Nghien cihi moi lien quan giu-a kieu gen vol mot so trieu chung lam sang, can lam sang 6" benh nhan xo" gan do vi riit viem gan B
HOANG TIEN TUYEN *, NGUYEN VAN MIJI *, TRINH THI XUAN HOA*
Abstract:
Study on the 38 patients of cirrhosis causer by Hepatitis B virus. Our data showed geno- types B and C only. The rate of genotype C higher than genotype B (57,1% and 42,9%).
There was no relationship between HBV geno- type and feature clinic, Bilirubin total, AST,
Tom tat:
Nghien cuu 38 benh nhan xo gan do vi nit viem gan B gay ra. Ve kieu gen ciia vi nit viem gan B, chiing toi chi xac nhan dugc kieu gen B va C trong do kilu gen C ehiem ti le 57,1%,
9 F \ F
kieu gen B ehiem ti le 42,9%. Ve moi lien quan
t F t
giiia kieu gen B va C voi mot so bieu hien lam sang va xet nghiem, chiing toi nhan thay khong
1. Dat vin dl
F y. F >
Viem gan vi nit B la van de y te toan eau.
Voi khoang 2 ty nguoi nhiem vi nit viem gan B, trong s6 do co khoang 400 trieu nguoi nhilm man tinh. Khoang 1/4 so nguoi nhiem man tinh se tu vong do cac bien ehiing xo gan, HCC [4].
Hien nay, 8 kieu gen ciia vi nit viem gan B da dugc xac dinh va dugc ky hieu blng cac ky tu la tinh tiJ A-H. Kilu gen B va C la 2 kilu gen chii ylu 6 khu vuc Chau A - Thai Binh Duong. Vai tro cua kieu gen trong co che sinh benh cua HBV con chua dugc hieu biet mot each day dii [5].
Mot vai nghien cuu gdn day tren thi gidi 2. Do! twong va phirong phap nghien cmi 2.1. Bdi tiecmg. Tieu ehuan lira chpn benh nhdn nghien ciht.
Lua chon theo tieu ehuan cua Bruce
ALT, HBeAg viral load in cirrhosis patients genotype C and genotype B. The rate of cir- rhosis patients Child C genotype B higher than genotype C (p>0,05).
Key word: hepatitis B virus, cirrhosis
F \
CO moi lien quan ve lam sang, ham lugng Bilirubin TP, AST, ALT, HBeAg, tai lugng vi nit giiia benh nhan kieu gen B va C (p>0,05), CO moi lien quan ve tien lugng benh theo Child -Pugh, benh nhan xo gan kieu B nang hon kieu C (p<0,05)
Tir khoa: vi nit viem gan B, xo gan
cho rang ti le benh nhan xo gan kilu gen C eao hon kieu gen B. 6 nuoe ta, trong vai nam gkn day da co mot vai nghien cuu xac dinh kilu gen eua HBV o benh nhan xo gan. Nghien cuu moi lien quan giua kieu gen voi bilu hien lam
F F r
sang thi chua thay thay cong bo.
Chiing toi nghien cuu dl tai nay voi muc tieu:
Xac dinh kieu gen & benh nhdn xagan do vi rut viem gan B
- Xac dinh moi lien quan giiia cdc kieu gen tren mot so trieu chung lam sdng, can lam sdng.
R.Bacon {Harrison s nam 2009)
• Hgi chiing tang ap luc tinh mach cua - C6 truong tu do, dich thim
Benh vien Quan y 103.
- Lach to do u mau - Gian vong noi cua- chu
• Hoi ehiing suy ehuc nang gan: chan an, an khong tieu, dhy bung, dai tien phan tao long thit thuong, phu, xuit huylt, vang da, hoi chiing tang, giam duong mau, giam ham muon tinh due, sao mach (spider nevi), ban tay son (palmar erythema)... Xet nghiem: Protein mau giam, Albumin giam, A/G<1, ti le Prothrombin giam, AST, ALT tang trong dgt tien trien...
F
• Gan to, chac hoac gan teo
• hoac CO tien su xo gan mat bu
• HBsAg (+) > 6 thang hoac HBsAg (+), Anti HBc IgG(+)
hoac ton thuong mo hoc voi HAI xo = 4 diem
Tieu chudn loai trie
Loai trir nhiing benh nhan ra khoi nghien cuu khi CO nhung dae diem sau:
F
• Benh nhan c6 ket hgp cac nguyen nhan khac nhu: ton thuong gan do thuoc, do
hoa chat, do rugu, benh tu mien...
