NH GI HIU QU FORTEC TRONG IU TR VIM GAN

B mn Ni tng hp - Trng i hc Y H Ni Khoa Tiu ha-Bnh vin Bch Mai Tp ch Y Hc Thc Hnh - B Y T - S 7 (727/2010)

Mc tiu: nh gi hiu qu iu tr ca BDD (Fortec) da trn triu chng lm sng v cn lm sng bnh nhn vim gan. i tng v phng php nghin cu: Nghin cu tin hnh t thng 05/2008 n thng 11/2008 trn 30 bnh nhn c chn on xc nh vim gan iu tr ni hay ngoi tr ti khoa tiu ha Bnh vin Bch Mai v Bnh vin i hc Y H Ni. Bnh nhn trong nghin cu c iu tr theo phc thng nht 4 vin Fortec/ mt ngy chia 2 ln trong 4 tun. Kt qu iu tr vi men gan c chia thnh 3 mc : p ng hon ton, p ng mt phn v khng p ng Kt qu v bn lun: BDD- Fortec c tc dng ci thin r rt triu chng lm sng ca vim gan: trc iu tr BN c chn n (63,3%), chng bng (33,3%), mt ng (30%), au vng gan (30%); sau iu tr cc triu chng ca hi chng suy t bo gan gim c ngha thng k vi p<0.01; chn n gim xung cn (13,3% vi p< 0,01), chng bng (3,3% vi p< 0,01), mt ng (13,3%), au vng gan (6,6%). Fortec lm ci thin ng k s suy gim chc nng gan v s hy hoi t bo gan: Trc iu tr; ALT / mu trung bnh l 281,56 317,63 IU/lt v AST/ mu trung bnh l 209,94 188,33 IU/lt. Sau iu tr; ALT trong mu trung bnh l 61,32 56,76 IU/lt vi p< 0,01 v AST trong mu trung bnh l 40,03 20,15 IU/lt vi p< 0,01. Fortec cn c tc dng lm gim bilirubin mu v ci thin nng albumin mu. Kt lun: Cng vi cc bin php iu tr c hiu vim gan, BDD-Fortec c tc dng ci thin ng k triu chng vim gan v hi chng hy hoi t bo gan Sumary: Effect of Biphenyl Dimethyl Dicarboxylate (Fortec) in Chronic Hepatitis Patients Aims: to assess the effect of Biphenyl Dimethyl Dicarboxilate (BDD - Fortec) base on clinical symptoms and laboratory results in hepatitis patient. Patients and methods: the study was conducted 30 hepatitis patients at the Gastro-intestinal Department, Bach Mai Hospital and Hospital of Hanoi Medical University from May to November 1

