Tap chi GAN MAT VIET NAM so 24-2013
Mot so dac diem lam sang va can lam sang cua ung thu* bieu mo tl bao gan (HCC) lien quan vol HBV 6* phia nam Viet Nam*
Some clinical and laboratory characteristics of HBV related HCC in the southern of Vietnam
PHAM HOANG P H I E T ' \ D 6 DINH CONG', TRUONG BA TRUNG'-^
DONG THI HOAI A N ' ' ^ NGUYEN CHI VINH', Lfi THJ THANH'
A b s t r a c t
Background. HCC became the most common cancer with the highest rate of cancer related mortality in Viet nam.Around 70 to 90% of this HCC having HBsAg positive. This study aims at investigating some clinical and laboratory characteristics of HBV related HCC patients living in southern Viet nam.
Patients and methods. This is a prospective and non interventional study. Patients were recruited at HCMC University Medical center from 2010 to 2011 with inclusion criteria was confirmed HCC with HBsAg positivity.Labo- ratory tests consist of biochemistry,hemato- logic, liver function tests and virologic tests (qHBsAg,HBeAg, viral load.HBV genotyp- ing,double BCP mutation).
Results and discussion. A total of 130 patients were recruited.Men/women ratio = 9/1. The rate of ASZALT. GGT higher than ULN are 65.2%; 65,2% and 91,3% respec-
tively. Child Pugh class A= 88,6% and class B
= 11,4%. The AFP levels: 24,8% below 20ng/ml and 30.4% above 400ng/ml. The HBV load > 10^ cps/ml presents in 60% of patients.
And 40% of patients with viral load <10^
cps/ml having qHBsAg > 1 OOOiu/ml. The rate of HBeAg positive, HBV genotype B+C / C as well as double BCP mutation in the HBV related HCC patients were statistically higher than those of the historical chronic hepatitis B without HCC in control group.
Conclusion. In this study the men/women ratio was very high.The PPV as well as NPV values of AFP in the diagnosis of HCC were low. The majority ofHB V in HB V related HCC patients was still in active state and all studied criteria of HCC risk factors such as HBeAg positivity, HBV genotype C.double BCP muta- tion were statistically higher than the control CHB group.
T o m t a t .
HCC hien da tro thanh loai ung thu dung hang dSu v^ xuit do va tut xuat ung thu a Viet nam.Khoang 70% dSn 90% HCC 6 Viet nam CO lien quan voi HBV bai vay nghien cuu nay nham gop phan lam sang to them mot so dac di^m lam sang va can lam sang cua loai ung thu nay.
Benh nhan vd phw<mg phdp: Day la mpt nghien cihi tiin cum khong can thiep.Benh nhan dugc chgn tu Benh vien DH YD Tp HCM trong 2 nam 2010 va 2011 vol tieu chuSn la chdn doan xac dinh HCC voi HBsAg duong
tinh. Cac xet nghiem bao gom chiic nang gan dong mau va cac dau an mien dich va sinh hpc phan tu cua HBV.
Ket qud vd bdn luan: Tong so 130 benh nhan,ty le nam/nii ^ 9/1. Cac men gan AST/ALT/GGT cao tren muc binh thuong vai ty le la 65,2%;65,2% va 91,3%. X8p loai xo gan theo Child Pugh thi lop A la 88,6% va lop B la 11,4%. Dinh lugng AFP huySt thanh co 34,8% thdp <20ng/ml va chi co 30,4% cao
>400ng/ml. Nhiing dac diSm HBV co lien quan voi nguy co HCC bao gom HBVDNA
*La mpt phdn DS tai cdp thanh ph6,Ca quan quan ly: Sa khoa hpc cong nghe Tp HCM.
'Benh vi6n Dai hpc Y Duac Tp HCM, ^Phong kham Gan Mat Sai Gon.
Phan bi6n Idioa hpc; GS f s Vu B5ng Dmh.
Tap chi GAN MAT VIET NAM s6 24-2012
cao >10'''^''Vml chiSm 60% va 40% benh nhan CO HBVDNA thap <10^^i"'/ml co qHBsAg
>1 OOOiu/ml. So nhom b?nh nhan HCC vdi nhom chung lich su thi ty le c6 HBeAg duong tinh la 32,1% vs 20,9% (0R= 1,786; 95%
Cl:l,0047 3,1876); ty Ip cac ki6u gen B/B+C/C cung CO si; khac biet ve tang typ gen B+C va C vcri X ^ =22,1 va p<0,000 ; dot bien
kep BCP ty le la 57,4% vs 24,5% (OR=3,383;
95% CI: 1,8875-6,0636).
Ket lu^n: HCC lien quan vai HBV co ty le nam gioi rdt cao so vai nii giai.Gia trj chan doan va loai trir cua AFP rat han che.Cac dac di^m ve virus hgc cho thay HBV a bpnh nhan HCC CO ty Ip dang hoat tac va co cac chi ddu nguy CO tien doan HCC cao.
1. Mb* dau.
Ung thu gan nguyen phat (UTGNP) la mgt loai ung thu ph6 biln tren toan cau va co ty le tu vong cao. Theo so lieu tu Globocan 2008,tren toan thi gidi UTGNP c6 xudt dp dung thii 5 trong cac loai ung thu pho bien nhat va dung hang thu 3 trong cac ung thu co so lugng hi vong cao nhat.
Khoang 85% truong hgp UTGNP xudt hien trong cac nuac dang phat trien va ty le nam/nu chung vao khoang 2 den 4 lan. Uoc tinh cua nam 2008, toan th8 gidi c6 748.300 trudng hgp UTGNP va 694.000 trudng hgp tii vong {ty sudt tu vong/trudng hop mdi khoang 0,93)(1).
Khu vuc Dong va Dong nam A bao gom ca Viet nam la vung cd UTG NP cao so vdi the gidi va ddng thdi ciing la khu vuc dich te hpc nhiem cao cua virus viem gan B (HBV)(2).
Ung thu bieu md te bao gan (HCC^Hepato- cellular carcinoma) la the md hpc phd bien nhat cua UTGNP. Theo El Sarag HB va cs, tren toan cau HCC chiem khoang 85 den 90%
UTGNP vi vay nhieu tac gia da six dung tu HCC thay cho UTGNP ndi chung. Trong bao cao nay chung tdi cung sii dung tii HCC chung 2. Benh nhan va phirtmg phap.
Day la mpt nghien ciiu quan sat lam sang tien ciiu va khdng can thiep vao quy trinh dicu tri cua benh nhan tai co sd dieu tri.
