Katz L H, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R
Department of Medicine D and Liver Institute, Beilinson Campus, Rabin Medical Center, Petah-Tiqva, Israel.
J Viral Hepat. 2008 Feb;15(2):89-102. doi: 10.1111/j.1365-2893.2007.00902.x.
To assess the effects of prophylactic lamivudine on reactivation and mortality following immunosuppressive therapy in hepatitis B surface antigen (HBsAg)-positive patients, we performed a meta-analysis. Systematic review and meta-analysis of randomized and nonrandomized prospective controlled trials and retrospective comparative case series were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. The primary outcomes were virological reactivation, clinical reactivation and mortality. Secondary outcomes included hepatitis B virus (HBV)-related mortality, liver histology, discontinuation or disruption of immunosuppressive therapy, lamivudine-resistant HBV strains and adverse events. A total of 21 studies were included, two of which were randomized controlled trials. Clinical and virological reactivation were significantly reduced in the lamivudine group [odds ratio (OR) 0.09; 95% confidence interval (CI) 0.05-0.15 and OR 0.04; 95% CI 0.01-0.14 respectively]. All-cause mortality was significantly reduced in the lamivudine group (OR 0.36; 95% CI 0.23-0.56) which translates to only 11 patients who need to be treated to prevent one death. Lamivudine significantly reduced HBV-related mortality, and discontinuations or disruptions of the immunosuppressive treatment. No adverse effects of lamivudine were recorded, and resistance to lamivudine occurred in low rates. We demonstrated a clear benefit of lamivudine in terms of clinical and virological HBV reactivation, overall mortality, HBV-related mortality and interruptions or discontinuations in the immunosuppressive treatment. Lamivudine should be administered prophylactically to HBsAg-positive patients who are about to receive immunosuppressive therapy.
为评估预防性使用拉米夫定对乙型肝炎表面抗原（HBsAg）阳性患者免疫抑制治疗后病毒激活及死亡率的影响，我们进行了一项荟萃分析。通过Cochrane肝胆疾病组对照试验注册库、Cochrane对照试验中央注册库、MEDLINE、EMBASE和LILACS，检索随机和非随机前瞻性对照试验以及回顾性比较病例系列的系统评价和荟萃分析。主要结局为病毒学激活、临床激活和死亡率。次要结局包括乙型肝炎病毒（HBV）相关死亡率、肝脏组织学、免疫抑制治疗的中断或终止、拉米夫定耐药HBV毒株及不良事件。共纳入21项研究，其中两项为随机对照试验。拉米夫定组的临床和病毒学激活显著降低[比值比（OR）0.09；95%置信区间（CI）0.05 - 0.15和OR 0.04；95% CI 0.01 - 0.14]。拉米夫定组的全因死亡率显著降低（OR 0.36；95% CI 0.23 - 0.56），这意味着每预防1例死亡仅需治疗11例患者。拉米夫定显著降低了HBV相关死亡率以及免疫抑制治疗的中断或终止。未记录到拉米夫定的不良反应，且拉米夫定耐药发生率较低。我们证明了拉米夫定在临床和病毒学HBV激活、总体死亡率、HBV相关死亡率以及免疫抑制治疗的中断或终止方面具有明显益处。对于即将接受免疫抑制治疗的HBsAg阳性患者，应预防性使用拉米夫定。