• Benh nhan nhilm kit hgp HCV, HFV...
• Benh nhan dang mac benh kit hgp nhu:
Sot ret, tieu duong, viem duong mat...
2.2. Phirffngphdp nghien cmi
Nghien ciiu tien ciiu, mo ta, cit ngang Tat ea cac benh nhan nghien ciiu dugc khao sat theo cac thong so sau:
• Cac trieu chiing lam sang
• Cac xet nghiem AST, ALT, BilirubinTP, cac thong so huyet hoc
• Marker HBV
• Dinh lugng HBV bing ky thuat realtime PCR tren may Realtune - PCR LightCycler 2.0 eua hang Roche Thuy Si
• Xac dinh kieu gen cua HBV bang ky thuat PCR- RFLP {Polymerase Chaine Reaction - Restriction Fragment Length Polymorphisme)
Cac ky thuat dugc thue hien tai Labo Sinh hgc phan tu, true thuoc Trung tam nghien cuu ung dung Sinh - Y- Dugc hoc, Hoc vien Quan y
F
Xielysolieu
Cae ket qua dugc su ly bang phan mem SPSS vaEPI-INFO 6.0
3. Ket qua
Bang 3.1: Phdn bo kieu gen a benh nhdn xagan
42,1%
DHBV-B
• HBV-C
22(57,9%)
Ti le benh nhan xo gan kilu gen C cao hon kilu gen B (57,9% so voi 42,1%). Kilu gen A,D,E,F,G,H khong thiy xuit hien trong nghien ciiu nay
Bdng3.2: So sanh mot so trieu chung lam sdng giiia benh nhdn xagan kieu gen BvdC ICieu gen
Trieu chiing
s6t
Met
Roi loan giic ngu Roi loan tieu hoa Dau ha sudn phai Vang da
Nuoe tilu vang Gan to
Lach to Phu
/ F
Xuat huyet Sao mach
Tuan hoan bang he
Tri
KieugenB(n=16) n(%) 6(37,5) 16(100,0)
13(81,3) 11(68,8) 7(43,7) 16(100,0) 16(100,0) 15(93,8)
6(37,5) 8(50,0) 11(68,8)
8(50,0) 5(31,3) 2(12,5)
Kieu genC (n=22) n(%)
7(31,8) 22(100,0)
19(84,6) 16(72,7) 14(45,0) 17(77,3) 20(90,9) 18(82,8) 12(54,5) 11(50,0) 10(45,5) 11(50,0) 10(45,5) 2(6,2)
P
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05
Phu, xuat huyet, tuan hoan bang he, lach to gap voi ti le kha eao 6 benh nhan xo gan. Tan suat xuat hien trieu chiing giiia benh nhan kieu gen B va C khong c6 su khac biet thong ke (p> 0,05)
Bdng 3.3: So sanh hoat do enzyme AST, ALTvd hdm luang Bilirubin TP giita benh nhdn xa gan kieu gen BvdC
^"~~-~^,.,^ Kieu gen Chi tieu ^"""'•"---^^
BilirubinTP (XdbSD i^mol/l) AST(X±SDU/1) ALT(X±SDU/1)
KieugenB(n=16) n(%)
166,2 ±139 211,8± 119,1 238,4 ±235,5
Kieu genC (n=22) n(%)
95,1 ± 142,1 196,4 ±115,9 173,8 ±175,3
P
>0,05
>0,05
>0,05
Hoat do enzyme AST, ALT va ham lugng Bilirubin TP o benh nhan xo gan kilu gen B eao hon benh nhan kilu gen C nhung khong co su khac biet c6 y nghia thong ke (p>0,05)
Benh nhan xo gan kieu gen C co ti le HC giam cao hon benh nhan xo gan kilu gen B (81,8% so voi 50,0%)v6i su khac biet co y nghia thing ke voi p<0,05.
