CNG TY TNHH TRUNG TM

Y KHOA PHC AN (HEPA)

S:
/TTr-HEPA-QLCL

CNG HA X HI CH NGHA VIT NAM

c lp T do Hnh phc
TP.HCM, ngy 30 thng 07 nm 2015

T TRNH
V/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 tnh

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

Tnh trng HBeAg huyt M hnh bnh

thanh
1. Giai on dung HBeAg dng tnh
Giai on ny thng thy tr em
np min dch
hoc thanh nin c HBeAg dng tnh,
(Immune
c bit l nhng ngi b nhim virus
tolerant)
vim gan B khi sinh
Mc sao chp HBV cao (mc HBV
DNA > 200.000 lU/mL)
Gi tr ALT mc bnh thng lu di
Bnh m mc ti thiu
2. Giai on hot HBeAg dng tnh, c th Gi tr ALT bt thng hoc bt thng
ng min dch c anti-HBe
gin on
(Immune active)
Mc sao chp HBV cao hoc dao ng
ln xung (mc HBV DNA > 2.000
IU/mL)
C hot ng vim hoi t
(necroinflammatory) m
C th c chuyn ha huyt thanh
HBeAg thnh anti-HBe vi qu trnh

3. Giai on vim HBeAg m tnh, anti-HBe

gan mn bt hot dng tnh
hay Giai on
kim sot min
dch
(Immune
control)
4. Giai on thot HBeAg m tnh, c hoc
khi min dch khng c anti-HBe dng
(Immune escape) tnh

5. Giai on ti HBeAg dng tnh hoc

hot ha hoc m tnh
Giai on cp
bnh vim gan mn
tnh
(acute-onchronic hepatitis

bnh thng ha ALT chuyn sang

giai on kim sot min dch
Gi tr ALT mc bnh thng lu di
Mc 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) gim
C th xut hin bnh HBeAg-m tnh
HBeAg m tnh v anti-HBe dng tnh
Gi 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)
C 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 virus
Gi tr ALT bt thng
Mc sao chp HBV t trung bnh n
cao
Hi chuyn huyt thanh v tnh trng
HBeAg dng tnh nu HBeAg m tnh
Bnh
c
nguy c
mt
b
(decompensation) vi s xut hin ca
x gan

Ghi ch:
ALT: alanine aminotransferase
Anti-HBe: antibody to hepatitis e antigen
HBeAg: hepatitis B e antigen
HCC: hepatocellular carcinoma

2. Cc xt nghim dng chn on bnh vim gan siu vi B mn tnh

Nhng 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 HBV

Ngi 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 HBV
Nng 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 gan
Mt 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 lc
Hu 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 WHO

Xt 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 nghim
APRI

FIB-4

Thnh phn

nh gi giai
Yu cu
on x ha
AST, s tiu cu >= F2, F4 (x K thut xt +
gan)
nghim
sinh
ha v huyt
hc c bn
tui, AST, >= F3
K thut xt +
ALT, s tiu cu
nghim
sinh
ha v huyt

Chi ph

FibroTest

FibroScan

Gamma
glutamyl
transpeptidase
(gGT),
haptoglobin,
bilirubin,
A1
apolipoprotein,
alpha2macroglobulin
n hi nht
thi

hc c bn
>= F2, >= F3, Xt
nghim ++
F4 (x gan)
chuyn bit.

>= F2, >= F3, Thit b chuyn +++

F4 (x gan)
dng.

Cng thc tnh APRI

APRI = (AST/ULN) x 100) / S tiu cu
Trong :
AST tnh bng n v IU/L
ULN l gi tr ngng trn ca khong gi tr bnh thng ca xt nghim AST c s
dng trong phng xt nghim
S tiu cu tnh bng n v 109/L
Cng thc tnh FIB-4
FIB-4 = ( tui x AST) / (S tiu cu x (ALT)1/2)
Trong :
tui tnh bng n v nm
AST tnh bng n v IU/L
S tiu cu tnh bng n v 109/L
ALT 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)
X
gan nhy (%) 65 (55-73)
(METAVIR
(95% CI)
F4)
c hin 75 (70-80)
(%)
(95%
CI)
Gi tr d 22 (1828)
on dng
tnh
(%)
(95% CI)
Gi tr d 95 (9397)
on
m

APRI
(ngng
cao) (high
cut-off)
35 (22-49)

FibroTest

n hi
nht thi
(FibroScan)

88 (78-94)

86 (81-90)

89 (8194)

73 (6679)

87 (8390)

26 (1934)

27 (2232)

42 (35-49)

92 (9194)

98 (9799)

98 (97-99)

tnh
(%)
(95% CI)
X ha r rt nhy (%)
(METAVIR
(95% CI)
>= F2)
c hin
(%)
(95%
CI)
Gi tr d
on dng
tnh
(%)
(95% CI)
Gi tr d
on
m
tnh
(%)
(95% CI)

78 (7184)

36 (2845)

68 (5976)

76 (7180)

60 (5069)

92 (9095)

84 (7590)

82 (7587)

57 (5261)

75 (6881)

74 (6978)

74 (6978)