2008. We used descriptive study. Patients were taken twice per day of four tablets Fortec during 4 weeks. Compliance and side effects were evaluated at the same time The regular follow up of liver performed. Results and Discussions: After 4 weeks treatments of Fortec, the symptoms of hepatitis were significantly decreased: Symptom before treatment: appetite (63,3%); abdominal floating (33,3%); Sleeplessness (30%); Liver area pain (30%). Symptom after treatment: appetite (13,3% with p< 0,01); abdominal floating (3,3% with p< 0,01); Sleeplessness (13,3%); liver area pain (6,6%) Serum AST, ALT level were also decreased : Before treatment: ALT: 281,56 317,63 IU/liter and AST: 209,94 188,33 IU/liter After treatment: ALT: 61,32 56,76 IU/liter with p< 0,01 and AST: 40,03 20,15 IU/liter with p< 0,01 Serum albumin, bilirubin were changed. Conclusions: Biphenyl Dimethyl Dicarboxilate (Fortec) was strongly reduced ALT and AST as well as relieved of the clinical symptoms, included appetite, abdominal floating, sleeplessness and liver area pain in hepatitis patients. T VN Gan l c quan m nhim rt nhiu chc nng quan trng ca c th: tng hp, chuyn ha v c bit l chng c. Cc tc nhn gy hi cho gan c rt nhiu trong phi k n ru v vim gan virus. Vim gan l bnh hay gp trong thc tin lm sng trn th gii cng nh ti Vit Nam vi hu qu to ln l x gan, K gan lm gim chc nng ca gan v nh hng nhiu n chc nng khc ca c th. Cc thng k cho thy trn th gii c hn 350 triu ngi mc vim gan B v 170 triu ngi vim gan C vi t l pht trin thnh x gan v ung th gan sau 10-15 nm thay i t 85-100%. cc nc pht trin nguyn nhn ch yu l do ru tip sau l do vim gan virus C v B. Ngc li, 75% cc trng hp vim gan B l cc nc ang pht trin trong c Vit Nam vi tc nhn gy bnh hng u l do virus vim gan B,C ri mi n nguyn nhn do ru. Vic iu tr vim gan do virus cn gp rt nhiu kh khn. Trong khi vic s dng cc thuc iu tr c hiu tiu tn nhiu tin m cng ch mang li kt qu hn ch th cc thuc iu tr h tr lm gim cc triu chng cng c mt vai tr nht nh lm tng cht lng cuc sng ca ngi bnh. Fortec l mt cht tng hp tng t nh Schisandrin C. y l thnh phn c phn lp t qu ng v t (Fructus Schisandrae), mt loi thuc c truyn ca Trung Quc. Fortec c tc dng c ch phn hy t bo gan do lm gim triu chng c nng cng nh biu hin trn cn lm sng bnh nhn vim gan [2]. V vy chng ti tin hnh nghin cu nhm mc tiu: nh gi hiu qu iu tr ca Fortec i vi cc triu chng lm sng vim gan v s ci thin chc nng gan. Nhn xt v s dung np thuc v tc dng ph ca Fortec trong qu trnh iu tr I TNG V PHNG PHP NGHIN CU 1. i tng nghin cu : Trong thi gian t thng 5/2008 n thng 11/2008 chng ti tin hnh nghin cu trn 30 bnh nhn c chn on vim gan do: virus vim gan B, C hoc do ru. Tiu chun la chn bnh nhn - T 18 tui tr ln, t nguyn tham gia nghin cu - c chn on vim gan do virus hoc do ru - C ALT 80 IU/L - Ch iu tr n thun bng fortec Tiu chun loi tr - Bnh nhn vim gan c bilirubin ton phn >100mol - Bnh nhn ung th gan - Bnh nhn tin hn m gan 2

Bnh nhn c km thm cc bnh ni khoa nng khc nh suy thn, suy tim, ung th hoc cc bnh cp cu - Ph n c thai hoc ang cho con b 2. Phng php nghin cu: Tt c bnh nhn tiu chun la chn c cho ung Fortec 25mg, 4 vin/ngy chia 2 ln sau khi n sng v n tra, trong 4 tun. Tin hnh theo di: nh gi lm sng trc v sau iu tr, bao gm cc triu chng c nng nh: chn n, mt mi, mt ng, au vng gan. Xt nghim sinh ha mu trc v sau iu tr : Creatinine, bilirubin ton phn, bilirubin gin tip, bilirubin trc tip, protid, albumin, prothrombin, AST, ALT. nh gi mc p ng ca ALT: - p ng hon ton: l khi ALT tr v bnh thng hoc gim c >75% - p ng mt phn: l khi ALT gim t 50-70% - Khng p ng l khi ALT gim t hn 50% 3. X l s liu bng phng php thng k y hc vi phn mm SPSS version 10.0 KT QU Tng s bnh nhn p ng theo ng tiu chun ca nghin cu l 30 bao gm 21 nam v 9 n, t l nam/n l 2,3/1. Tui trung bnh ca bnh nhn l 43.03 14.94 (22-70 tui). 1. Hiu qu trn triu chng lm sng ca vim gan: Chng ti thu nhn c 30 BN vim gan trong c 18 BN vim gan B, 8 BN vim gan do ru, 2 BN vim gan C, 2 BN vim gan B v ru. Trc khi iu tr: 100% c triu chng mt mi, 63,3 % bnh nhn c cm gic chn n, 33% chng bng, 30% mt ng v 30% bnh nhn c cm gic au vng gan.
Trc iu tr Sau iu tr

