm ln (NIT) c khuyn dng nh gi x gan (im APRI > 2 ngi trng thnh) cho nhng trng hp c ngun kinh ph gii hn. K thut o n hi nht thi (v d FibroScan) hoc FibroTest c khuyn dng cho nhng trng hp khng b gii hn v kinh ph v nhng ni m nhng k thut ny sn c (Khuyn co c iu kin, chng c c cht lng khng cao).Bng 2. Mt s xt nghim khng xm ln dng nh gi gia on x ha gan

Xt nghimThnh phnnh gi giai on x haYu cuChi ph

APRIAST, s tiu cu>= F2, F4 (x gan)K thut xt nghim sinh ha v huyt hc c bn+

FIB-4 tui, AST, ALT, s tiu cu>= F3K thut xt nghim sinh ha v huyt hc c bn+

FibroTestGamma glutamyl transpeptidase (gGT), haptoglobin, bilirubin, A1 apolipoprotein, alpha2-macroglobulin>= F2, >= F3, F4 (x gan)Xt nghim chuyn bit. ++

FibroScan n hi nht thi>= F2, >= F3, F4 (x gan)Thit b chuyn dng.+++

Cng thc tnh APRIAPRI = (AST/ULN) x 100) / S tiu cuTrong :AST tnh bng n v IU/LULN l gi tr ngng trn ca khong gi tr bnh thng ca xt nghim AST c s dng trong phng xt nghimS tiu cu tnh bng n v 109/LCng thc tnh FIB-4FIB-4 = ( tui x AST) / (S tiu cu x (ALT)1/2)Trong : tui tnh bng n v nmAST tnh bng n v IU/LS tiu cu tnh bng n v 109/LALT tnh bng n v IU/L

Bng 3. Bng tm tt nhy, c hiu, v gi tr d on m tnh v dng tnh ca xt nghim APRI, FibroTest v n hi nht thi (FibroScan) trong pht hin x gan (F4) v x ha r rt (>= F2)

APRI (ngng thp) (low cut-off)APRI (ngng cao) (high cut-off)FibroTest n hi nht thi (FibroScan)

X gan (METAVIR F4) nhy (%) (95% CI)65 (55-73)35 (22-49)88 (78-94)86 (81-90)

c hin (%) (95% CI)75 (70-80)89 (8194) 73 (6679) 87 (8390)

Gi tr d on dng tnh (%) (95% CI)22 (1828)

26 (1934) 27 (2232) 42 (35-49)

Gi tr d on m tnh (%) (95% CI)95 (9397) 92 (9194) 98 (9799) 98 (97-99)

X ha r rt (METAVIR >= F2) nhy (%) (95% CI)78 (7184) 36 (2845) 68 (5976) 76 (7180)

c hin (%) (95% CI)60 (5069) 92 (9095) 84 (7590) 82 (7587)

Gi tr d on dng tnh (%) (95% CI)57 (5261) 75 (6881) 74 (6978) 74 (6978)

Gi tr d on m tnh (%) (95% CI)80 (7684)68 (6572)80 (7683)84 (8087)

4. Cc xt nghim l cn c quyt nh iu tr hoc khng iu tr i vi bnh nhn vim gan siu vi B mn tnh theo khuyn co ca WHO4.1. Nhng bnh nhn cn iu tru tin iu tr cho tt c ngi trng thnh, thanh thiu nin v tr em mc bnh vim gan siu vi B mn tnh c chng c lm sng ca x gan cn b hoc mt b (hoc da trn im s APRI > 2 ngi trng thnh), bt k gi tr ALT, tnh trng HBeAg hoc mc HBV DNA. (Khuyn co mnh m, chng c c cht lng tng i cao)Khuyn co iu tr cho nhng ngi trng thnh mc bnh vim gan siu vi B mn tnh c chng c lm sng ca x gan (hoc da trn im s APRI 20.000 IU/mL), bt k tnh trng HbeAg. (Khuyn co mnh m, chng c c cht lng tng i cao)4.2. Nhng bnh nhn khng cn iu tr nhng phi theo diLiu php iu tr bng thuc khng virus khng c khuyn co v c th tr hon nhng ngi khng c chng c x gan (hoc da trn im s APRI 20.000 IU/mL nhng c mc ALT bnh thng n nh trong thi gian di;Nhng ngi c kt qu HBeAg m tnh khng b x gan c tui t 30 tr xung, c mc HBV DNA dao ng trong khong 2.000 v 20.000 IU/mL, hoc c mc ALT bt thng gin on.5. Cc xt nghim l cn c quyt nh dng iu tr i vi bnh nhn vim gan siu vi B mn tnh theo khuyn co ca WHO5.1. Liu php iu tr NA sut iTt c nhng ngi b x gan da trn chng c lm sng (hoc im s APRI > 2 ngi trng thnh) cn c iu tr sut i bng nucleoside analogues (NA), v khng c dng iu tr bng liu php khng virus do nguy c ti hot ha c th lm tn thng gan nghim trng. (Khuyn co mnh m, chng c c cht lng khng cao)5.2. Dng iu trDng iu tr bng NA c th c xem xt theo tng trng hp c bit nh sau: Nhng ngi khng c chng c lm sng x gan (hoc da trn im s APRI