Benh nhan dugc chgn tai Benh vien Dai hgc Y Dugc Tp HCM vdi cac tieu chudn bao gdm:
Dugc chan doan la HCC dua vao hinh anh khdi u vdi dac diem dien hinh cua bdt thudc can quang: Tang trong thi dgng mach va tdy sach trong thi tinh mach/thi cham tren CT hay MRI hoac khoi u dien hinh tren hinh anh kem vdiAFP>400ng/ml.
Tieu chuan cua HC" lien quan vdi HBV la
cho UTGNP d Vipt nam.
Theo sd lipu cua GLOBOCAN 2008, HCC d Viet nam da trd thanh loai ung thu phd biin nhdt d ca nam va nir va dong thdi cung xep hang cao nhdt trong tu vong v^ ung thu. Cy the sd lieu cua Viet nam 2008 thi HCC cd xudt dp mdi hang nam theo tudi chuan cua ca 2 gidi (ASIR) cua Viet nam la 29,3/100.000 va tu sudt hang nam (ASMR) la 27,3/100.000. NSu tinh theo gidi thi ASIR va ASMR d nam gidi la 42,3 va 39,2/100.000 va tuong ling cho nii gidi la 18,5 va 17,3/100.000 (I). Tii vong hang nam do HCC d Vipt nam udc tinh khoang 21.748 gdn gdp 2 ldn sd lugng tu vong do tai nan giao thdng. Theo thdng ke ciia Uy ban an toan giao thdng qudc gia nam 2011 ca nude co 44.540 vu tai nan giao thdng lam 11.395 ngudi tu vong (3). Cho den nay, chung ta van chua cd mdt chuang trinh tam soat cQng nhu nghien ciiu chung ve HCC thich hgp va hieu qua trong hoan canh cu the ciia Viet nam. Nghien cuu nay nham muc dich gdp phan lam rd hon mot sd diem ve lam sang va can lam sang cua HCC lien quan vdi HBV.
benh nhan chan doan la HCC kem vdi HBsAg duong tinh va khong cd ddng nhiem vdi HCV,HIV.Ngoai ra benh nhan cdn dam bao de cho phep cd chi dinh dieu tri can thiep (phau thuat hay can thiep tai cho RFA,TACE,TOCE w . . ).
Cac xet nghiem sinh hda dugc tien hanh tren may sinh hda tu ddng Olympus 648
Cdng thirc mau thirc hien tren may dem tu ddng Cell Dyn 3700 cua hang Abbott
Xet nghiem ddng mau thuc hien tren may ddng mau Stargo
Tap chi GAN MAT VIET NAM so 24-2013
Dinh tinh vk dinh lugng HBsAg thuc hien tren mSy Architech Ci 8000 cua hang Abbott.
Dinh lupng HBV DNA dita tren ky thuat Real time PCR vcri Taqman probe.
Dinh typ gen HBV b k g ky thuat Multiplex.
3 . Ket qua nghien ciru:
Dac diSm lam sang va xet nghiem cua HCC lien quan vai HBV trong nghien cuu nay.
3.hD^c diem ve dan s6 hpc trong nhom duyc nghien cuu.
Tdng s8 b$nh nhan: 130
Giai: nam 117 v4 nu 13;Ty le nam/nu : 9/1 Phan bo benh nhan theo nhom m6i:
Nh6m < 40 tudi 13(10%) 4 0 - 4 9 30(23,1%) 50 - 59 47 (36,2%) 6 0 - 6 9 30(23,1%)
> 7 0 10(7,7%) Giai han tu6i: Toi thieu la 31 tu6i va t6i da la 76.
Tu6i trung binh 53,72±10,74 Tuoi trung binh a: Nam giai: 53,63±10,90;
Nii giai: 54,20±23,0
Khong CO su khac biet ve tuoi giira 2 giai (p=0,9997).
3.2.Bac diem ve xet nghiem mien dich vd chirc nang gan.
Xet nghiem AFP: Tong so mau thii co ket qua la 92.
Luang AFP tinh theo ng/ml huyet thanh
< 2 0 n g 32(34,8%) T u 2 0 d S n < 1 0 0 n g 19(19,6%) Tir 100 dSn <200ng 6 (6,5%) Tvr 200 d6n <400ng 8 (8,6%)
> 400ng 28 (30,4%) N^u tinh gop, s6 benh nhan co AFP
>200ng/ml la 36/92 (39,1%) va s6 benh nhan CO AFP >400ng/ml la 28/92 (30,4%).
Xet nghiem Bilirubin toan phiin: T6ng s6 mSu thii 1^ 94.
<lmg/dl 70/94 (74,5%) Tir 1 dSn <2mg/dl 22/94 (23,4%) Tir2d6n<3mg/dl 2/94(2,1%)
> 3mg/dl 0/94_
Chi s6 dong mau INR: T6ng so mlu Ihu la 96.
C h i s 6 < l , 2 64/96(66,7%) l , 2 d S n < l , 7 30/96(31,3%)
Phat hien dot bien BCP bang ky thuat PCR- RFLP.
Cac so heu dugc tap hgp va xu ly theo phuang phap thong ke sinh hpc.
>1,7 2/96(2,1%) Albumine huyet tuang (g/dl): Tong so m l u
thu 96.
>3,5g/dl 74/96(77,1%) Tir 3,5 ddn 2,8g/dl 20/96 (20.8%)
<2,8g/dl 2/96(2,1%) Co dich 6 bung: Tong so c6 ket qua 88.
Khong CO dich 6 bung 76/88 (86,4%)
Co It dich 8/88(9,1%) Co dich trung binh 4/88(4,5%) Khong CO trudng hgp nao cd bieu hien rdi loan nao gan.
Tap hgp 5 chi tieu Bilirubin toan phln,INR, Albimiin,dich d bung va dau hieu nao gan thi benh nhan c6 diem Child-Pugh nhu sau:
5 didm 61/88 (69,3%) 6 diSm 17/88 (19,3%) 7 dilm 6/88 (6,8%) 8 dilm 4/88 (4,5%) Phan loai xa gan: Child-Pugh A la 78/88 (88,6%) va Child-Pugh B la 10/88 (11,4%).
Thay ddi ve men gan:
AST tdng sd 92
<30u/l 8/92 (8,7%) 30 d i n <40u/l 24/92 (26,1 %) 40 din <60u/l 22/92 (23,9%) 60 din <80u/l 22/92 (23,9%)
>80u/I 16/92 (17,4%) ALT tdng sd 92
<30u/l 28/92 (30,4%)
3 0 d l n < 4 0 u / l 18/92(19,6%) 40 den <60u/l 20/92 (21,7%)
6 0 d l n < 8 0 u / l 12/92(13,0%)
>80u/l 14/92 (15,2%) Ty le benh nhan co AST/ALT > 1 la 60/92 (65,2%).