Bdng 3.4: Tdi luang vi rut vd HBeAg giiia benh nhdn xa gan kiiu gen BvdC
• Kieu gen Chi tieu "^ ~~—____
HBV-DNA (copies/ml) . HBeAg(+)
HBeAg(-)
KilugenB(n=16) n=16
2,05x106± 4,22x106 3(18,8) 13(81,2)
Kieu genC (n=22) n=22
2,51xl06±5,85xl0«
6(27,7) 16(72,3)
P
>0,05
>0,05 Tai lugng vi nit, ti le HBeAg(+) 6 benh nhan xo gan kieu gen C cao hon kieu gen B nhung su khac biet khong eo y nghia thing ke (p>0,05)
Bdng 3.5:Phdn bo mire do benh theo Child score giiia benh nhdn xa gan kieu BvdC
^ •—-______^ Kieu gen
Child-Pugh seore^ -~-____^^
5-6 (Child A) 7-9 (Child B) 10-15 (Child C)
KieugenB(n=16) n(%)
1 (6,3) 5(31,3) 10(62,4)
Kieu genC (n=22) n(%)
8(36,4) 8(36,4) 6 (27,2)
P
>0,05
>0,05
<0,05
/ •> •> F
So lugng benh nhan xo gan Child C o kieu gen B cao hon kieu gen C co y nghia thong ke voi p< 0,05.
4. Ban luan
•
Khu vuc chau A - Thai Binh Duong la khu vuc ma hau het nguoi nhilm vi nit viem gan B kilu gen B va kilu gen C Nghien cuu vl phan bo kieu gen 6 benh nhan xo gan dlu eho thiy ti le benh nhan co kieu gen C eao hon kilu gen B, nhung ti le khac nhau 6 timg nude [6]. o Trung Quoc, nghien ciiu cua Ding X cho thiy 91,4% benh nhan xo gan c6 kilu gen C trong khi do chi c6 8,6% benh nhan eo kilu gen B [3], o Hong Kong, kit qua nghien ciiu ciia Lai W la 72,73% va 27,27% [5],d Nhat Ban, kit qua nghien ciiu cua Orito E la 50% va 50% [7].
o nuoe ta, nghien ciiu cua cua Nguyen Truong Son tai Ha Noi eho thiy benh nhan kilu gen C la 56,8%, benh nhan kilu gen B la 43,2%[2].
Ket qua nghien ciiu ciia ehiing toi cho thiy, trong s6 38 benh nhan xo gan xac dinh dugc kilu gen, kilu gen B la 42,1%, kilu gen C la 57,9%.
Xo gan la dich cuoi cung cua qua trinh viem man tinh. Do vay, benh canh lam sang ciia xo gan thue chit eiing khong c6 gi khac biet voi benh canh lam sang cua viem gan man. Mai
Hong Bang va cong su nghien ciiu tren 170 benh nhan eho thay: sot nhe c6 o 41,1%, met moi :94,7%, ngu kem: 91,2%, chan an: 89,4%, dai tien phan long: 31,6%, phu: 17,6%, sao mach :4,1%, vang da: 94,1%, tuin hoan bang he :37%, gan to: 82%, lach to: 14,1% [1].
Nghien ciiu eua ehiing toi tren 38 benh nhan xo gan trong do 8 benh nhan dugc chin doan qua hinh anh mo benh, 30 benh nhan dugc chan doan theo lam sang da eho kit qua tuong tu. Tim hieu su khac biet v l tin suit xuit hien cua cac trieu chmig tren 6 hai nhom benh nhan xo gan CO kilu gen B va kilu gen C, kit qua eho thay tan xuat xuat hien ciia cac trieu chiing lam sang tren o ca 2 nhom benh nhan hoan toan tuong duong. Nghien ciiu ham lugng trung binh Bilirubin TP, hoat do trung binh AST, ALT chung toi nhan thiy o benh nhan kieu gen B cao hon kilu gen C nhung su khac biet khong eo y nghia thong ke voi p > 0,05 (166,2 ± 139 mol/l; 211,8± 119,1U/1 U/l ; 238,4± 235,5 so v&i 95,1± 142,Imol/l; 196,4 ± 175,9UA; 173,9 ± 175,3U/l). Nghien cuu cua
Tangkijvanich P tai Thai Lan tren 54 benh nhan trong do 10 benh nhan kilu gen B, 44 benh nhan kilu gen C cho thiy ham lugng trung binh Bilirubin TP, hoat do trung binh ALT o nhom benh nhan kilu gen C cao hon kilu gen B nhung su khac biet nay khong eo y nghia thing ke [8]. Tim hilu mli lien quan giua kilu gen B, C voi marker HBeAg(+) va tai lugng vi rut o benh nhan xo gan. Ding X nhan thiy co 12/35 benh nhan nghien ciiu eo HBeAg(+) va 100%) s6 benh nhan eo HBeAg(+) nay thuoc nhom benh nhan co kieu gen C [3]. Ket qua nghien ciiu eua Tangkijvanich P la 1/9 benh nhan kieu gen B, 25/44 benh nhan kieu gen C,
t F
tai lugng trung binh vi nit 6 kieu gen B thap hon kilu gen C (6,59logl0 so voi 7,05 log 10).
