26 Tap chi GAN MAT VIET NAM s6 16& 17-2011
Lien quan giiia kieu gen cua HBV vol HBeAg va nong do HBV DNA o" benh nhan viem gan vi-rut B man tinh
Preliminary studying of Hepatitis B virus genotypes in chronic hepatitis B patients
TRAN XUAN CHLTONG
Abstract
Aims: Studying the prevalences of HBV genotypes in chronic hepatitis B patients and their relation to HBeAg and HBVDNA level.
Methods: 81 patients were enrolled in this study from Jan. 2009 to Dec. 2010. Clinical, laboratory data were collected at the hospital- ized time. Sera were tested for HBeAg, HBV DNA quantitative. HBVgenotyping was made by Real-time PCR.
Results: Among 81 patients, 60.5% have genotype B, 26.7% have genotype C and 8.6%
have mixed genotype B-C Prevalence of symp-
toms (fatigue, anorexia, insomnia...) in geno- type C higher than genotype B. Genotype C patients have HBeAg positivity higher than genotype Bpatients (56% vs. 38,8%, p<0.05).
The rate of HBV DNA > 10^ copies/mL in genotype C group higher than genotype B group (36% vs. 28,6%, p > 0.05)
Conclusions: Most of patients have geno- types B or C Patients with genotype C have HBeAg positivity and may be related higher serological HBV DNA level than genotype B.
Tdm tat
Muc tieu: Nghien ciiu ty le cdc kieu gen cua HBV d benh nhdn viem gan vi-nit B man tinh vd mdi lien quan vdi HBeAg, ndng dp HBV DNA.
Phuong phdp: Nghien ciiu 81 benh nhdn VGVRB man tu 01.2009 din 12.2010. Cdc du kien lam sdng vd can lam sdng dugc thu thap trong thdi gian nhdp vien. Huyet thanh ciia cdc benh nhdn dugc tien hdnh xet nghiem HBeAg, ndng dp HBV DNA. Kieu gen cua HBV dugc xac dinh bang phuong phdp Real-time PCR.
Ket qud: Trong sd 81 benh nhdn, 60,5% cd kilu gen B, 30,9% cd kilu gen C, 8,6% cd kilu gen ddng nhiem B-C. Cdc trieu chiing met mdi.
chdn dn, mdt ngii ... chiem ty le cao hon d nhdm kieu gen C so vdi nhdm kieu gen B.
Khodng 50% bpnh nhdn kieu gen C, nhung chi 31% bpnh nhdn kieu gen B cd miic ALT cao hon 5 ldn gid tri binh thudng.
Kieu gen C cd ty le HBeAg (+) cao hon so vdi nhdm kilu gen B (56% so vdi 38,8%, p <
0.05). Ndng dp HBV DNA > 10^ copies/mL d nhdm benh nhdn kilu gen C cao hem nhdm kilu gen B (36% so vdi 28,6%, p > 0.05)
Ket lugn: Hdu het benh nhan cd kilu gen B hoac C. Kilu gen C cd ty le HBeAg (+) cao hon vd cd thl lien quan vdi tdng ndng dp HBV DNA huylt thanh so vdi nhdm kilu gen B.
I. Dat van de
Nghien ciiu ve cdc kieu gen, dudi kieu gen vd cdc dot bien cua HBV dang rit dugc quan tam trong nhung nam gdn ddy. Cdc kilu gen cua HBV cd lien quan den dien tiln vd tien
lugng ciia benh viem gan vi-nit B (VGVRB).
Chung ciing cd thl lien quan din miic dp ddp ling vdi dieu tri bdng cdc thudc khdng vi-nit ciiabenhVGVRB[2],[7].
Tmdng DH Y Dugc Hue
Tap chi GAN MAT VIET NAM s6 16& 17-2011 27 Cdc diu chi dilm nhdn len ciia HBV
(HBeAg, HBV DNA) ddng vai trd quan trpng trong tiln triln vd tien lugng ciia benh VGVRB man. Nghien ciiu vl su lien quan ciia cac kilu gen vdi cac ddu chi dilm ndy cho thdy rd hon vai trd ciia cdc kilu gen trong ddnh gid tinh trang benh vd tien lugng ciia benh VGVRB man.