GGT tong sd 92
<40u/l 8/92 (8,7%) T u 4 0 d l n < 8 0 u / 1 16/92(17,4%) Tii 80 din <200u/l 44/92 (47,8%) c6 2 benh nhan nG
8 T9pchiOANMATVIETNAMs624-2012
>200u/l 24/92 (26,1%) khdng c6 b?nh nhan nii.
Tdng hgp lai ta cd > 9 1 % b?nh nhan (84/92) men GGT cao hon binh thuemg ma chii ylu Ik nam gidi (ty 1? nam / nu la 64/4 = 16!) nhat la hong nhdm cd GGT cao tren 2 lin gidi han tren cua binh thudng.
3.3.Bfc diem virus hoc: dau an huyil thanh va sinh hQcphan tuciia HCC tien quan v/H HBV.
3.3.1.Bgc diim ddu an huyet thanh hqc.
Dinh lugng HBsAg.Tit ca benh nhan deu dugc xet nghi?m HBsAg duong tinh bing ky thuat dinh tinh hay dinh lugng chieu theo tieu chuin lira chgn b^nh nhan. 6 day chiing tdi chi phan tich 86 trudng hgp dinh lugng HBsAg tinh bang iu/ml.
HBsAg < 1 OOiu/ml 12/86(14,0%) 100 din < lOOOiu/ml 14/86 (16,3%) 1000 din <10.00Diu/ml 54/86 (62,8%)
>10.000iu/ml 6/86(7,0%) Khang nguyen HBeAg: Tdng sd 81 trudng hgp.
HBeAg dugng tinh 26/81 (32,1%) HBeAg am tinh 55/81 (67,9%) Nhdm benh nhan HCC cd HBeAg am tinh cd tudi trung binh cao benh nhan cd HBeAg duong tinh khoang 6 tudi nhung su khac biet nay chua cd y nghia thdng ke (55,89±10,62 vs 49,35±10,25; p>0,05).
3.3.2. Bgc diem sinh hoc phdn tu cita HBV trong HCC.
3.3.2.1. Tai lugng virus qua dinh lugng HBVDNA tinh bang ban sao (copies:cps)/ml tinh quy ddi thanh don vi quoc te lU theo: 1 lU
= 5cps.Dd nhay ky thuat vao khoang 300 - 500cps/ml.
H B V D N A a m t i n h 14/130(10,8%) Duong tinh <3 log 10 13/130(10,0%) 31ogdln<41og 25/130(19,2%) 4 1 o g d l n < 5 1 o g 17/130(13,1%) 5 log d i n <6 log 26/130(20,0%)
6 log d i n <7 log 18/130(13,8%) 7 log din <8 log 13/130(10,0%)
> 8 1 o g 4/130(3,1%) Nhu vay benh nhan cd HBV DNA ducmg
tinh (>30()-500cps/ml) chilm 116/130(89,2%) B?nh nhan cd HBV DNA >3 log cps/ml la 103/130(79,2%)
Benh nhan cd HBV DNA >4 log cps/ml la 78/130(60,0%)
Lien quan giiia djnh lugng HBV DNA va tinh trang HBeAg.
Tren 26 b$nh nhan cd HBV DNA cao >4 log cps/ml thi cd 21/25 (84,0%) la cd HBeAg duong tinh va hen 55 b?nh nhan cd lugng HBV DNA thip <4 log cps/ml chi cd 28/55 (50,9%) cd HBeAg dugng tinh.Su khac biet nay la cd y nghia thdng ke ( 0 R = 4,36 vdi 95% C I : 1,44 - 13,21;
p<0,02).Nhu vay, nhiing benh nhan cd HBV DNA cao thudng ciing cd HBeAg ducmg tinh.
3.3.2.2. Typ gen cua HBV (HBV GT) tren benh nhan HCC. Ky thuat xac dinh HBV GT va ca dot biln loi (BCP) ciia chimg tdi chi xac dinh dugc khi lugng HBV DNA khoang tir >3 d i n 4 log cps/nd.
Tdng sd benh nhan cd ket qua ve Typ gen HBV la 80 va phan bd cac typ nhu sau:
H B V G T B 44/80(53,2%) B-l-C 13/80(16,9%) C 23/80(29,9%) Tudi trung binh ciia benh nhan cd cac kieu gen B so vdi B+C va C cd xu hudng tang din tir 52,47±10,43 len 53,72±8,91 rdi len 55,52±10,56 song su khac biet nay ciing khdng cd y nghia ve mat thdng ke (p>0,05).
3.3.2.3. Dgt biln kep A1762T/G1764A.
Tdng sd benh nhan cd ket qua ve dot bien vimg loi (BCP) la 54.
Khdng dgt bien
(thi hoang dai) 23/54(42,6%) Cd dgt biln BCP 31/54(57,4%) Dot biln BCP theo HBV GTdugc trinh bay trong bang 2:
Bdng I: Dot bien BCP theo logi typ gen.
HBVGT Dot biln BCP Khong dot bien Co dot bien
HBVGTB 14 13
HBVGT B+C 5 7
HBVGTC 4 11
Tap chi GAN MAT VIET NAM so 24-2013
Ty Ip dot biSn kep d BCP tang dhn tii HBV GT B la 13/27 (48,1%) rdi tdi HBV GT phdi hgp B+C la 7/12 (58,3%) va cao nhit la HBV GT C la 11/15 (73,3%). Tuy nhien vdi sd m^u tuang doi nhd cua chiing tdi, sir khac biet nay chua cd y nghia vk thdng ke (p= 0,286).
Tudi cua benh nhan giua nhdm cd dot biSn kep d BCP va khdng cd dot bi6n:
4. Ban luan
Nghien ciiu nay dugc thuc hien tai benh vien Dai hgc Y dugc Thanh phd Hd chi Minh (BVDH YD TpHCM) ddi tugng nghien ciiu da dugc lira chgn trong cac bpnh nhan HCC dugc chan doan do mgi nguyen nhan va giai doan cua benh. Hai tieu chuan lua chgn chinh chung tdi mudn ban luan nay bao gdm:
Thii nhat la chi nhiing benh nhan HCC cd HBsAg duang tinh va
Thii hai la cd chi dinh can thiep di^u trj.