100.00% 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% 13.30% 3.30% Chn n Chng bng 63.30%

100%

33.30%

30% 13.30%

30%

30.40%

6.60% Mt ng au HSP Mt mi

Biu 1: Triu chng lm sng vim gan trc v sau iu tr Fortec nhm BN nghin cu Nhn xt: Sau iu tr Fortec 4 tun, triu chng mt mi, chn n v chng bng c ci thin c ngha thng k vi p<0.01. Triu chng au h sn phi gim i c ngha vi p<0.05. Fortec lm gim triu chng mt ng ca BN vim gan, tuy nhin s khc bit ny khng c ngha thng k. 2. Hiu qu iu tr trn xt nghim sinh ha: 2.1.Hiu qu trn nng AST v ALT. 3

Trc iu tr tt c cc BN ca chng ti u c tng men gan vi mc khc nhau: ALT trung bnh trc iu tr l 281,56 317,63 IU/L v AST l 209,94 188.33 IU/L. Bng 1. Thay i AST; ALT trc v sau khi iu tr bng Fortec 4 tun Xt nghim mu AST (IU/L) ALT (IU/L) Trc iu tr 209,94 188.33 281,56 317,63 Sau iu tr 61.32 56,76 40,03 20,15 P P < 0,01 P < 0,01

Nhn xt: Fortec vi liu 100mg trong 4 tun c tc dng lm gim r rt men gan AST, ALT. S khc bit ny c ngha thng k vi p<0,01 Bng 2: Mc gim ca ALT S lng BN n T l % p ng hon ton 16 63,3 p ng mt phn 9 20 Khng p ng 5 16,7

Biu 2: Mc p ng qua men ALT sau iu tr Fortec 4 tun

HT MP K

16.70%

20%

63.30%

Nhn xt: 63% s bnh nhn sau khi iu tr c ALT tr v bnh thng hoc gim >75%, 20% bnh nhn c ALT gim 50-70% v 16,7% c ALT gim <50%. 2.2. Hiu qu iu tr trn Bilirubin mu, albumin huyt thanh v t l Prothrombin Bng 3: Xt nghim chc nng gan trc v sau iu tr Fortec Xt nghim mu Trc iu tr Creatinine( mol/l) 74,79 17.54 Bilirubin ton phn 32,66 58,48 (mol/l) Bilirubin gin tip 17,6 31.02 (mol/l) 4 Sau iu tr 78,69 16,4 15.32 8,71 8,78 4,38 P P > 0,05 P > 0,05 P > 0,05

Bilirubin trc (mol/l) Protid (g/L) Albumin (g/l) Prothombin (%)