F
Nghien ciiu cua chiing toi cho thay chi co 9/38 benh nhan co HBeAg(+) va ti le benh nhan eo HBeAg(+), tai lugng vi nit trung binh o benh nhan xo gan kieu gen B thap hon nhom benh nhan kieu gen C (18.8% so v&i 27.3%; 2,05x 10^± 4,22 xlO^ copies/ml so v&i 2,51x 10^
±5,85x10^ copies/ml) . Su khac biet nay khong
CO y nghia thing ke voi p > 0,05 [8]. He thong dilm Child-Pugh danh gia tien lugng xo gan bang each cho diem : Child A (5 - 6 diem).
Child B (7-9 diem). Child C (10-15 diem).
Trong 38 benh nhan ehiing toi xac dinh dugc 9 benh nhan Chidl A, 13 benh nhan Chidl B, 16 benh nhan Chidl C. Tim hieu su phan bo benh nhan theo miic do nang giua hai nhom benh nhan kieu gen B va kieu gen C, chiing toi nhan thay c6 su Idiae biet 6 nh6m benh nhan miic do nhe (Child A) va miic do nang (Child C). a nh6m benh nhan kieu gen B, Child C ehiem ti le eao so voi Child A (62,5% [10/16] so voi 6,3%) [1/16]), thi ngugc lai nhom benh nhan kilu gen C la Child A cao hon Chidl C (36,3%
[8/22] so v&i 27,2%[6/22]). Su khac biet nay
F
CO y nghia thong ke voi p < 0,05. Nghien ciiu eua Tangkijvanich tai Thai Lan hoan toan cho ket qua khac biet voi chiing toi, o nhom benh nhan kilu gen B, Child A la 70% (7/10), Child C la 10% (1/10), 6 nhom benh nhan kieu gen C tuong tu lin luot la 54,5% (24/44), 11,3%
(5/44)m.
5. Ket luan
Tii ket qua nghien ciiu 38 benh nhan xo gan do vi nit viem gan B gay ra, chiing toi nit ra
F F
mot so ket luan sau:
9 9 r
- Kieu gen B va C la 2 kieu gen duy nhat dugc xac dinh trong nghien ciiu nay voi ti le kilu gen C chilm 57,1%), kieu gen B ehiem 42,9%
- Khong CO moi lien quan giua cae trieu chiing lam sang, ham lugng BilirubinTP, AST, ALT, HBeAg, tai lugng vi nit giCra benh nhan kilu gen B va C (p>0,05)
- Benh nhan xo gan kieu gen B tien lugng benh theo Child -Pugh nang hon kieu gen C (P<0,05).
Tai lieu tham khao
1. Mai Hdng Bang, Vii Thanh Trung (2006), "Dae diem lam sang, can lam sang cua benh viem mang bung nhiem khuan tu phat o benh nhan xo gan". Tap chi Y hoc, chuyen dl gan mat, tap 329, tr .122-
128
2. Nguyen Truong Son, Bui Xuan Truomg va cong su (2008), "Nghien cihi ti le cac kilu gen cua vi nit viem gan B tai miln Bic Viet Nam", Tap chi khoa hoc tieu hod, so dae biet, tr .862
3. Ding X., Mizokami M. et al. (2001),
"Hepatitis B virus genotype distribution among chronic hepatitis B virus carrier in Shanghai, China", J of intervirology,44, pp.43-47
4. Lavanchy D. (2005), "Woldwide epi- demiology of HBV infection, diseases burden, and vaccine prevention", J of clinical virology, 34 supp.l l,pp,l-3 5. Lai W. (2009), '"HBeAg negative hepatitis
B and relationship to genotyping"
http://www7.nationalacademies.org/GDE ST- China
7.
Mizokami M. (2007), "Global distribu- tion of HBV genotypes- implication on clinical manifestations and disease burden",
Orito E., Ichida T., Sakugawa H. et al.
(2001), "Geographic distribution of hepa- titis B virus (HBV) genotype in patient
with chronic HBV infection in Japan", Hepatology 34(3), pp.590-594
8. Tangkijivanich P. et al. (2005), "Hepatitis B virus genotpe and hepatocellular carci- noma in Thailand", Word J Gastroenterol,
11(15), pp2238-2243.