Khi chgn tieu chuan bpnh nhan dugc x8p la HCC lien quan vdi HBV chung tdi lay tieu chuan la phai cd HBsAg duong tinh va khdng cd ddng nhilm. Tieu chuan nay lam cho nhdm benh nhan dugc lira chgn de dang va khdng cd trudng hgp sai lam trong dieu kien thuc te Viet nam. Tuy nhien su lira chgn nay co the bd ra ngoai mgt sd benh nhan HCC lien quan vdi HBV th6 i n (Occult hepatitis B). G i n day, Wong DK va cdng su khi nghien ciiu tren 33 benh nhan dugc xep la HCC khdng rd nguyen nhan (cryptogenic HCC) da rihan thay 24/33(73%) la cd nhiem HBV thS i n qua xac minh cd HBVDNA,cccDNA,pgRNA trong td chiic gan va /hoac td chiic ung thu cua benh nhan (4). Kwon va cs cung nhan thay tren nhdm 72 benh nhan nam xo gan do rugu neu cd anti HBc lam tang nguy co HCC cd y nghia vdi 0 R = 3 , 1 ; 9 5 % Cl:l,354 - 7,098, p-0,007 (5).Nghien ciiu gdp cua Shi Y. va Cs phan tich tren 16 cdng trinh da cdng bd cho thay viem gan B t h i i n la nguy co lam tang HCC tu OR=2,86, (95% CI: 1,59-4,13) trong tap hgp 8 nghien ciiu tikn cuu va OR=6,08; (95%
CI:3,45 - 10,72) trong tap hgp 8 nghien cuu hoi ciiu (6).
Vi chi chpn cac benh nhan cdn cd chi dinh can thiep dilu tri nen benh nhan cua chiing tdi
Tudi d nhdm cd dot bien: 51,15±9,72 Tudi d nhdm khdng dot bien 54,17± 10,62 Nhan xet: nhdm tudi d benh nhan HCC cd dot bien kep BCP lai thap han nhdm khdng cd dot bien,tuy nhien sy khac bipt nay chua cd y nghia thong ke (p>0,05).
khdng bao gdm cac benh nhan d giai doan rat mupn nhu da cd di can, xo gan mat bu,rdi loan nao gan vv... so vdi nhijng nghien cuu trudc day. Dieu nay cung khdng ndi len la chan doan HCC d Viet nam hien nay da co tien bd ro ret va da phat hien benh sdm hon!
Trong nghien ciiu nay, ty le benh nhan nam/nir la cao 9/1. So vdi nhimg ket qua cdng bd trudc day ma chiing toi dugc biet ty le nay la cao vdi sd lieu cua the gidi va ca trong nude.
Tren the gidi tinh chung ty le benh nhan HCC d nam gidi so vdi nii gidi la tii 2 den 4 lan va d viing dich te hpc cd ty le HCC lien quan vdi nhiem HBV thi ty le nay tuong ddi cao hon.
Nhiing ket qua nghien ciiu trudc day d Viet nam dugc cdng bo tren y van thi ty le nam/nii deu thap hem so vdi so lieu trong nghien ciiu nay cua chiing tdi. Phiet va cs (1978) tren 404 benh nhan cd ty le nam/nii la 3,3/1 (7);
Tr.v.Huy (2003) tren 100 benh nhan ty le nay la 4,5/1 (8); Tr.v.Hgp va cs (2000) tren 562 benh nhan cho ty le la 5,2/1 (9); V.v.Vu va cs (2010) tren 107 benh nhan cho ty le nam/ nii la 3,8/1 (lO).Ty le nam cao hon nii ciia HCC lien quan vdi HBV la mgt nhan xet lam sang cd tii lau nhung gan day da cd nhiing nghien ciiu cho thay vai trd cua ndi td Androgen trong tang boat dgng cua HBV cung nhu tinh sinh ung.Tian Y va cs thyc nghipm tren chupt nhat chuyen gen mang toan bd genome cua HBV cho thay Androgen va Androgen receptor hoat dpng cd the lam tang sy nhan len cua HBV khoang 2 lan.Tac dung nay khdng cdn neu chupt dugc thien va phuc hdi neu tiem chat cd hoat tinh Androgen thay the(ll). Wang SH va cs (12) da xac dinh dugc 2 yeu td dap ling Androgen (androgen response element ) cd trong cau tnic ciia HBVDNA cd kha nang thiic
T9P chi GAN MAT VIET NAM so 24-2012
diy sao chep cua HBVRNA thdng qua sy lien kk vdi thu tbS Androgen (AR).Wu MH va cs (13) cung tren chupt chuyen gen vai trd cua tang biiu Ip AR lam tang sinh HBV v^ tang sao chep HBVRNA thdng qua sy gan kit tryc tiep ciia yeu td dap ling Androgen cua HBV. Hoat dgng nay la mpt cung phan hdi duong tinh (positive feedback mechanism) va ddng thdi phoi hgp vdi boat hda gen HBx protein lam thuc day tinh sinh ung. Tren nghien ciiu lam sang doan he ciia MW Yu va cs tap hgp mau mau ciia 4841 nam gidi ngudi Dai loan cd HBsAg+ va theo doi trung binh trong 12 nam cd xuat hien 119 HCC. Tac gia nhan thiy nhiing benh nhan cd Androgen cao va cac gen boat tac androgen (SRD5A2) va gen AR deu lam tang nguy co mac HCC cd y nghia thdng ke theo thii ty cua do chenh (OR) la 2,97(95%CI-1,54-5,70); 2,47(95%CI=1,21 - 5,03) va 1,64 (95%CI-1,00-2,68)(14). Nhung nghien ciiu tren day da gdp phan giai thich vi sao trong viem gan virus B d giai doan mudn la xo gan va nhat la HCC nam gidi lai cao vugt trdi so vdi nii gidi. Tuy nhien nguyen nhan nay lai khdng giai thich thda dang dugc vi sao gan day ty le nam/nii lai tang len ro ret d Viet nam?
Cung can dat gia thuyet la phai chang lam dung bia,rugu tai Viet nam hien nay cd the tham gia vao su thay ddi nay. Cd mgt sd bang chiing ling hp cho gia thuyet nay: Trong nhung nam tu 2000 den nay,lugng tieu thu bia rugu tai Viet nam tang len khdng ngimg vdi ty le cao. Din nam 2011 luong tieu thu Bia cua Viet nam dat den 2.595,4 trieu lit diing dau cac nude Ddng Nam A a vugt xa nude diing thii nhi la Thai lan (1.805,4 trieu lit) va van cdn tang vdi tdc dp cao (15).Trong nghien ciiu nay ciia chiing tdi cung cho thiy cac benh nhan HCC hien nay cd men GGT (phan nao dac hipu cho viem gan do rugu) cao vdi mot ty le bao dgng:84/92 (91%) bpnh nhan cd miic GGT vugt muc cua gia tri tren binh thudng va 68/92 (73,9%) cao tren gip doi gia tri tren cua binh thudng va tuyet dai da sd trong nhdm nay la nam gidi 64/68 (94,l%).Tr V Huy (8) trong luan an tiin sT Y hgc cho thiy d benh nhan HCC lien quan vdi HBV va/hay HCV cd din 35,8% cd dung rugu
>40g/ngay tren 10 nam.NhCimg ngudi udng
rugu nay cd nguy co xuat hipn HCC cao rndt each cd y nghTa so vdi nhdm chiing. Neu udng rugu >40g -60g/ngay tren 10 nam cd OR=5,2 (95%CI=1,1-24,6) nhung niu uong >60g/ngay tren 10 nam thi OR=IO,7(95%CI=l,3-85,2).