tip 15,01 28,78 74,33 15,30 42,17 5,38 101,76 27,06

6,54 6,95 79,84 6,61 43,52 5,37 105,79 20,94

P > 0,05 P > 0,05 P > 0,05 P > 0,05

Nhn xt: -Trc v sau iu tr gi tr ca creatinine thay i khng c c s khc bit c ngha thng k vi P>0,05. -Sau iu tr Fortec 4 tun, cc BN c gim bilirubin mu tuy nhin s khc bit ny khng c ngha thng k, -Chng ti khng nhn thy c s khc bit v protid, albumine, t l prothrombine trc v sau iu tr BN LUN Nh chng ta bit hoi t t bo gan do bt k nguyn nhn g u t nhiu lm suy gim chc nng gan gy nhng triu chng c nng quan trng nh hng n kh nng lao ng ca ngi bnh. Ti Vit Nam theo thng k ca B y t vi gn 16 triu ngi vim gan B cng vi nhng trng hp vim gan do ru cng ngy cng gia tng t ra mt vn ln cho sc khe cng ng v cho ngnh y t. Vn iu tr vim gan rt phc tp v cn phi c s thu hiu gia thy thuc v bnh nhn. Vic iu tr bnh nguyn l yu t chnh ngn nga cc tn thng gan mn cng vi hu qu lu di l x gan v ung th gan. Tuy nhin trn thc t lm sng, yu t lm cho bnh nhn lo lng nhiu nht chnh l xt nghim men gan. V vy cng vi cc bin php iu tr c hiu vim gan virus hay ngng ru r rng cc thuc bo v t bo gan v chng oxy ha gii quyt c mt thc tin lm sng l lm ci thin cc triu chng c nng ca vim gan v a cc xt nghim sinh ha tr v bnh thng, nhanh chng to lng tin cho bnh nhn i vi BS trong qu trnh iu tr. Cc thuc bo v t bo gan xut hin t lu v c tc dng khc nhau trong qu trnh iu tr vim gan: T nhng bi thuc dn gian, actiso, cy ch rng ca, cc bit dc bo v t bo gan nhanh chng p ng mc tiu iu tr vim gan. Fortec vi thnh phn chnh l Biphenyl Dimethyl Dicarboxylate c tc dng c ch s hy hoi t bo gan, ci thin s suy gim chc nng gan v cc triu chng vim gan, lm gim nhanh men gan. Fortec cn lm bn vng mng t bo gan, bo v t bo gan khi cc tn thng do cht c, tng cng chc nng kh c ca gan. . Fortec -Bn vng mng TB gan do c ch Peroxyd ha Lipit, hy cc gc t do v mi lin kt cng ha tr gia cht c vi gan v microsom gan TB ni m

