Bước đầu đánh giá hiệu quả điều trị Entecavir trên bệnh nhân viêm gan virus B mạn tính HBeAg dương tính và HBeAg âm tính

TCNCYH
66 (1) - 2010
weeks.
Results:
lhi>re
was no
cdlleclidn
of inflammatory cells at the lime of evaluation. At 4 weeks, lhe
vasc:ulari/'ation
and the invasion of fibroblasts were noted and at 8 weeks some new woven bone ardund
Ihe graft
were
fdiind.
Conclusion: there was no evidence of infection and
rejection,
fhe alldgraft
lenddii
lo
bone healing was
recogni/cd
with the same
manner
of autdgraft. . ;, . ,,
Keywords: allograft, experimental, tendon graft, tendon to bone healing
i
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DAU DANH GIA HIEU QUA DIEU TRj ENTECAVIR TREN
BENH NHAN VIEM GAN VIRUS B MAN TINH HBeAg
DUONG

TINH
VA HBeAgAMTINH
. ,
Nguyen Cong Long, Dao Van Long, Biii Xuan Trfldng, Le Van Anh
Khoa Tieu hda - Benh vicn Bach Mai I la Ndi
Muc tieu: dinh gii tie dung, tinh an toin ciia Entecavir trong dieu trj
vlSm
gan virus B man tinh cd
HlieAg(+) va
HBeAg(-).
Doi tUgng va phuang phap
nghien
cdu: nghien cifu tie'n cdu 47 benh nhim dtfdc
chan doan viem gan virus B man linh (VGVRB) ehia hai nhdm ilBeAg(+) vi
HBeAg(-)
dtfgc dieu trj Hntecavir
i>,')
mg/ngay trang thdi gian
12
tuan. Kit qua: dac diem tudi nhdm ilBeAg(-) caa han nhdm HBeAg(+), tdn
thuang md henh hgc nhdm
HBeAg(-)
nang ban nhdm HBeAg(+)
vdi
chi so viem
10,1
± 2,8 so
vdi
9,6 ± 2,2,
chl sd xa 2,78 ± 1,8 so

vdi
1,8
±
1,3
diem
mac
dii
nong do HBV DNA d nhdm HBeAg(+) eao ban nhdm
IIBeAg(~)
8,29 ± 0,87 sa vdi 6,23 ± 1,62
lagcaples/ntl.
Nong do HBV DNA giam > 2 logcopies/ml sau
12
luan
dieu
trj hntecavir 0,5mg/ngay la
95,7%,
vdi nhdm
HBeAg(-i-)
la
94,1%
va nhdm HBeAg(-) li 96,7%.
Ndng do HBV DNA dat difdi ngifdng phit hien dat
J6,2%,
frung binh nong do HBV DNA giam 4,71 ± 1,8
logcoples/ml
d nhdm VCVRB HBeAg(+) vi - 4,84 ±
1,7
logcaples/ml
d nhdm VGVRB

HBeAg(-).
Ty le
chuyen dao huyet thanh d nhdm HBeAg(+) la
17,t)°/o,
binh
thifdng hai men gan ALT li
51,l"7o.
Cic tneu
chdng lam sing met mdi, chin an eai thien d
1U0%>
benh nhan, lic dung phu
ciia
thudc it gap, thudng nhe,
hay gap nha't la dau dau va
viem mui
hgng. Kit luan: lnlecavir li thud'c cd kha niing ifc che sU nhan len
ciia
virus tdt d ca hai nhdm viem gan virus B man tinh cd HBeAg(+) vi
HBeAgi-l,
hinh thudng bail men gan va
ehuyen dao huyet lhanh
l-IBeAg
dat ly le kha cao, cai thien tneu chdng lam sang
tdt.
It lac dung phu, nen
hfa chgn la thudc dau tay trong
dieu
trj viem gan virus
R
man tinh.

Tii khoa: viem gan virus B, entecavir
I. DAT
VAN
DE dflpc xdp vao vung dai djch nhiein LIBV vdi
Hien nay
thc'^
gidi cd tren 350 trieu ngfldi phfldng thflc lay truyin chu ye'u tfl me sang con,
nhiem HBV man tinh |9|, so' benh nhan nhiim ddng thdi LIBV la nguyen nhan chinh gay
vii^m
LIBV man tinh cd HBsAg dflong tinh tai Trung gan man, xo gan va ung thfl gan.
lOieu
trj viem
Qucdc
va khu vflc
t3dng
Nam chau A trong dd cd gan virus B cd nhiiu tien bp trong thap ky qua.,
Vii^t
nam chiem khoang 50% tdng sd benh
nhin
Interferon - alpha dflpc xem la thud'c dau lien
tri§n
tdan
\hi
gidi.
Tai Viet Nam, ty le nhiim difpc cdng nhan trong dieu trj, nhifng thudc
HBV cd HBsAg
difong
tfnh cao tren 8%
din
sd nhdm cytokine nay chl cd