Tudi cua nhirng benh nhan HCC cd udng rugu tre hon nhdm benh nhan khdng udng rugu khoang 6 tudi (48,4±12,6 vs 54,4±13,5;
p<0,026). So lipu cua V.v.Vu va cs cung cho thiy 1/5 bpnh nhan HCC cd udng rugu >100g/
ngay va 1/4 cd udng rugu >50g/ngay (10).
Nhijng nghien ciiu trudc day ty Ip benh nhan HCC cd udng rugu d miic nguy hiem chi chiim khoang <10%. Day la mgt nhan xet can luu y di cd kit luan rd rang hon vi y nghia thyc tien ciia nd trong phdng bpnh qua viec giao due van dgng tren cac phuang tien truyen thdng dai chiing. Lin CW va cdng sy nghien ciiu tren 966 benh nhan xo gan gdm 3 nhdm nguyen nhan la: ddng thdi nhiem HBV va nghien rugu (132 benh nhan) - chi nhiem dan thuan HBV(632 bpnh nhan ~ va chi nghien rugu don thuan (202 benh nhan) tan xuat tich liiy HCC sau 10 nam theo thir ty la 52,8% vs 39,8% vs 25,6%;
p<0,001 (16).
Tudi cua benh nhan trong nhdm nghien cuu nay giao ddng tir thap nhat la 30 va cao nhat la 76. Tudi trung binh toan nhdm la 53,72+10,74 va khdng cd su khac biet ve tudi giiia nhdm benh nhan nam gidi va nii gidi (53,63+10,90 so vdi 54,20+23,0; p=0,9997).Kit qua nay cung phu hgp vdi cac ket qua nghien ciiu gan day d Viet nam. Tuy nhien,neu so sanh Idp tuoi ciia HCC hipn nay vdi cac nghien ciiu tai Viet nam trudc day khoang 20 - 30 nam thi tuoi trung binh ciia HCC hien nay da tang len khoang 10 tudi (7,17). Ngugc lai, Idp tudi cua benh nhan HCC d cac qudc gia Bic My va Tay Au lai la tren 60 (gia hon d Viet nam hien nay khoang 10 tudi) (18,19) mac du sd benh nhan trong cac nghien ciiu nay cd ty le ngudi chau A kha cao (>44%o)(18) hay phan tich rieng nhdm ngudi gdc Chau A (19). Cung nen luu y la trong nhdm nghien ciiu ciia chiing tdi cd 10%
benh nhan <40 tudi, tiic la Idp tudi khdng co yeu cau tam soat HCC theo khuyin cao cua AASLD (20). Ty le nay tuy khdng cao nhung vdi xuat do HCC cao cua Viet nam thi sd benh
Tap chi GAN MAT VIET NAM s6 24-2013 11
nhan trong nhdm nay trong dan sd cung tuong duong nhu toan bg HCC d nhirng nude cd xuat do HCC thip nhu d Tay Au hay Bic My.
Hon niia nhdm benh nhan trong lap tudi nay cd ty le chua xo gan cao va do do niu dugc tim soat va chan doan sdm thi cd kha nang diiu tri triet di bang phlu thugt cao. Wang Q va cs trong nghien ciiu vi 93 tnrdng hgp HCC li^n quan vdi HBV tai Bpnh vien Dai hpc Mount Sinai tai Hoa ky ciing ghi nhan cd 18 bpnh nhan (19,4%) <40 tudi - hie la trong Idp tudi khdng nim trong dipn tim soat HCC cua AASLD nen toan bd nhdm benh nhan nay khi dugc chan doan HCC khdng cdn kha nang diiu trj tript de bang phau thuat hay ghep gan m$c dau 12/18 (66,7%) bpnh nhan trong nhdm nay HCC phat trien tren nen gan khdng xo. Bdi v^y tac gia de nghi thay ddi lai khuyin cao tim soat HCC cua AASLD d Idp tudi sdm hon (21).
Nhieu nghien ciiu cdng bo tnrdc day d Viet nam ciing cho thay ty le benh nhan HCC d Idp tudi <40 chiim tir 20 din 25% (9,22,23). Theo chiing tdi tudi tam soat HCC lien quan vdi HBV d Viet nam sau nay neu cd nen bat dau tir 35 la hgp ly hon.
Dau an huyet thanh AFP trong nhdm nghien ciiu nay.
AFP la mdt khang nguyen bao thai, ma sy xuat hipn/tang len sau nay tren ca the cd lien quan vdi xuit hien HCC. Abelev G la ngudi diu tien phat hien mdi lien quan nay tren chudt nghien ciiu sau do Tatarinov YS da thiy tren benh nhan HCC cd tai xuat hien AFP va diing nd nhu mdt dau an de chan doan HCC. Trong cac thap nien 1960-1980, AFP dugc dung rdng rai ca trong tam soat va chan doan HCC trong lam sang. Tuy nhien, nhirng nam gan day vdi sy phd biin va tiin bd nhanh chdng cua chan doan hinh anh hgc ciing vdi kha nang phat hien sdm HCC bing cac ky thuat hinh anh hgc, vi tri cua AFP va cac diu in huyet thanh khac nhu DCP, AFP-L3 da bi thu hep lai rit nhiiu trong ca tim soat ciing nhu chin doan HCC va bang chimg rd nhit la AASLD da khdng xep xet nghiem AFP trong tim soat HCC(20).
R.Takeishi va cs trong mdt nghien ciru gdp tap hgp tai heu trong 20 nam tir 1982 di 2002 nhim so sanh y nghia lam sang ciia 3 dau an
huyit thanh la AFP,DCP (desgamma Carboxy Prothrombin), AFP-L3 (Len Culmaris AFP) va nguong toi uu ciia chiing trong chan doan HCC dua din kit luan la thii ty gia tri chan doan HCC tang din tir AFP rdi DCP va cao nhit la AFP-L3 .Nguong tdi uu cho chan doan tuang ling ciia 3 diu an huyet thanh tren la 200ng/ml, 40AU/ml va 15% (24). CJ Viet nam, theo chd chiing tdi biet chua cd cdng trinh nao nghien ciiu ve gia tri ciia DCP trong chan doan HCC.