T bo gan

T bo Kufferr Mch mu

TB hnh sao

Nghin cu ca chng ti tin hnh trn 30 BN vim gan iu tr Fortec trong 4 tun cho kt qu rt kh quan : cc triu chng mt mi, chn n, chng bng, au vng gan gim mt cch r rt. Trc iu tr 63,3% bnh nhn c chn n, sau iu tr ch cn 13,3%. Trc iu tr 33,3% bnh nhn c chng bng, sau iu tr ch 3,3 % cn cc triu chng ny. Ch c 6,6% s bnh nhn c au vng gan sau khi iu tr so vi 30% bnh nhn c triu chng ny trc khi iu tr. Trc khi iu tr 30% s bnh nhn b mt ng, sau khi iu tr ch cn 13,3%. iu ny ng gp rt ln cho qu trnh iu tr lm gim lo lng cho bnh nhn v tnh trng bnh. Nh vy cng vi thuc iu tr c hiu, Fortec c tc dng nng cao cht lng cuc sng bnh nhn vim gan, triu chng mt mi v chn n c ci thin r rt hu ht cc bnh nhn nghin cu ca chng ti. Mt s nghin cu nh gi hiu qu iu tr Fortec, cc tc gi nhn thy, sau iu tr cc tn thng gan mn c ci thin phn no: tn thng thoi ha a axit, cc th a axit v nhng tn thng hoi t t bo gan cng gim bt. Cc nghin cu trn th gii cho thy sau iu tr vi Fortec, t l BN c ALT tr v bnh thng sau 1,2,3 thng tng ng l 79.8%, 81.8%, 85% trong khi t l ny nhm chng l 17%, 18% v 15%. S khc nhau gia nhm dng Fortec v nhm chng c ngha rt ln v thng k [trch 4]. Nghin cu ca chng ti khng c iu kin tin hnh sinh thit gan trc v sau iu tr tuy nhin cc xt nghim nh gi chc nng gan cho kt qu rt r rt ca Fortec vi cc ch s nh gi chc nng gan Tt c bnh nhn sau iu tr c gim ALT v AST mt cch ng k. Nng AST v ALT gim c ngha thng k vi p<0.01 (Bng 1). Nhn xt v p ng ca ALT sau iu tr Fortec 1 thng chng ti nhn thy: 63,3% s bnh nhn sau khi iu tr c ALT tr v bnh thng hoc gim >75% v 20% s bnh nhn c gim t 50-75% (Bng 2, biu 2). Nghin cu ca Jung, Choi v cng s trn 46 BN vim gan, cc tc gi nhn thy mc gim ALT l 61% thng th nht, 65% thng th 2, 83-97% thng th 3 v th 4 [trch 2]. Mt nghin cu khc ti Hn Quc trn 95 BN vim gan, cc tc gi cng t c 63.6% BN vim gan gim ALT c ngha thng k thng th nht v 80.8% thng th 2 [trch 4]. Nghin cu ca Quch Thanh Lm trn 42 trng hp vim gan mn dng Nissel tc gi t c t l p ng hon ton cao hn chng ti 81.8%, p ng mt phn 50% v 9% khng p ng [1] . Mc p ng hon ton ca chng ti thp hn so vi tc gi Quch Thanh Lm v cng s. S khc bit ny c th l do trc khi iu tr ALT bnh nhn ca chng ti l 281,56 317,63 cao hn so vi ALT bnh nhn ca Quch Thanh Lm l 198,46 124,06. Nghin cu ca Lee trn 66 BN vim gan mn cng nhn thy c s ci thin r rt ca BDD trn triu chng lm sng v AST, ALT [3]. Chng ti khng nhn thy c s thay i v Protit, albumin mu v t l Prothrombin nhm BN dng Fortec 100mg/ngy* 4 tun. Nng Bilirrubin huyt thanh c gim tuy nhin s khc bit khng c ngha thng k. Mt s nghin cu li cho thy dng Fortec t c 80% BN c nng Bilirubin mu cao tr v gii hn bnh thng, 5% c ci thin v 15% khng p ng sau iu tr [trch 5]. Nghin cu ca Quch Thnh Lm cng nhn thy: cc ch s khc v sinh ha nh Bilirubin huyt thanh, Albumin, globulin cc ch s Hng cu, Bch cu v Tiu cu u khng c s thay i sau iu tr [1]. Jung cng nhn xt: Protein, Albumin mu v Bilirubin khng thay i sau iu tr BDD [trch 2]. Chng ti khng nhn thy tc dng ph c ngha no trong qu trnh iu tr Fortec, 2 BN xut hin chng mt bun nn nhng tc dng ph ny mt i nhanh chng. Nghin cu ca Quch Thnh Lm v cc tc gi Hn Quc cng a ra nhn xt tng t [1.2.3]. Nghin cu trn 328 BN dng Fortec, cc tc gi nhn thy khng pht hin tc dng ph no, tr mt vi trng hp bun nn nh [trch 5] KT LUN: 4 tun iu tr bng fortec bnh nhn vim gan cho thy thuc c tc dng lm gim cc triu chng c nng nh: Mt mi, chn n, y chng bng, mt ng v au vng gan, ng thi thuc c tc dng lm gim mnh ALT v AST trong mu. 6

Ti liu tham kho 1.Quch Thanh Lm v cng s (2004): iu tr vim gan siu vi mn tnh vi Nissel kt qu theo di sau 1 nm. Y hc thnh ph H Ch Minh tp 8 ph bn s 1. trang 23-30. 2.Abdel-Salam OM, Sleem AA, Morsy FA et al (2007). Effects of biphenyldimethyldicarboxylate administration alone or combined with silymarin in the CCL4 model of liver fibrosis in rats.Scientific World Journal.;7:1242-55 3. Hyo-Suk Lee., Yong Tae Kim, Hyun Chaee Jung et al (1991), Prospective, randomized, control trial with Diphenyl dimethyl dicarboxylate in chronic active liver diseases: The effect on lowing serum, alanine aminotransferase level. The Korean journal of Internal Medicine, Vol 40, No 2, 1991,172-178. 4.Sawy SA, Shafey AM, Bahrawy HA et al (2002). Effect of dimethyl diphenyl bicarboxylate on normal and chemically-injured liver .East Mediterr Health J.8(1):95-104. 5. Gao M, Zhang J, Liu G et al (2005). Effect of diphenyl dimethyl bicarboxylate on concanavalin A-induced liver injury in mice. Liver Int. 25(4):904-12