hicMi
qua khoing 35%
TCNCYH
66 (1) - 2010
bc^nh
nhan khi difpc dieu tri, va nhiiu tac dung
phu |13|. Lamivudine, met
din
chat chit ddng
dang cytdsine la mpt thudc udng ra ddi dau tien
Cd hieu qua flc chi virus tad trong thdi gian
ngln
18].
Tuy nhien theo thdi gian hien tifong
khang Lamivudine xuit hien vdi ty le cao tren
motif
YMDt3
|6]. Theo ddi hieu qua dieu trj lau
ciai
tren benh nhan cd HBeAg am tfnh vdi
Adeldvir, thud'c
iifj'ng
thfl hai difdc cdng nhan
Irong dieu trj viem gan B, cho thiy ty le khang
kieu gen sau 5 nam la 29%
111],
va mpt so'
nghic^n
cflu khac blo do khoing 20 - 50% benh
nhan diiu trj Adefovir

lOmg
khdng cd dap flng
lien phat 110]. Entecavir la mpt chit ddng dang
dddxyguandsine
cn hieu Iflc gip
lien
300 lln sd
vdi Lamivudine trdng in
vilrd
11,
12|. Entecavir
i?(
ch("''
ca ba khau treng qua Irinh nhan len HBV
DNA bad gdm qua trinh lao chit mdi HBV DNA
polymerase,
qua.trinh
sao
eh(§p
ngflpc tao chudi
I IBV DNA am va
qui
trinh tdng hpp chudi HBV
DNA difdng 12]. Hai nghien cflu qud'c te' thfl
nghiem lam
sing
phase III cho thiy Entecavir
li(^u
0,5 mg/ngay trong 48 tuan dat hieu
qui

cao
vc^
di thien md benh hpc, virus va
hoi
sinh tren
benh nhan
HBeAg(-i-)
va
PlBeAg(-)
so vdi
Lamivudine, cung nhfl tfnh an loan cua thud'c va
khdng xuit hien khlng thud'c neu khdng tren nin
l)enh nhan trifdc dd da cd dot bien khang lai
Lamivudine, rtL180M/V va rlM204V/l/S 17, 12J,
Entecavir difpc FDA Lloa
Ky
cdng nhan diiu trj
viem gan virus B thang 3/2005. CJ Viet Nam cho
dcMi
nay chifa cd nhieu nghien cflu dly du danh
gia hieu
qui
dieu trj cua Entecavir treng diiu trj
viem gan B man. Dd vay chflng tdi lien hanh
nghien cflu nay vdi muc
tieu:
Danh gia hieu qua Entecavir trong diiu tri
viem gan B man tinh tbong qua cac cbi sd lam
sang va can lam sang ALT, ndng do HBV - DNA
d cac thdi diim trudc va sau 12 tuan va danb

gia tac dung phu cua thudc.
II.
DOI TU'ONG VA
PHGONG
PHAP
NGHIEN CL/U
1.
Do'i tuong nghien cu'u
Nghien cflu 47
benh
nhan c:d chan ddan viem
gan virus B man linh
difa
tren kham lam sang,
can lam sang va sinh thiet gan lai khea Tieu hea
benh vien Bach Mai tfl thing 7/2008 den thang
7/2009. Tieu chuin chpn benh nhan viem gan B
man linh tren
16
tudi,
LIBsAg difdng
tinh
tren 6
thing,
ndng dp ALT tang cad > 1,3 lan mflc
binh
thifdng (lien
tiic
hdac ngll quang), ndng
d() 1

IBV -
DNA > 5
Idgcdpies/ml
vdi nhdm HBeAg(+), ndng
dp HBV - DNA > 4
Idgcopics/ml
vdi nhdm LIBeAg
(~),
sinh thiet gan lam md benh hpc cd tdn thifdng
gan man tinh danh gia thed thang diem Knddell
sfla ddi.
f.dai
trif
benh nhan cd lieu cau thip
<
90.000/mm\
Creatinin huyet thanh > 1,5 lan sd
vdi mflc binh thifdng, benh nhan
nghicMi
rifOu,
cd
bieu hien xd gan mit bu, ddng nhiem vdi viem
gan virus C, HIV, benh nhan cd diiu trj cac thudc
khang virus khlc, thudc dieu hda mien
dich,
certi-
cdid
trdng vdng 6 thing trifdc diiu trj, php nfl cd
thai,
dang cho con bu. "fhudc sfl dung Entecavir