Chiing tdi thuc hien de tdi nay nhdm 2 muc tieu:
1. Xdc dinh ty 14 cdc kieu gen cua HBVo benh nhdn viem gan vi-rut B mgn tinh
2. Tim hieu su lien quan giira cdc kieu gen cua HBV voi HBeAg vd HBVDNA.
II. Ddi tuOTig va phirong phdp nghien ciru l.l.Doi tirgrng nghien ciru
Doi tugng nghien ciiu la nhiing bpnh nhdn din khdm vd dilu trj tai Benh vipn Trudng DH Y Dugc Hui vdi chin dodn VGVR B man tinh trong khodng thdi gian tu 01.2009 - 12.2010.
Liia tudi: tu 15 tudi trd len.
Tieu chudn chin dodn VGVRB man:
- Tien sii phdt hien mdc viem gan B > 6 thdng.
- Xet nghiem huylt thanh: HBsAg(+) > 6 thdng hodc HBsAg(+) vd anti-HBc IgG(+).
- Xet nghiem cd transaminase tang tii 2 ldn
gia trj binh thudng trd len.
2.2.PhuOttgphdp nghien cuu:
Nghien ciiu tien ciiu
- Chpn benh nhdn thda man cdc tieu chuan chan dodn.
- Lap phieu theo ddi: cdc dir kien ve tien su, benh su, lam sang vd can Idm sdng.
Xdc djnh cdc kieu gen ciia HBV bdng ky thudt Real-time PCR. Thuc hien tren mdy Real-time PCR Stratagene Mx 3000 tai Phdng XN Khoa Vi sinh, Benh vien Trudng DH Y Duoc Hue.
i n . Ket qua
3.L Ty le cdc kieu gen cua HBV
Trong thdi gian tii 01.2009 -12.2010 chiing tdi cd 81 benh nhdn dugc dua vdo nghien ciiu.
trong dd cd 57 nam (chilm 70,4%) va 24 nii (chilm 29,6%). Tudi trung binh la 37,2 ± 14,9.
Bdng 3.1: Ty le cdc kieu gen cua HBV Kieu gen
B C B-C
n 49 25 7
%
60,5% (1) 30,9% (2)
8,6%
P p(i)(2) < 0.05 Nhdn xet: Kilu gen B chilm uu thl vdi 60,5%; kilu gen C chilm 30,9%; kilu gen hdn hgp B- C chi chilm 8,6%. Su khdc biet giua hai kilu gen B vd C cd y nghia thdng ke (p < 0.05).
Bdng 3.2: Lien quan voi trieu chimg Idm sdng
Trieu chiing Mat ngu
Chan an Met mdi Tieu van^ dam Vang mat, vdng da Gan ldn
Dau ha sudn phai 1 Bung bang
Kieu gen B n
24 32 28 16 15 9 8 2
%
48,9 65,3 57,1 32,7 30,6 18,5 16,3 4,2
Kieu gen C n
14 21 18 9 6 4 5 1
%
56 84 72 36 24 16 20 4
P
>0.05
<0.05
<0.05
>0.05
>0.05
28 Tap chi GAN MAT VIET NAM s6 16& 17-2011
Nhdn xet: Cdc trieu chiing thudng gap Id: mpt mdi, chdn an, mit ngii ... chilm ty le cao hon d nhdm kilu gen C so vdi nhdm kilu gen B. Su khdc nhau d 2 nhdm kilu gen cd y nghia thdng ke (P < 0.05).
Bdng 3.3: Lien quan giira kieu gen v&i ALT
Chiing tdi chi khao sdt 2 nhdm kieu gen B vd C. Nhdm kilu gen B-C cd so mau it nen khdng cd gid trj thdng ke.
Kieu gen B C
GTBT n
7 5
%
14,1 20
> 1 - 5 lan GTBT n
19 6
%
38,8 24
> 5 lan GTBT n
15 10
%
30,6 40
Khong XN n
8 4
%
16,3 16 Nhdn xet: Ty Ip cdc ndng dp ALT d hai nhdm kilu gen B vd C tuong duong nhau. 40% nhdm kilu gen C cd nong dp ALT cao hon 5 lan GTBT so vdi 30,6% d nhdm kieu gen B.
3.2. Lien quan giira cdc kieu gen vdi HBeAg vd HBVDNA
Bdng 3.4: Lien quan giira kieu gen voi HBeAg Kieu gen
B C B-C
HBeAg (+) n
19 14 4
%
38,8(1) 56(2)
57,1
HBeAg (-) n
30 11 3
%
61,2 44 42,9
P
p(l)(2) <0.05
Nhdn xet: Kieu gen C cd ty le HBeAg (+) cao ban so vdi nhdm kieu gen B (56% so vdi 38,8%, p < 0.05).
