拉咪呋啶预防乙肝相关性肝硬化肝移植术后乙肝再感染的临床对照研究  

Effect of lamivudine against HBV reinfection after liver transplantation

作　　者：卢实春[1] 严律南[1] 李波[1] 文天夫[1] 赵纪春[1] 程南生[1] 刘冲[2] 刘隽[1] 王晓波[1] 李晓东[1] 秦山[2] 赵连三[2] 雷秉均[2] 张秀辉[3] 

机构地区：[1]四川大学华西医院普外科,四川省成都市610041 [2]四川大学华西医院肝炎研究室,四川省成都市610041 [3]四川大学华西医院病理教研室,四川省成都市610041

出　　处：《世界华人消化杂志》2003年第2期185-190,共6页World Chinese Journal of Digestology

基　　金：四川省科技厅资助项目;No.C2005~~

摘　　要：目的:了解乙肝相关性失代偿肝硬化肝移植术后使用拉咪呋啶预防移植物乙肝再感染的疗效及乙肝标志物在血清及肝组织中的动态变化.方法:用酶联放免法,血清HBVDNA荧光定量法、肝穿组织免疫组化LSAB法及HBVDNA原位杂交法定期检测25例受体血清及肝穿组织,观察肝移植术后HBV标志物在血清及肝组织中的动态变化.本研究设计为前瞻的开放的非随机的临床对照研究.25例被分为乙肝病毒活跃复制(15例)及非活跃复制组(10例)两组,皆以拉咪呋啶100mg/d术前后服用预防,非活跃复制组中有3例未能及时服用拉咪呋啶作为对照组.结果:在HBV活跃复制组,术前口服拉咪呋啶平均2wk能使80%以上的患者血清HBVDNA阴转;继续口服,术后表面抗原消失,部分血清乙肝病毒抗体(表面抗体HBsAb9/15,核心抗体HBcAb13/15及HBeAb11/15)可在术后1-2wk出现,至6mo可逐渐消失;血清中HBVDNA荧光定量可一直维持阴转的状态;肝穿组织中HbsAg,HBcAg及HBVDNA原位杂交可长期维持阴性.10例乙肝病毒活跃复制受体其HBV血清标志物在12-44wk之间完全消失;本组中2例(2/15,13.3%)在2a时发生拉咪呋啶预防失败而致移植物再感染或乙肝复发;在HBV非活跃复制组,乙肝病毒抗原抗体表达同活跃复制组:表面抗原术后即消失,乙肝病毒抗体即在1-2wk出现(BsAb4/7,HBcAb6/7,HBeAb2/7),6mo左右消失.3例(43%,3/7)在近2a时血清及肝组织中HBV标志即完全消失.本组无移植物再感染,乙型肝炎复发及乙肝病毒相关死亡.若血清中重新出现表面抗原或HBVDNA荧光定量阳性或肝穿组织免疫组化或HBVDNA原位杂交阳性则可诊断为HBV再感染.未能及时服用拉咪呋啶的3例非活跃复制的乙肝受体分别在术后8、10、12mo移植物感染及复发新肝乙型肝炎,移植物再感染率及乙肝复发率为100%,其中1例死于纤维淤胆性肝炎,后二者经加用拉咪呋啶治疗为主的综合治疗而缓解.本研究除对照组�AIM:To assess the prophylactic effect of lamivudine in preventing reinfection of HBV and the dynamic alternations of HBV markers in serum and liver tissue after liver transplantation. METHODS:Twenty five recipients were non-randomly divided into HBV active replicating group (15 cases) and HBV non-active replicating group (10 cases) and control group (3 cases). Lamivudine 100 mg /day was administered to each patient before and after operation, 3 of 10 cases in non-active replicating group failed to take lamivudine on time and thus was grouped as control.The HBV markers in serum and bioptic liver tissues in 25 recipients were evaluated regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative assay, immunohistochemistry stain LSAB and digoxin labeled HBV DNA hybridization in situ. RESULTS:Serum HBV DNA in 80 % cases with active HBVreplication became negative following 2-week periods of lamivudine treatment prior to liver transplantation.HBsAg in all recipients converted to negative after liver transplantation. HBsAb (9/15), HbcAb(13/15) and HBeAb (11/15) appeared within one week postoperatively, and disappeared gradually within 6 months.Serum HBV DNA was negative;Results of in situ hybridization in bioptic liver tissue showed that HBsAg, HBcAg as well as HBV DNA remained negative after treatment of lamivudine. 10 of 15 recipients had got to clinical clearance of HBV, HBV markers were undetectable in both serum and liver biopsy samples between 12 to 44 weeks (average 24 weeks), 1-, 2-year survival rate in this group reached 83 %. Two of 15 subjects (13.3 %) developed allograft HBV reinfection or recurrence of hepatitis in 2 years after the prophylactic treatment of lamivudine.In HBV non-active replicating group, the outcome was similar with that in the active group. The HBV antibody was HBsAb (+, 4/7), HBcAb (+, 6/7), HBeAb (+, 2/7), 3 of 7 recipients achieved HBV clinical clearance in both serum and liver bioptic samples, while in control group, all 3 recipients developed allograft HBV reinfec

关 键 词：拉咪呋啶 预防 乙肝相关性肝硬化 肝移植术 乙肝再感染 临床对照研究 

分 类 号：R657.3[医药卫生—外科学]