biet dfldc Baraclude cua cdng ly difdc pham BMS
(Bristdl - Myers - Squibb), lieu lifdng 0,5 mg/ngay,
ud'ng dch xa bfla an 2 gid. Danh gia trifdc va sau
12
tuln dieu trj cac: trieu chflng lam sang va can
lam sang bao gdm Al f,
ASF,
Bilirubin, Creatinin,
HBeAg va Anti - HBe va ndng dp HBV DNA.
2.
Phfldng phap nghien cflu
Khang nguyen HBeAg va Anti - I
IBo
xlc dinh
bang ELISA, ndng dp HBV - DNA xac dinh blng
Real
-
time PCR, ddn vi
tinh
Idgcdpies/ml.
ALT,
AST, Creatinin difdc xlc djnh tai khda Hda sinh
benh vien Bach Mai. Sinh thiet gan difdc lien
hanh tai khda Tieu hda benh vien Bach Mai,
dinh
gil md benh hpc tai khoa
Giii
phau benh
benh vien Bach Mai theo phan loai Knodell sfla
ddi vdi chl sd viem cd gia trj tfl

0-18
diem,
chi
TCNCYH 66 (1) - 2010
so xd Cd gia
Iri Ifl
0 6 tuy mflc (.16 tfl nhe den 78,8%, chan an 59,6%, ndng dp
fIBV
DNA 7,03
nang,
••.,,•:
± 1,68
Idgcdpies/ml,
ALL
trung binh 373,3 ± 504
.,
V-'.
I-
-T-
U/L, sinh thiet gan chin ddan
difPc
tien hanh tren
3. Xfl ly so
lieu - s
23 BN vdi trung binh
chi
sd viem
10
± 2,68; chl
Sail

khi Ihu thap day du dc sd lieu , qua trinh
xu ly difpc lam tren may linh vdi phan mem xfl ly
sd lieu SPSS
11.5
version, gil tri P < 0,05 difpc
xac djnh la mflc khac biet co y nghla thdng ke.
sd xd 2,78 ± 1,8 trdng dd ty le xd hoa > 3 diem
(xd bac clu) chiem 56,5% Tudi trung binh nhdm
HBeAg{+) la 33,2 ± 12,2 (20 - 73 ludi), nhdm
HBeAg{-) la 44,7 ± 10,9 (24 - 65 tudi), ndng dp
III.
KET QUA
^If^y
Q,^^
(^i^i,.,g
binh
d nhdm HBeAg(-t-) la 8,29
+
Sd lieu bang 1, 2 chd thay tdng sd 47 BN 0,87 logcopies/ml va d nhdm HBeAg(-) II 6,32 ±
(benh nhan) nghien cflu 76,6% la nam va 33,4% 1,62 logcopies/ml. Nong dp ALT trung binh d
nfl,
tudi tnmg binh 40,5 ±
12,5
tudi.
Cac trieu nhdm
HBeAg(-i-)
la 281,1 ± 338,8 U/L va nhdm
chflng lam sang hay gap nhit la met mdi chiem HBeAg(-) la 425,5 ± 576 U/L.
Bang 1. Dac diim lam sang nhom benh nhan nghidn cdu
(-}:

Am linh, (+): DifOng tinh,
IfP =
0,0017
Dac diem lam sang
FJac dic^'m . .,.
Dau ha ,
^
nhdm phan
, ,
Nam . Nfl Met
Chin sifdn
Vang
_
(nam) ,. , ,. , Gan to
tich moi
an
phai
da
Chung d
hai nhdm
(N =47)
40,5 ±12,5 36/47 11/47 37/47 28/47 9/47 9/47 3/47
(20-73) (76,6%) (23,4%) (78,7%) (59,6%) (19,1%) (19,1%) (6,4%)
UU\T]
)
33,2
±12,2 11/17
.^J^l
13/17
9/17

1/17
2/17
1/17
''''^ (20-73)«
(64,7%)
'"
(76,5%) (52,9%) (5,9%) (11,8%) (5,9%)
(N =
1
7)
IIB'^A'J"(
)
'^'*'7±10,9
25/30
J/^Z)
24/30 19/30 8/30 7/30 2/30
\''"^„;
(24-65)«
(83,3%)
^'
(80%) (63,3%) (26,7%) (23,3%) (6,7%)
(N
=;
30)
Chi sd viem trung binh 9,6 ± 2,2 d nhdm VGVRB (viem gan virus B) I IBeAg(+) va 10,1 ± 2,8 d nhdm
VGVRB HBeAgI ),
chi
sd xa 1,8 ± 1,3 d nhdm HBeAg(+) vi 2,78 ± 1,8 d nhdm HBeAg(-).
Dap flng ve trieu chflng lam sang sau
12

tuan dieu trj
f
Cac trieu chflng met mdi, chan an va dau ha sifdn phai diu thuyen gilm
100%
so vdi tnfdc dieu trj,
trieu chflng vang da gilm d 88,9%.
Dap flng vdi virus
Ndng dd HBV DNA gilm > 2 logcopies/ml sau
12
tuan diiu trj d 47 benh nhan la 95,7%
IBIng
3].
94,4%
d nhdm
HBeAg(-^)
va 96,7% d nhdm HBeAg(-) dat dflpc ndng dp HBV DNA giam > 2 logcopies/
ml hdac dfldi ngfldng phlt hien blng phifpng phap real time PCR sau
12
tuan dieu trj. Trung
binh
ndng
(Id
HBV DNA giam - 4,84 ± 1,75
Idgcopies/ml
d cl hai nhdm, va
-
4,71 ± 1,8
logcdpies/ml
d nhdm
10

