Bain V G, Kneteman N M, Ma M M, Gutfreund K, Shapiro J A, Fischer K, Tipples G, Lee H, Jewell L D, Tyrrell D L
Department of Medicine, University of Alberta, Edmonton, Canada.
Transplantation. 1996 Nov 27;62(10):1456-62. doi: 10.1097/00007890-199611270-00013.
Liver transplantation for endstage hepatitis B virus (HBV) infection has been associated with survival inferior to that of liver transplantation in other chronic liver diseases due to HBV reinfection of the graft. Lamivudine is a new nucleoside analog with potent antiviral effects against hepatitis B. Our aim was to test its efficacy when used pre- and posttransplantation in HBV-DNA positive patients with endstage liver disease. Patients received oral lamivudine 100 mg daily both pretransplant and posttransplant. Viral serology, serum and tissue HBV-DNA and liver histology were assessed sequentially. Five consecutive patients with endstage hepatitis B were entered into the trial. Serum HBV-DNA was cleared pretransplant in all patients. Three of four transplanted patients cleared HBeAg and HBsAg postoperatively, whereas all four became negative for serum HBV-DNA (dot-blot and PCR). Liver biopsies were negative for HBV-DNA by PCR in 3 of 4 cases. Lymphocytes were negative for HBV-DNA by PCR in all cases. With follow-up of 3, 14, 16, and 26 months, two patients have normal liver enzymes and normal liver histology and two have developed recurrent hepatitis B. No significant side effects were seen. This pilot study shows that lamivudine can effectively inhibit hepatitis B virus in cirrhotic patients pretransplant and posttransplant. A lamivudine resistant mutant developed in two patients. Transplant recipients with actively replicating HBV related cirrhosis may achieve a good outcome after liver transplantation using lamivudine, but viral resistance is likely to be a significant problem.
因移植物乙型肝炎病毒（HBV）再感染，晚期HBV感染患者的肝移植生存率低于其他慢性肝病患者的肝移植生存率。拉米夫定是一种新型核苷类似物，对乙型肝炎具有强大的抗病毒作用。我们的目的是测试其在晚期肝病HBV-DNA阳性患者移植前后使用时的疗效。患者在移植前和移植后均每日口服100mg拉米夫定。依次评估病毒血清学、血清和组织HBV-DNA以及肝脏组织学。连续5例晚期乙型肝炎患者进入该试验。所有患者移植前血清HBV-DNA均被清除。4例移植患者中有3例术后HBeAg和HBsAg清除，而所有4例血清HBV-DNA（斑点印迹法和PCR）均转为阴性。4例中有3例肝活检经PCR检测HBV-DNA为阴性。所有病例淋巴细胞经PCR检测HBV-DNA均为阴性。随访3、14、16和26个月，2例患者肝酶正常且肝脏组织学正常，2例发生复发性乙型肝炎。未观察到明显副作用。这项初步研究表明，拉米夫定可有效抑制肝硬化患者移植前后的乙型肝炎病毒。2例患者出现拉米夫定耐药突变体。对于有活跃复制的HBV相关肝硬化的移植受者，使用拉米夫定进行肝移植后可能会取得良好疗效，但病毒耐药可能是一个重大问题。