Trudc day, d Benh vien 108 V.v.Khien va cs cd nghien ciiu tren 65 bpnh nhan HCC ve gia tri ciia AFP-L3 va cung cd nhan xet cd gia tri chan doan HCC cao hon so vdi AFP (25) nhung khdng cd nghien ciru nao tiep theo. Tren the gidi, ngoai Nhat ban cac nude khac ciing khdng cd nhieu nghien ciiu ve dau an ciia DCP va AFP-L3 va trong thdi dai ciia cac ky thuat hinh anh hpc chan doan sdm HCC ngay nay, nghien ciiu ve dau an huyet thanh hgc trong chan doan HCC khdng cdn mang tinh thdi sy niia. Hien nay, hinh anh ddng cua CT/MRI cd bom thudc can quang la hij cot trong chan dan HCC sdm.Hinh anh dien hinli/kinh dien cua HCC trong ky thuat CT hay MRI cd bam thudc can quang (Contrast Enhanced CT/MRI) cua HCC cd kich thudc >2cm la tang can quang thi dgng mach va giam can quang thi thi tmh mach/thi cham cho dp nhay va tien doan duong tinh khoang 93% va >97% vi vay cho phep cac bac sT lam sang xu ly nhu HCC ma khdng can den ket qua md hoc. Tieu chuan chan doan hinh anh hpc nay dugc ca 4 hdi Gan Mat ldn cua the gidilaAASLD,EASL-EORTC,APASLva hpi gan Nhat ban (The Japan Society of Hepatol- ogy = JSH) chip nhan (26,27,28,29) .Trong 130 benh nhan HCC cua nghien ciiu nay cd 92/130 (70,8%) cd chin doan bing hinh anh ddng CT/MRI ma khdng cd sinh thiet, sd cdn lai dugc chan doan vdi hinh anh khdi u gan dudng kinh >5cm vdi AFP > 400ng/ml. Gin day ban cap nhat dong thuat cua AASLD da cho phep quyet dinh chan doan khdi HCC tir
> I cm dudng kinh va chi can mdt ket qua binh anh dien hinh ma thdi (30). Mgt sd nghien ciiu cho thay cd the diing ky thuat sieu am cd bam thudc cam quang (CE-US ^ Contrast Enhanced Ultrasound) cho chan doan sdm HCC nhung
12 TapchiGANMATVIETNAMs624-2012
hien khdng dugc cdng nhan rdng rai vi do nhay va do dac hieu thap hgn c^c ky thuat sir dyng CE-CT/MRl (32,33) va cung chua hien hiru d Viet nam. Gia tri ban chi ca trong tjm soat va chan doan cua AFP ngay nay chua dugc luu y dung muc tai Vi?t nam, nhat la d cdc dia phucmg vi vay lam chg mgt sd b?nh nhan dugc chan doan mudn HCC thay vi cd the chan dodn sgm hon. Cd 2 hudng suy nghT lenh lac thudng gap la chi dya vao AFP trong truy lung HCC d benh nhan cd nguy eg HCC hoac phat hi?n c6 khdi u tren hinh anh nhung AFP d muc binh thudng nen khdng di sau them de chan doan xac djnh HCC.Vdi mdc AFP >20ng thudng dugc sir dung trong tam soat HCC nhung nhu vay benh nhan cd AFP <20ng khdng cd nghTa la khdng phai HCC va khdng can tam soat them bang hinh anh sieu am. Ngugc lai, gidi han tdi uu trong chan doan HCC cua AFP la
>200ng hay >400ng /ml cung khdng ddng nghTa vdi viec nhan djnh day la moc gidi ban giira chan doan xac dinh va loai tru.
Dau an huyet thanh HBeAg duong tinh la mgt chi din chiing td HBV dang cd hoat dgng tang smh va thudng kem vdi cd HBV DNA cao tren lO^cps/ml.Tuy nhien ngoai chi din vl sy boat ddng tang sinh cua virus, ban than khang nguyen HBeAg cdn cd cac cac hoat tinh sinh hgc khac nhu tao ra su dung nap ciia co the vdi HBV,uc che hoat dgng cua mien dich tu nhien,hudng hoat tac miln dich theo Tpj2 (34). Dot biln viing BCP hay PC la nhiing dot bien tu nhien trong qua trinh nhiem man tinh ciia HBV din din lam giam hay mit HBeAg va xuit hien anti HBeAg trong da sd cac trudng hgp chiing td co thi da cd dl khang mdt phan vdi su tang sinh ciia HBV (35). Vi vay ty le duong tinh HBeAg giam din vdi tudi benh nhan. Ngoai ra ty le nay cung cdn thay ddi theo typ gen cua HBV vi vay cin so sanh vdi nhdm benh nhan ciing tudi va ciing cd nhiem cac typ gen HBV tuong tu. Benh nhan HCC lien quan vdi HBV cua chiing tdi cd ty le duong tinh HBeAg la 26/81 (32,1%) va lap tudi trung binh la 54. So vdi ty le cd HBeAg dugng tinh cua benh nhan nhiem HBV man tinh khong HCC ciing dugc tien hanh tai Benh vien DH Y Dugc cua DD Hai g Idp tudi >40 la 20,9% (42/201).
NIU liy so lieu nay lam ddi chiing thi su hien di?n HBeAg+ tren benh nhan Vi$t nam g Idp tuoi >40 cd nguy eg tang HCC vdi OR=l,7869; 95% CI: 1,0047 - 3,1876 va p<0,05 (36).HI Yang va Cs tai Dai loan nghien cuu tuyIn chgn ddi tugng trong cpng ddng tit 1991 -1992 va kit thiic vao 9/2000. Xet nghiem ban diu gdm HBsAg va HBeAg.Tdng sd cd 47.079 ddi tugng nam giai,tudi 35-60 nhung chi 11.893 (25%) tham gia nghien cuu.Tinh chung cd 92.358 lugt ngudi/nam.Ty le HBeAg+/cd HBsAg duong tinh la 39%. Tin xuit phat sinh HCC hang nam trong nhdm b?nh nhan duong tinh ddng thdi HBsAg va HBeAg la 1169/100.000 (RR= 29,97) so vdi nhdm b?nh nhan chi duong tinh vdi HBsAg la 324/100.000 (RR=8,31) va nhdm am tinh vdi ca HBsAg va HBeAg la 39/100.000 (lam ddi chiing RR=1).