TCNCYH
66 (1) - 2010
VGVRB
ITBeAg(+)
va 4,84 ± 1,7
Idgcdpies/ml
d nhdm VGVRB
hlBeAg(-).
Sau
1
2 luan dieu trj 47 BN Ihi
36,2%
bcMih
nhan dat giam ndng dp HBV DNA difdi ngifdng phat
hien,
1
1,8% va 50% xet rieng d
hai
nhdm VGVRB HBeAg(+) va VGVRB
LIBeAg(-)
vdi p = 0,002,
,,,
.
Bang 2. Dac diim can lam
sang
nhdm benh nhan ngbien cdu
,
Dac diem can lam sang
Oac diem
^, , ^'

r-i >

^
Chl so
^,
,,
,,
Chl so xtf
nhom
HBVDNA
ALT AST Bilirubin TP
Chi
so xtf
^,^r
viem >
3
>
5
phan
tich
f'"T"
7'«3-U.«
'''na*
'.'tY;
f;n.'
1°*2,68
^f/
13/23 5/23
'^""'^°'^^
(4-9,55)

''"' '''•' ^20,5
1,8
(N=47)
'
(52-2381) (35-1632) (6,8-490)
(0-6)
Nhiim
281,1 ±
179,5
± ,. 1,8
+
,
8,29
±0,87-*
',
,„'
20,6 + 20,1 9,6 + 2,2' '
^,
l/S-"
0/5
zx:
"-
.:,•:",?;.,
.^'L
-^-»"
— .,'::,
««-
-
Nhdm
42

55+ 101+ 31 +
6,32 +
1,62'*
•'
247 + 368,8
96,9
±147 '
12/18'
5/18
{M = m ''-''''' (52-2^81)
'^^5-^"^'
'^'^-^^O'*^'
^5-'l5) (o'-6) '^^'^o/.,)
,27,8%)
*P =
0,003,
'P =
0,134,
*P
=
0,606,
'P
= 0,431,
'P
=
0,065;
VGVRB: viem gan virus B, IP: toin phan.
Bang 3. Ty IS benb nhan cd dap dng vdi virus, boa sinh thdi diem sau diiu trj
12
tuan

Dap u'ng can lam sang sau
12
tuan dieu tri
HBVDNA
Trung binh
,
,
,
, Trung ,
„,
,.,
''
HBVDNA Binh Binh ,
.*' Chuyen
dao
Oac diem giam
> 2
HBVDNA
., binh , - , ,
',
, , . , ,
Biam
< 69
thfltfne
hoa
thfltfng
hoa huyet thanh
nhom
loecopiL's/ml giam
. , .

,
Bilirubin
, . ,, , ,^ . '„
,, .
, n cop.es/ml Air
AST .,
HBcAg
sau
phan
tich
hoac < 69 (
oecopies/m
), ,
,
,
,
,
eiam , ,,
copies/ml mean ± SD (pmol/L)
,'^'1',^''
4.5/47 -4,84
±1,75 17/47
24/47 25/44
13/14
3/17
jN-I/i^
(95,7%) (36,2%)
(51,1%)
(56,8%) (92,9%)
(17,6%)

Nhom
l-ILk'Ag
(+)
(N = 17)
.16/17
-4,71
±1,8' 2/17
9/17 9/17
2/3
3/17
(94,1%)
(11,8%)'*
(52,9%) (52,9%) (66,7%) (17,6%)
Nhdm
HBeAg
(-)
(N = 30)
29/30 -4,84 + 1,7' 15/30
15/30
19/30
11/11
(96,7%) (50%)* (50%) (63,3%) (100%)
•'
Theo Td cht'fc Y te The
gidi:
ALT dtfdi 1,25 x mifc
binh
thtfdng,*P =
0,002,
*P =

