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
i;
> i
Ba6c
DAU DANH GIA HIEU QUA DIEU TRj ENTECAVIR TREN
BENH NHAN VIEM GAN VIRUS B MAN TINH HBeAg
DUONG
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
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
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
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
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
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
(-}:
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
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
^, , ^'
''"' '''•' ^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
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
. , .
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 =
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
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
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
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
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%
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
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;
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
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,
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
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