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

WHO
4.1. Nhng bnh nhn cn iu tr
u 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 <= 2 ngi trng thnh),
nhng ln hn 30 tui, v c mc ALT bt thng n nh trong thi gian di v c chng
c cho thy c mc sao chp HBV cao (HBV DNA > 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 di
Liu 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 <= 2 ngi trng
thnh), v c mc ALT bnh thng n nh trong thi gian di v c mc sao chp HBV
thp (HBV DNA < 2000 IU/mL), bt k tnh trng HBeAg v tui. (Khuyn co mnh
m, chng c c cht lng khng cao)
Cn phi tip tc theo di tt c bnh nhn vim gan siu vi B mn tnh, nhng cn lu
nhng ngi khng tha nhng tiu ch quyt nh iu tr hoc khng iu tr trn,
xc nh c cn phi iu tr bng thuc khng virus trong tng lai ngn tin trin ca
bnh gan hay khng. Nhng ngi ny bao gm:
Nhng ngi khng b x gan c tui t 30 tr xung, c mc HBV DNA > 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 WHO
5.1. Liu php iu tr NA sut i
Tt 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 tr
Dng 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 <=
2 ngi trng thnh);
V c th c theo di cn thn trong thi gian di v kh nng ti hot ha;
V c chng c cho bit khng cn HBeAg v c chuyn ha huyt thanh thnh
anti-HBe ( nhng ngi lc u c HBeAg dng tnh) v sau khi hon tt t nht
mt nm iu tr b sung;
V kt hp vi mc ALT bnh thng n nh trong thi gian di, v mc HBV
DNA di ngng pht hin n nh trong thi gian di.
(Khuyn co c iu kin, chng c c cht lng khng cao)
5.3. Ti iu tr
Bnh c th ti pht sau khi dng iu tr vi NA. Khuyn co ti iu tr nu c du hiu
chc chn v s ti hot ha (HBsAg hoc HBeAg tr nn dng tnh, mc ALT gia tng,
hoc HBV DNA trn ngng pht hin tr li). (Khuyn co mnh m, chng c c cht
lng khng cao)

6. Cc xt nghim dng theo di bnh vim gan siu vi B mn tnh

theo khuyn co ca WHO
6.1. Theo di din tin bnh v p ng iu tr bnh nhn vim gan siu vi B
mn tnh trc, trong, v sau iu tr
Cn phi theo di hng nm (t nht) cc xt nghim sau:
Mc ALT (v AST tnh APRI), HBsAg, HBeAg, v mc HBV DNA;
Cc k thut khng xm ln (im s APRI hoc FibroScan) nh gi x gan,
nhng ngi khi iu tr khng b x gan;
nhng ngi ang c iu tr, cc xt nghim ny phi c thc hin thng
xuyn v mi ln khm bnh.
(Khuyn co mnh m, chng c c cht lng tng i cao)
Cn theo di thng xuyn hn:
nhng ngi cha n mc phi iu tr bng liu php khng virus: Cn theo di
thng xuyn hn nm c din tin bnh : nhng ngi c mc ALT bt
thng gin on hoc mc HBV DNA dao ng gia 2.000 IU/mL v 20.000

IU/mL v ngi ng nhim HIV. (Khuyn co c iu kin, chng c c cht

lng khng cao)
nhng ngi ang iu tr hoc nhng ngi ang theo di dng iu tr: Cn
theo di thng xuyn hn khi ang iu tr (t nht mi 3 thng nm iu tr u
tin) : nhng ngi c bnh din tin nng (x gan cn b hoc mt b), trong
nm iu tr u tin theo di p ng iu tr v s tun th iu tr ca bnh
nhn, nhng bnh nhn ng nhim HIV, v nhng ngi sau khi dng iu tr
(Khuyn co c iu kin, chng c c cht lng khng cao).

6.2. Theo di c tnh ca tenofovir v entecavir

Theo di chc nng gan (mc creatinine huyt thanh, v tnh mc thanh thi creatinine
(CrCl)/t l lc ca cu thn c tnh (eGFR) theo cng thc Cockcroft-Gault)) v nh gi
nguy c gy ri lon chc nng thn tt c nhng bnh nhn trc khi bt u iu tr
bng liu php khng virus.
Theo di chc nng thn hng nm nhng ngi c iu tr lu di bng tenofovir hoc
entecavir, tr em cn theo di thm s pht trin mt cch cn thn.
(Khuyn co c iu kin, chng c c cht lng khng cao)
6.3. Theo di ung th biu b gan (HCC)
Theo di nh k HCC bng k thut siu m bng v xt nghim alpha-fetoprotein mi
su thng c khuyn co cho:
Nhng ngi b x gan, bt k tui v cc yu t nguy c khc (Khuyn co mnh m,
chng c c cht lng khng cao)
Nhng ngi c tin s gia nh b HCC (Khuyn co mnh m, chng c c cht lng
khng cao)
Nhng ngi trn 40 tui, khng c chng c b x gan (hoc da trn im s APRI <=
2), v c mc HBV DNA > 2.000 IU/mL (Khuyn co c iu kin, chng c c cht
lng khng cao).
Knh trnh Tng Gim c xem xt.

Ni nhn:
-

Nh trn;

DLS;

TNG GIM C

G. QLCL

BS. Tn Tht Qunh Trung

CN. Phm Thanh Phong