0,467.
'' Mi't HBeAg vi dat duac Anti - Hbe dtfang tinh.
TCNCYH 66 (1) - 2010
Dap u'ng hoa sinh
100%
cd ndng dp ALT luc dau > 1,3 lan so vdi
mflc binh thfldng, ty le binh thfldng
hoi
ALT ehung
eho 2 nhdm sau
12
tuln dieu trj II
51,1%,
d nhdm
VGVRB
HBeAg(-H)
la 52,9% vl nhdm VGVRB
HBeAg(-)
II
50%. Ty le binh thfldng
hoi
men gan
AST sau
12
tuan tren 47 BN la 56,8%. 6 nhdm
HBeAg(-i-)
la 52,9% va nhdm HBeAg(-) la 63,3%.
Tac dung phu
CIc bieu hien
tie

dung phu tren lam sang hay
gap II dau
diu
chiem 12,8% va viem mui hpng
chiem 10,6%, khdng cd
tie
dpng phu nghiem
trpng
phii
ngflng diiu tri. Bung phlt men gan
khdng gap trifdng hdp nao {bleu do 1).
14.00%
12.00%
10.00%
8.00%
6.00%
4.00%
2
00%
0.00%
a
,JZ^,
Dau dau
Viem mui
Dau bung Nhip
hpng nhanh
la long Tang ALT
Biiu do 1. Tong bgp tac dung phu trSn lam sang va
can lam sang
IV. BAN LUAN

Muc tieu chfnh cua diiu trj viem gan B man
tfnh hien nay la flc che
qui
trinh
nhin
len cua
virus mpt cleh bin vflng, ngan chan
qui
trinh
tien trien cua benh, gilm ty le bien chflng va tfl
vong.
Viem gan B man tfnh dflpc chia lam hai
nhdm chinh, nhdm HBeAg dfldng tfnh va nhdm
HBeAg am
tfnh,
HBeAg am tinh cd the xuit hien
tfl nhien hoac xly ra do hien tflong dot bie'n vung
precore vl core promoter. Benh
nhin
viem gan
HBeAg am tinh cd
qui
trinh tien trien tdi xd gan
va ung thfl gan nhanh hdn so vdi nhdm HBeAg
dfldng
tfnh,
hdn the nfla
khi
nang
dip

flng vdi
thud'c khlng virus khae nhau gifla hai nhdm(7].
Nghien cflu 47 BN trong dd VGVRB
HBeAg(-H) 1
7
BN (36,2%), VGVRB HBeAg(-) 30 BN (65,8%) vdi
dac diem tudi nhdm HBeAg(-) 44,7 ± 10,9 tudi
cao hdn so vdi nhdm
HBeAg(-i-)
33,2 ±
12,2
tudi,
ket
qui
nly cung tflong tfl dc
tic
gil trong nfldc
11,
4]. Ngoli trieu chflng lam
sing,
djnh lfldng
virus,
hoi
sinh de chan doln viem gan B man
tinh,
sinh thiet gan lam md benh hoe 23 BN
(48,9%) thiy mflc dp viem gan d nhdm HBeAg(-)
nang hon nhdm cd
HBeAg(-i-),
chi so viem theo

phln loai Knodell sfla ddi 9,6 ± 2,2 diem d nhdm
HBeAg(-i-)
thip hpn so vdi 10,1 ± 2,8 diem d
nhdm HBeAg(-), chi sd xd d nhdm HBeAg(-) la 3,1
± 1,7 diem nang hdn so vdi nhdm
HBeAg(-i-)
la
1,8 ± 1,3 diem. Ndng dd HBV - DNA trung binh
thdi diem bat dau dieu trj d nhdm
HBeAg(-i-)
la
8,29 ± 0,87 logcopies/ml eao hdn so vdi nhdm
HBeAg(-) la 6,23 ± 1,62 logcopies/ml, neu so
sinh
vdi ele nghien cflu qud'c te cua Lai CL
[12],
Chang TT [7] thi ndng dp HBV DNA nhdm
HBeAg(-t-)
la 9,62 ± 2,01 logcopies/ml, nhdm
HBeAg(-) la 7,6 ± 1,8 logcopies/ml cao hon so vdi
nghien cflu nay, nghien cflu trong
nifde
cua Mai
Hdng Blng[1 ] ndng dp trung binh HBV DNA cl 2
nhdm trfldc dieu trj II 7,1 ± 1,6 logcopies/ml
tflong tfl nghien cflu eua chflng tdi. Men gan ALT
trung binh d nhdm
HBeAg(-i-)
281,1 ± 338,8 U/L,
nhdm HBeAg(-) 425,5 ± 576 U/L

khi
cao so vdi
dc nghien cflu trong nfldc Dinh Da Ly
Hflong
[18]
thi gil trj trung
binh
ALT II
140
U/L d nhdm
HBeAg(-). Tieu chuan lfla chpn benh
nhin
trong
nghien cflu ndng dp ALT > 1,3 lln mflc
binh
thfldng vl ndng dp HBV DNA > 4 logcopies/ml
vdi nhdm HBeAg(-) va > 5 logcopies/ml vdi nhdm
HBeAg(-i-)
tflong tfl nhfl
tic
gil Lai CL, Chang TT
[7,
12], ngfldng ALT dfla vao diiu trj thip hon so
vdi ele
tie
gil trong nfldc thfldng bat dau dieu trj
vdi ngfldng ALT > 2 lln mflc binh thfldng [1, 4].
Dinh
gil ket qua diiu trj dfla vao dap flng virus,
hoi