Ket qua sau khi da dieu chinh tudi, gidi, HCV, hiit thudc,udng ruau thi nguy eg bi HCC la:
0R= 9,6 (0,95 CI = 6,0 - 15,2) khi chi duong tinh HBsAg
0R= 60,2 (0,95 CI = 15,5 - 102,1) khi ducmg tinh kep HBsAg va HBeAg (37).
M.W Yu, S.H Yeh va cgng sy nghien cihi tren cac ddi tugng la nam gioi >30 tudi tir nhdm 4841 ddi tugng trong 14 nam theo doi phat sinh 154 HCC va so vdi 316 ddi chiing cho thay cimg cd HBsAg nhdm cd HBeAg duang tinh nguy co HCC tang len vdi 0R=2.13 (95%CI= 1,09 - 4,18)
Tac gia cdn cho thay ciing nhirng benh nhan cd HBeAg am tinh thi neu cd anti HBe duang tinh se giam nguy co HCC khoang 70% vdi OR=0,29 (95%CI=0,17 -0,45)(38).You S.Lva cdng sy trong nghien ciiu trudng hgp ddi chiing giira nhdm benh nhan thudng xuyen duong tinh ddng thdi ca HBsAg va HBeAg vdi nhdm chi duong tinh rieng vdi HBsAg cd phan tang theo miic ALT.xg gan va suy doan ty le tich luy ddn HCC tir 30 din 70 tudi tuang ling la 87%! cho nhdm cd duong tinh kep va 12%
cho nhdm chi duang tinh vdi HBsAg cdn nlu am tinh vdi ca 2 diu In thi chi phat sinh HCC 1% (39).Tsai JF va cs thiy cac dgt biln tren khang nguyen HBs lam bd sung them tinh gay
Tap chi GAN MAT VIET NAM s6 24-2013 13 HCC cua HBeAg (40).
Nhimg nghien ciiu gdn day cho thay y nghia mdi ciia HBsAg bang dinh lugng,nd phan anh tinh trang cccDNA ciia HBV va ddng thdi ndi len tinh trang dap ling mien dich cua benh nhan vdi HBV trong diiu tri vdi Peg Interferon (41,42).Tren 86 benh nhan HCC ciia chiing tdi cd dinh lugng HBsAg thi cd 60/86(69,8%) cd lugng HBsAg >1000IU/ml, nhiing benh nhan nay dii cd HBV DNA thap van cd nguy co bi HCC cao.Yiu td tien doan HCC tren benh nhan nhilm man tinh HBV cd ca vai trd ciia lugng virus phan anh qua HBVDNA va lugng HBsAg. Dac bipt tren nhdm benh nhan cd lugng HBVDNA < 10" cps thi lugng HBsAg cd y nghTa dy doan tdt han. Lin CL va cdng sy xu dung lai sd lieu tir REVEAL-HBV cho thiy ca mire HBVDNA va qHBsAg bd sung cho nhau trong yeu td tien doan xuat hipn HCC tren benh nhan nhiim HBV man tinh. Gia tri tien doan phat sinh HCC ciia HBV DNA tdt hon khi lugng HNB DNA >10'' cps/ml (hay
>2000IU/ml) ngugc lai khi HBV DNA thip hon so tren thi qHBsAg lai cd gi^ tri tdt hon (43).
Tseng TC va Cs xac nhan vai trd ciia tien doan phat sinh HCC trong nhom benh nhan nhilm HBV cd lugng HBV DNA thip hon 10"
cps/ml. Tren nhdm benh nhSn HBeAg am tinh vdi HBVDNA <10'' cps/ml khi c6 HBsAg>1000IU/ml so vdi bpnh nhan co HBsAg <1000IU/ml lam tang nguy co HCC vdi OR=]3,7; 95%CI: 4,8 - 39,3; p <
0,001.(44)
Lugng HBV DNA fren 130 benh nhan HCC lien quan vdi HBV cua chiing tdi thay ddi tii am tinh din tai lugng rat cao dat tdi >10^
cps/ml. Mdc quan trgng cua tai lugng HBV lam gia tang ro rpt nguy co HCC theo nghien ciru REVEAL-HBV la tir > 10" cps /ml thi nhiing benh nhan cua chung tdi cd 78/130 (60%) va nguang nguy ca cao nhat la > 10* cps thi chiing tdi cd 35/130 (26,9%).Tuy nhien mdt sd bpnh nhan ciia chung tdi cd tai lugng HBV DNA thip <10'' cps/ml dugc dinh lugng HBsAg cho thiy cd 40% c6 lugng HBsAg
>1000IU/ral. Nhiing benh nhan cd tai lugng HBV DNA thip < 10" cps khdng c6 trudng hgp
nao cd HBeAg duong tinh. Nhu vay, khi gdp 2 tieu chuin HBV DNA va lugng HBsAg, udc tinh bpnh nhan cua chiing tdi cd 76% trong nhdm cd tieu chuan nguy co rat cao phat sinh HCC va niu nhu cd chuang trinh tam soat HCC chiing ta cd the phat hien sdm va theo do hieu qua diiu tri se tdt han. Nghien ciiu REVEAL-HBV tai Dai loan la mgt nghien cim diln tiin ty nhien cua benh nh^n nhiem HBV man ca the HBeAg duang tinh va am tinh trong cdng ddng dac bipt quan trgng va hau nhu khdng thi lap lai vi sd lugng theo doi ldn 3700 benh nhan vdi thdi gian theo ddi > 10 nam va khdng cd dieu tri dac hieu do liic dd chua cd thudc dac tri. Ddi vdi Viet nam nd lai cang cd y nghia khi cac typ gen HBV ciing chi gdm HBV- typ gen B va HBV- typ gen C.MW Yu va cdng sy trong mdt nghien ciiu tien ciiu d 4841 benh nhan nhilm HBV man nam gidi Dai loan chua bi HCC sau thdi gian theo doi trung binh la 12 nam c6 154 HCC phat sinh, tac gia chgn ra 316 chiing khdng HCC ( ty le benhxhiing la 1:2). Khi phan chia HBV DNA lam 5 miic tinh theo logjQ cps/ml tir am tinh den 3,61 log lam mdc vdi nguy ca la 1; tiep theo la cac miic tu 3,62 den 4,22 - tir 4,23 den 4,90 - tir 4,91 din 5,90 va >5,90 din 10,81 nguy ca HCC tang din vdi OR la lugt la 1,07 (p>0,05); 2,54 (p,0,05); 2,44 (p,0,05); 7,25 (p<0,0Dl)(45).
