Fabrizi Fabrizio, Dulai Gareth, Dixit Vivek, Bunnapradist Suphamai, Martin Paul
Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Transplantation. 2004 Mar 27;77(6):859-64. doi: 10.1097/01.tp.0000116448.97841.6d.
Numerous reports have appeared on lamivudine use for the treatment of hepatitis B virus (HBV) infection after renal transplantation (RT). However, the efficacy and safety of lamivudine after RT remain unclear.
The authors evaluated the efficacy and safety of initial lamivudine monotherapy in RT recipients with hepatitis B by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcomes were hepatitis B (HB) e antigen (Ag) and HBV-DNA clearance (as measures of efficacy); the secondary outcomes were biochemical response (as measures of efficacy), dropout rate, and lamivudine resistance (as measures of tolerability). The authors used the random effects model of DerSimonian and Laird, and outcomes were analyzed on an intent-to-treat basis.
The authors identified 14 clinical trials (184 patients); all of these were prospective cohort studies. The mean overall estimate for HBV-DNA and HBeAg clearance, alanine aminotransferase normalization, and lamivudine resistance was 91% (95% confidence interval [CI], 86%-96%), 27% (95% CI, 16%-39%), 81% (95% CI, 70%-92%), and 18% (95% CI, 10%-37%), respectively. HBeAg seroconversion rate was assessed in four (28%) trials and ranged between 0% and 46%. The P value was greater than 0.05 for our test of study homogeneity. There was no association between rate of patients who were male patients or had cirrhosis, race, age, lamivudine dose, and HBV-DNA or HBeAg clearance. Increased duration of lamivudine therapy was positively associated with frequency of HBeAg loss (r =0.51, P =0.039) and lamivudine resistance (r =0.620, P =0.019). Only 2 (14%) of 14 studies reported a dropout rate greater than 0%.
Our meta-analysis showed that the majority of RT recipients with hepatitis B had high virologic and biochemical response with lamivudine. Tolerance to lamivudine was good. However, lamivudine resistance was frequent with prolonged therapy, potentially limiting its long-term efficacy after RT.
已有大量关于肾移植（RT）后使用拉米夫定治疗乙型肝炎病毒（HBV）感染的报道。然而，RT后拉米夫定的疗效和安全性仍不明确。
作者通过对文献进行系统回顾并对临床试验进行荟萃分析，评估了拉米夫定初始单药治疗对RT合并乙型肝炎患者的疗效和安全性。主要结局为乙肝（HB）e抗原（Ag）和HBV-DNA清除（作为疗效指标）；次要结局为生化反应（作为疗效指标）、脱落率和拉米夫定耐药性（作为耐受性指标）。作者采用DerSimonian和Laird随机效应模型，并在意向性治疗基础上分析结局。
作者确定了14项临床试验（184例患者）；所有这些均为前瞻性队列研究。HBV-DNA和HBeAg清除、丙氨酸氨基转移酶正常化以及拉米夫定耐药性的总体平均估计值分别为91%（95%置信区间[CI]，86%-96%）、27%（95%CI，16%-39%）、81%（95%CI，70%-92%）和18%（95%CI，10%-37%）。在四项（28%）试验中评估了HBeAg血清学转换率，范围在0%至46%之间。我们的研究同质性检验P值大于0.05。男性患者或患有肝硬化、种族、年龄、拉米夫定剂量与HBV-DNA或HBeAg清除率之间无关联。拉米夫定治疗时间延长与HBeAg丢失频率（r =0.51，P =0.039）和拉米夫定耐药性（r =0.620，P =0.019）呈正相关。14项研究中只有2项（14%）报告脱落率大于0%。
我们的荟萃分析表明，大多数RT合并乙型肝炎的患者使用拉米夫定后有较高的病毒学和生化反应。对拉米夫定的耐受性良好。然而，长期治疗时拉米夫定耐药很常见，这可能会限制其在RT后的长期疗效。
