Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials

Transplantation. 2004 Mar 27;77(6):859-64. doi: 10.1097/01.tp.0000116448.97841.6d.

Abstract

Background: 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.

Methods: 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.

Results: 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%.

Conclusions: 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • DNA, Viral / analysis
  • Hepatitis B / drug therapy*
  • Humans
  • Kidney Transplantation / adverse effects*
  • Lamivudine / therapeutic use*
  • MEDLINE
  • Postoperative Complications / drug therapy
  • Postoperative Complications / virology*

Substances

  • DNA, Viral
  • Lamivudine