Mdt sd dac diem sinh benh hgc ciia cac typ gen khac nhau da dugc CJ Liu,JH Kao neu trong phan tich tdng quan cho thay HBV cd typ gen C cd nguy ca gay HCC cao hon, thudng benh tiet trien nang hon va ty chuyen ddi huyet thanh HBeAg cham hon. Tuy nhien d nhdm benh nhan HCC tre <50 tudi thi thudng gap typ gen B (46).Trong tdng sd 130 benh nhan HCC lien quan vdi FIBV cua chiing tdi chi dinh dugc typ gen tren 77 benh nhan,sd khdng dinh dugc typ gen hau het la do tai lugng HBV thap. Phan bd cac typ gen cho thay typ gen B la 44/77 (53,2%); ddng thdi cd 2 typ gen B va C la 13/77(16,9%) va typ gen C la 23/77(29,9%).
Vi ky thuat dinh typ gen ciia chiing tdi su dyng trong nghien ciiu nay la ky thuat Multiplex nen sy xuat hipn ddng thdi 2 typ gen la sy cd mat ddng thdi HBV cua 2 typ B va C ma khdng
Tap chi GAN MAT VIET NAM so 24-2012
phai do sy tai td hgp ciia 2 typ gen tren .Trong nghien ciiu cua chiing tdi cung cho thay nhdm tudi thap nhat la benh nhan c6 typ gen B (52,49 tudi) rdi nhdm bpnh cd typ gen B+C (43,72 tudi) va cao nhat la nhdm bpnh cd typ gen C (55,52 tudi) tuy nhien su khac bipt nay chua cd y nghTa thdng ke.
Sy xuat hipn ddng thdi 2 typ gen B va C tang len tren nhdm bpnh nhan nhiem HBV mac HCC ciing da dugc nhan xet trong nghien ctiu ctia DTK An va cgng sy tren 409 benh nhan thugc eac the lam sang khac nhau tir dung nap
mien dich,viem gan B cap,viem gan B man.xo gan va HCC. Chi trong nhdm benh HCC cd ty le typ gen B+C tang cao din 10/51 (19,6%) cdn trong cac the lam sang khac cua ca benh nhan d miin nam cung nhu mien bac chi chiem tir 0 din <3% (47).Sy khac biet cd y nghia thdng ke cao. Liy vi du so sanh cac typ gen HBV trong HCC cua nghien ciru nay vdi bpnh nhan viem gan B man ciing tien hanh tai bpnh vipn DH Y Dugc Tp HCM (47) vdi ciing ky thuat ta cd kit qua dugc trinh bay trong bang 3:
Bdng 2: So sdnh typ gen cua HBV a benh nhdn viem gan vd HCC.
Typgen HCC VGB man
B 44 84
B+C 13 0
C 23 23 : 22,1 vdi p< 0,000
Nguy CO cao HCC d benh nhan cd dong thdi 2 typ gen B va C chiing tdi chua thay neu trong y viin va ly do vi sao hien nay ciing cdn chua cd cau tra Idi ro rang.
Trong nghien ciiu nay chimg tdi chi nghien cim mgt loai dot bien kep tu nhien tren viing Idi vi chung cd anh hudng len nguy co xuat hien HCC da dugc nhieu tac gia cdng bd. Tren 54 benh nhan HCC cd ket qua vl dot biln kep A1762T/G1764A thi cd 31/54 (57,4%) cd ddt biln va 23/54 (42,6%) d thi hoang dai. Ty le cd dot biln tang din theo typ gen tit thip len cao la typ gen B roi typ gen B+C va cao nhit la typ gen C (theo thir tu lin lugt la 48,1% rdi 58,3%va 73,3% nhung vi sd mlu gidi ban nen sy khac biet nay chua cd y nghTa vl thong ke (p^0,286). Khi ddi chieu vdi ty le dot biln nay cua LT Phuong va Cs tren benh nhan viem gan B man tinh tai Benh vien nhiet ddi Tp HCM la 53/216 (24,5%) thi sy khac biet la cd y nghTa thdng ke (p<0,000) va OR=3,383 vdi 95% CI:
1,8875-6,0636 (48). Nhu vay.theo kit qua thu 5. Ket luan.
Benh nhan HCC lien quan vdi HBV trong nghien cira nay cd ty le nam/nir cao din 9/1 ddng thdi ty le cd men GGT cao tren binh thudng la >91%. Dac dilm nay gai y vai trd
dugc thi sy xuat hien dot bien kep A1762T/G1764A tren benh nhan viem gan B man lam tang nguy eg xuat hi?n HCC len khoang gan 4 ian. Benh nhan HCC cua chiing tdi khdng cd khac biet nhau ve mdi va tham chi nhdm cd dot bien kep cdn cd tudi trung binh thap hon (51,2 tudi so vdi 54,2 tudi). Tac gia JG Chen va Cs theo ddi tren benh nhan viem gan B man thay su xuat hien dot biln kep nay xay ra hang chuc nam trudc khi xuit hien HCC vi vay day la mdt dau an tdt cho tim soat benh nhan viem gan B cd nguy ca HCC cao ban nira nhirng benh nhan cd dot bien kep nay thudng tu vong d mdi sdm ban (49).Munos A va Cs nghien ciru trudng hgp ddi chirng gdm 345 benh nhan HCC va 625 chiing. Ty le cd dot biln kep nay tren nhdm benh la 81 % (278/345) va tren nhdm chimg la 40% (250/625). Theo ket qua nay tac gia cd kit luan nguy co HCC cua dot biln kep nay la OR=6,72 ; 95% CI:
4,66-9,68) (50).
cua bia rugu va cac hdi chiing chuyin hda co thi lam gia tang HCC tren benh nhan nhilm HBV can dugc nghien cim them
10% benh nhan HCC d Ilia tudi <40.
Tap chi GAN MAT VI$T NAM s6 24-2013 15
Ty le AFP tren > 400ng/ml d benh nhan HCC chiem 30,4% nen gia tn chan doan rat han che. Phan ldn benh nhan chin doan xac dinh dugc dya vao dac trung ciia hinh anh CT/MRI cd bam thudc.
Cac dac diem ve virus hpc deu cho thay cd nhiing yeu td nguy co HCC tren nhdm benh nhan nay nhu ty le cd HBV DNA > 10" cps/ml chiem tdi 60% va nhdm benh nhan cd HBV
DNA thap thi 40% cd HBsAg cao tren 1 OOOIU/ml. Ty le cd HBeAg duang tinh,cd typ gen C va B+C cung nhu dot bien BCP deu cao hon mdt each cd y nghia so vdi nhdm ddi chiing lich sir bi viem gan virus B chua bien chiing HCC lam ddi chiing. Nhirng d^c diem nay cd the giiip phat hien nhdm bpnh nhan nhiem HBV cd nguy co cao de tam soat HCC sau nay.
Tai li@u tham khao.
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