Bdng 3.5: Lien quan giUa kieu gen voi nong do HBV DNA
Cd 70 benh nhdn dugc xdc djnh ndng dp HBV DNA, trong dd cd 44 benh nhdn kieu gen B, 20 benh nhdn kieu gen C vd 6 kieu gen B-C.
Kieu gen B
C B-C
< lO'copies/mL n
16 5 2
%
32,7 20 28,5
<10*-10^copies/mL n
19 11 3
%
38,8 44 42,9
> lO'copies/mL n
14 9 2
%
28,6(1) 36(2)
28,5
P p(l)(2) >0.05
Nhdn xet: 67,4% benh nhdn kilu gen B vd 80% benh nhdn kilu gen C cd HBV DNA tdng cao hon 10^ copies/ml (p>0.05). Nong dp HBV DNA > 10^ copies/mL d nhdm benh nhdn kilu gen C cao ban nhdm kilu gen B (36% so vdi 28,6%, p > 0.05)
IV. Ban luan
4.1.Cdc kiiu gen cua HBVdbenh nhan VGVR B mgn tinh
Theo ket qud d bdng 1, Kilu gen B chilm
uu thl vdi 60,5%; kilu gen C chilm 30,9%;
kilu gen hdn hgp B-C chi chilm 8,6%. Su khdc biet giua hai kilu gen B vd C cd y nghla
Tap chi GAN MAT VIET NAM so 16& 17-2011 29 thdng ke (p < 0.05).
Theo Nguyin Cdng Long vd cdng su d Hd Ndi kilu gen B chilm da sd vdi 70,7%, kilu gen C chilm ty le thip hon vdi 29,3% [3]. Theo Ddng thi Hodi An thi phin ldn benh nhan VGB man cd kilu gen B (77,8%); kilu gen C chi chilm 21,3% [1]. Nghien ciiu gin day ciia Hodng Tien Tuyen cho thiy ty le cdc kilu gen d benh nhdn VGB man lin lugt Id B: 46,5%, C: 50,7% vd B-C: 2,8% [4]. Nghien ciiu cua Nguyen H. Long vd cs d nhiing ngudi My goc Viet tai Hoa Ky cho thiy hai kilu gen B vd C vdn Id chu ylu. Kilu gen B chilm 74% vd kilu gen C chilm 24% [7].
Nhu vay theo tit cd cdc tdc gid thi cdc kilu gen chii yeu d benh nhdn VGVRB man ngudi VietNamldBvdC.
Yuen d Hdng Kdng cho thiy cd 32,5% cd kieu gen B trong khi 62,5% cd kilu gen C. Kit qud ndy phu hgp vdi cdc nghien ciiu d Trung Qudc vd vung Ddng A, trong dd kieu gen C chiem da sd d ngudi nhilm VRVGB. [8]
Cdc trieu chiing thudng gap la: met mdi, chdn dn, mdt ngu ... chiem ty le cao hon d nhdm kilu gen C so vdi nhdm kilu gen B. Su khdc nhau d 2 nhdm kieu gen cd y nghia thdng ke (p < 0.05). Tuy nhien do doi tugng nghien ciiu d ddy Id nhirng benh nhdn den khdm vd dilu tri ngoai tni nen trieu chiing 1dm sdng khd ngheo ndn.
Ty le cdc ndng dp ALT d hai nhdm kieu gen B vd C tuong duong nhau. 40% nhdm kieu gen C cd nong dp ALT cao ban 5 lan GTBT so vdi 30,6% d nhdm kilu gen B.
Theo Sugauchi, ndng dp ALT, HBV DNA vd ty le HBeAg (+) d benh nhdn kieu gen C cao hon rd ret so vdi kilu gen B (p<0.05). Nhu vay theo tit cd cdc tdc gid, nhdm benh nhdn kieu gen C dudng nhu cd tinh trang viem-hoai tu te
bdo gan ndng nl hon so vdi nhdm bpnh nhdn kieu gen B.