sinh,
chuyen
dio
huyet thanh HBeAg vdi
12
TCNCYH 66 (1) - 2010
nhdm IIBeAg(+), va di
thicjn
md benh hpc, tuy
nhi(^n
(lanh gia clap flng di
lhic?n
md benh hpc se
bad cao sau
Ihcd
ddi dieu Iri 48
luan,
Kc'n
qua dic>u trj sau
1
2 luan chd thay dap flng
virus nhanh (ndng do virus giam > 2 logcopies/ml
hoac giam difdi ngu'dng phat
hi(?n)
d cl hai nhdm
HBeAg(h)
va
|-IB(-Ag(-)
la 94,1% va 96,7% cdn ly
le dap flng cluing chd ca 47 BN la 95,7% ke'l

qui
nay tifdng tfl ket qua cac nghien cu'u khac tren the
gidi va trdng nifdc 13, 4,
7],
Ndng dp gilm HBV
DNA trung
binh sail
12 luan dieu tri dat ket qua
cad 6 ca hai nhdm trdng dd giam 4,71 ± 1,8
logcdpies/ml dnhom
HBeAg(+) va d nhdm HBeAg
(-)
la 4,84 ± 1,7 Idgcopies/ml ne'u so sanh vdi
ki'-'l
(|ua
(lic'ii
Iri sau 48 tuan lrong nghien ci'fu
ciia
Lai
CFU 21
vdi nhdm
|-IBeAg(-)
giam - 5,0 + 1,7
ldgcdpic;s/ml
va Chang
1717]
d nhdm
LIBeAg(-i-)
giam 6,9 ± 2,0 Idgcopies/ml. Ndng dp HBV
DNA dat dudi ngifdng phat hien

11,8%
va 50% d
nhdm IIBcAg(+) va HBeAg(-) khac biet nay cd y
nghla thdng kc, ddi chieu vdi ket qua
nghiijn
cflu
Clia iai CII, Chang TF sau 48 luan diiu tri dat
ngifdng khdng phat hien difdc virus vdi nhdm
HBeAg(-) la 90% va 67% d nhdm HBeAg(-).
Ty le binh thfldng hda men gan ALT sau 12
thang diiu tri chung chd d hai nhdm la 51,1%
Irong dd d nhdm
HBeAg(-F)
52,9% va d nhdm
LIBeAg(-) 50%, ly le binh thfldng
hdi
men AST la
:i6,8%
chung cho ca hai nhdm, Fy le dat binh
Ihifdng
hoa men gan
ciia
chung tei khdng cao so
vdi cac nghien cflu d trong nifdc cung nhfl qud'c te
vi thdi gian theo ddi mdi difpc 12 tuan so vdi
nghicSn
cflu cua Chang FT ly le binh thifdng
hoi
men gan sau 48 tuan'la 68% d nhdm HBeAg(+) va
78%

d nhdm HBeAg{-) trong nghien cflu cua Lai
CH.
Ndng dp Bilirubin loan phan giam so vdi
tnfdc dieu Iri dat ldi 92,9%, lrong dd nhdm
flBeAg(+)
dat ty le 66,7%, nhdm HBeAg(-) dat
100%
gilm ndng dp Bilirubin toan phan qua
12
luan dieu tri. Ty le chuyen dao huyet thanh
HB(>Ag
trong nhdm VGVRB FIBeAg(+) la
17,6%
sau 12 luan dieu tri
kel
qua nay so vdi mpt so
nghiiMi
cflu lrong nu'dc
ciia
lac gia Frinh Ihi Ngdc
14]
theo ddi sau 48 tuan (li(''u
Irj
thi ly
k"^
chuyen
dad
huyc'n
lhanh d luan 24 la
10%

va luan 48 la
26,7%,
vdi
nghicjn
ct'fu
qu(")'c id ciia
Chang va
cdng SLf theo ddi sau 48 tuan la 21%. Cac trieu
chflng lam sang difpc di thien
lii't
sau 12 tuan
diiu trj, trieu chflng met mdi chan an, dau ha
sifdn phai cai thien d
100%
benh nhan, vang da
di
thii'n
88,9% sd benh nhan, chd thiy
hie^u
qua
cua thud'c tren lam sangkha cae,
l ntecavir
la m()l
Ihudc
(lung nap
td'L
tac dung phu khdng dang kc":',
khdng Cd tnfdng hop nad
trdng
nghien

ci'i'ii
phai
dflng diiu tri, Flien tifpng bung phat men ALF
kheng xly ra sau
12
tuan diiu trj,
ke[
qua dieu trj
Clia entecavir cung an toan va dung nap td't nhfl
dc nghien cflu trong nifdc va qudc te 11, 2, 7\.
V. KET LUAN
Entecavir la thudc cd
khi
nang flc che virus tdt
d cl hai nhdm viem gan vims B man tinh co
HBeAg(+) va HBeAg(-), binh thifdng
hoi
men gan
va chuyen
did
huye't thanh HBeAg kha cae, di
thien trieu chflng lam sang tdt, ft
tic
dung php,
nen lfla chpn la thud'c dau lay trdng diiu tri
vic">m
gan vims B man
tfnh,
TAI
LIEUTHAM

