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 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 . 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. 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% 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 -