4.2.Lien quan giira kieu gen cua HBV vdi HBeAg vd HBV DNA
Kilu gen C cd ty le HBeAg (+) cao hon so vdi nhdm kilu gen B (56% so vdi 38,8%, p <
0.05). Nhdm benh nhdn ciia Hodng Tiln Tuyen cd ty le HBeAg (+) tuong duomg: 39,4% d nhdm kilu gen B vd 63,9% d nhdm kilu gen C [4].
Nguyen H. Long vd cs d Hoa Ky cho biet ty le HBeAg (-) ciia tat cd benh nhan Id 64%
nhung khdng cho bilt ty le d timg nhdm kieu gen Id bao nhieu. Tuy nhien day la mdt ty le khd cao so vdi 2 nhdm kilu gen B vd C ciia chiing tdi (44% vd 61,2%). [4]
Ve su lien quan vdi nong dp HBV DNA, chiing tdi nhan thdy 67,4% benh nhdn kieu gen B vd 80% bpnh nhdn kilu gen C cd HBV DNA tdng cao ban 10' copies/ml (p>0.05). Ndng dp HBV DNA > 10' copies/mL d nhdm benh nhan kieu gen C cao horn nhdm kieu gen B (36% so vdi 28,6%, p > 0.05)
Theo Nguyen Cdng Long vd cs, ndng dp HBV-DNA cao cd lien quan den kieu gen C vd dien tien ndng d benh nhdn VGVRB man tinh.
Ndng dp HBV DNA d nhdm kieu gen C cao hon kieu gen B (6,6 ± 2,2 so vdi 4,9 ± 2,0 log copies/mL,p<0.0001) [3].
Yu vd cpng su d Ddi Loan theo ddi 4841 benh nhdn nam VGVRB man cho thdy kieu gen C cd lien quan vdi tang ndng dp HBV DNA huyet thanh. Cdc tdc gid McMahon, Chu vd A. Lok (Hoa Ky) ciing cd kit ludn nhu tren [4], [6]. Ndng dp HBV DNA tang cao d benh nhdn kieu gen C cd lien quan den nguy co tien triln nang cua benh VGVRB man d nhdm kilu gen ndy.
V . K i t luan
Kilu gen B chilm uu thl vdi 60,5% ; kilu gen C chi cd 30,9%; ddng nhilm B vd C chilm tyleit(8,6%).
Cdc trieu chiing met mdi, chdn an, mit ngu ... chilm ty le cao horn d nhdm kieu gen C so vdi nhdm kilu gen B. Benh nhdn kilu gen C
cd tinh trang viem-hoai tut te bdo gan nang hon so vdi nhdm benh nhdn kilu gen B.
Kieu gen C cd ty le HBeAg (+) cao ban vd cd the hen quan vdi tang ndng dp HBV DNA huylt thanh so vdi nhdm kilu gen B.
30 Tap chi GAN MAT VIET NAM so 16& 17-2011
Tai lieu tham khao
•
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Tran Xudn Chuotig (2009), Kieu gen cua vims viem gan B v^ y nghTa lam sAng, NXB Dai hpc Hue.
Nguyen Cdng Long, Bdi XuSn Trirdiig, Nguyin Khdnh Trach, Trin Minh Phvomg, Nguyen Trirong Son (2008),"N6ng dp HBV- DNA cao lien quan den kieu gen C vd b?nh gan nang d benh nhan Vi^t Nam nhiem vi-nit viem gan B man tinh", Tap chi Khoa hpc tieu hda Viet Nam, t§p 3,s6 1 l,tr. 669-673.
Hodng Tien Ttiyen (2011), "Nghien ciiu moi lien quan giira kieu gen, tdi lugng vi nit vdi cdc bieu hien lam sang nhiem vi nit viem gan B", 2.
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Tdm tdt Lu^n dn Tien sT Y hpc, Hpc vien Quan Y.
5. Chu C, Anna SF Lok (2002), "Clinical signif- icance of hepatitis B vims genotypes", Hepa- tology, 35, p. 1274-1276.
6. McMahon B J . (2009), 'The influence of hep- atitis B vims genotypes and subgenotypes on the natural history of chronic hepatitis B", Hepatol Int. 3: 334-342.
7. Nguyen LH, Ha NB, M H Nguyen et al (2009), "Prevalence of hepatitis B virus geno- type B in Vietnamese patients with chronic hep- atitis B", Hepatol Int. 3:461-467.
8. Yuen MF et al (2004), "Epidemiological study of hepatitis B vims genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong", Journal of Hepatol- ogy, 41, p.l 19-125.