KHAO
1.
Mai Hong Bang,
le
HuU Song (2008).
Nghien cflu sd sanh hieu quan cua Entecavir va
Lamivudine trong diiu trj viem gan virut B man
tinh.
Tap
chi
Gan Mat Viet Nam; 8
-
2008;
6-12.
2.
Banh Vu Dien (2007). Dfl lieu an loan va
hieu
qui
cua Entecavir. Tap chf gan mat Viet
Nam;
2 - 2007; 23 - 26.
3. Dinh Da ly Hfldng (2007). Ket qua
1
nam
dieu tri Entecavir cho benh nhan viem gan B man
tinh
HBeAg(-). Tap chf Gan Mat Viet Nam; 2 -
2007;
26-29.
• .

13
TCNCYH 66 (1) - 2010
4.
Trjnh Thj
Ngoe
(2009).
Bifdc
dau nhan xet
tac dung cua entecavir treng dieu tri benh nhan
vifcMn
gan virus B man
tinh.
Y hpc
lam sing
Benh
vien Bach Mai; 37; 26 - 33.
5. Pham Thj Thu Thuy, Ho Tan Dat (2007).
Hieu
qui
entecavir trdng diiu trj benh nhan sieu
vi B man tfnh khang Lamivudine. http://
www.drthulhuy.coin/rearch.
6. Allen Ml, Dcslauriers M, Andrews CW et
al.
(1998), Identification and characterization df
mutations in hepatitis B virus resistant to
lamivudine. Lamivudine Clinical
Investigatien
Group,
l-lepatdldgy;

27:
1670
- 77.
7. Chang TT, Gish RG, de Man R ct al.
(2006).
A
cdinparisdn
df entecavir and lamivudine
fer
HBeAg - pesitive chrdnic hepatitis B. N, Engl. J.
Med;
354: 1001-
10.
8. Dienstag JL, Schiff ER, Wright TL et al.
(1999).
Lamivudine as initial treatment for chronic
hepatitis B in the United States. N. Engl. J. Med.
1999;
341: 1256 - 63.
9. Fact
Sheet
WHO/204 Hepatitis B. 2000.
Geneva, Switzerland: World Health
Organizatien,
2003;
10-9.
« ,. :•
10.
Fung S, Chae HB, Fontana R et al. (2006).
Virdldgic

respcnse
and resistance to adefovir in
patients with chronic hepatitis B. J. Hepatol; 44:
283 - 90.
• i ' •
.
•
11.
Hadziyiannis S, Tassopoious N, Heathcote )
ct al. (2006). Long - term therapy wilh adefovir
dipivoxil for LIBeAg - negative chrdnic hepatitis B for
up td 5 years. Gastrdentereldgy ;
1
31:
1
743 - 51.
12.
Lai CL, Shouval D, Lok A et al. (2006).
BEHoLD AI463027 Study Group.2006. Entecavir
versus lamivudine
fer
patients with HBeAg
negative chronic hepatitis B. N. Engl. J. Med; 354:
1011
-20.
13.
Wong DKH, Cheung AM, O'Rourke K,
Naylor CD, Detsky AS, Heathcote |.
(1993).
Effect

of alpha - interferon treatment in patients with
hepatitis B e antigen - pesitive chronic hepatitis B. A
meta - analysis. Ann. Intern. Med;
119:
31
2 - 23.
Summary
PRELIMINARY EVALUATION OF ENTECAVIR IN THERAPY HBeAg - POSITIVE AND
HBoAg
- NEGATIVE CHRONIC HEPATITIS B PATIENTS
To evaluate clinically the efficacy and safety of entecavir in Vietnamese patients with chronic hepatitis
B. Methods: A prospective analysis in 47 Vietnamese chronic hepatitis B patients, the population study
was divided in to
tvJo
groups HBeAg positive and ElBeAg negative were treated with 0.5 mg entecavir
daily for 12 weeks. Results: Mean age of HBeAg(-) group was higher than that of HBeAg(+) group,
histologic characteristics of HBeAg negative group was more severe than HBeAg positive group, with
necroinflammatory score
1
0.1 ± 2.8 vs. 9.6 ± 2.2, and fibrosis score 2.78 ±
1.8
vs.
1.8
±
1.3,
respectively,
although HBV DNA level in LIBeAg positive group greater than that of HBeAg negative
greiip.
After 12
weeks df treatment with 0,5 mg entecavir daily, 94.1% and 96.7% df patients achieve the primary efficay

endpdint (a reduction from baseline in HBV DNA df > 2
Idgcdpies/ml
or to < 400 copies/ml by PCR assay
al week
12),
respectively, 36.2% of patients achieving undetectable HBV DNA in both treatment groups.
Mean changes from baseline in LIBV DNA were - 4.71 +
1.8
logcopies/ml
and
~ 4.84 ±
1.7
logcopies/ml
for the HBeAg positive and HBeAg negative groups, respectively and
normalizatidn
df alanine
amindtransferase levels was 51.1% in beth treatment
greups.
One hundred percent of patients in both
treated goups disappeared clinical symptdms such as fatigue and
anerexia.
The
indst cdmindn
side effects
were headache, nasdpharyngitis. Conclusion: Entecavir dffers td
cdntrdi
HBV replication in both group
14
TCNCYH 66 (1) - 2010
HBeAg positive and LIBeAg negative,

nermalizatidn
df alanine amindtransferase levels and HBeAg
serdcdnversidn
achieve relatively
high,
gddd clinical imprdvement and safety profile, this suggests
Ihal
entecavir shduld be
cdnsidered
as a primary therapy for HBeAg positive and HBeAg negative chronic
hepatitis B.
Keywords: Chronic hepatitis B, entecavir
,
MOI LIEN QUAN
GIQA
TINH DA
HINH
THAI CUA
INTERLEUKIN10
PROMOTER VA TINH TRANG VIEM THAN 6
;
BENH NHAN LUPUS BAN DO HE THONG
;!,.,
,
.1
Pham Dang Khoa
6(3 mdn
Mien
dich - Sinh ly benh - Trtfdng Dai hgc Y Hi Ngi
Muc tieu: khao sit mdi HSn quan giifa tinh da

hinh
thii cua Iterleukin
10
(IL -
10)
promoter vdi biiu hien
viem than d benh nhin lupus ban dd he thd'ng (SLE: systemic lupus erythematosus). Doi tugng va phuang
phap nghien cdu: ky thuit PCR - SSP (polymerase chain reaction - sequence specific primer) vdi ADN vi
pnmer dac hieu alen dtfgc sd dung de xie djnh tinh da hinh thii
ciia
IL -
10
promoter. Kit qua: khdng thay
md'i lien quan giifa tan suat cic kie'u gen ciia IL -
10
promoter
vdi
Hnh trang
viem
than d henh nhin SLE. Ket
luan: tinh da hinh thai
ciia
IL -
10
promoter cd the khdng lien quan tdi st/ xui't hien Ilnh trang viem than d
benh nhan SLE ngifdi Viet Nam.
Tii
khoa: IL-10, SLE, viem than
LDATVANDE
Co nhflng bang

ehifng
dang tin cay cho thiy
benh lupus ban dd he thdng (SLE: systemic lupus
erythematosus) la mpt benh ly phflc tap vdi sfl
tham gia cua nhiiu yeu to' gen hpc va mdi trfldng.
Dfla vao sfl tham gia cua mpt so' cytokin trong cd
che benh sinh cua SLE, ngifdi ta da phat hien
thiy sfl gdp phln cua dc yen to' gen hpc lien
quan vdi cytokin trong co che benh sinh eua
benh.
Interleukin -
10
(IL - 10) cd vai trd diiu hoa
dap flng mien djch te bao va djch lhe va la mpt
cytokin difpc ndi nhiiu tdi treng cac benh tfl miin
ni.
Tang ndng dp IL - 10 trong huyet thanh da
difdc
bao cao la cd lien quan vdi mpt sd benh tfl
miin,
trong dd cd SLE 12]. Mdi lien quan gifla
viec tao ra IL - 10 in vitro va kieu gen cua
promoter cung da difpc ndi den; dac biet, alen G
cua tinh da hinh thai G/A d vj trf nucleotid 1082
thiy cd lien quan vdi kieu hinh
sin
xuit IL-10
cao so vdi alen A 13].
Md'i lien quan gifla tinh da
hinh thii

cua IL10
promoter va SLE da difpc di cap den trong mpt
cdng
bd'trfldc
14]. Muc
tieu:
Khao sat mdi lien quan gida tinh da hinh thai
cua
I LIO
promoter vdi biiu bicn viSm than d
benb nhan SLE.
II.
DOI TU'ONG VA PHUONG PHAP
NGHIEN CL/U
1.
Do'i tfldng nghien cu'u
Benh nhan SLE dfldc chin doln va diiu trj tai
vien Da lieu Qudc gia. Tit d benh nhan cd it
15