High rates of progressive hepatic functional deterioration whether lamivudine therapy is continued or discontinued after emergence of a lamivudine-resistant mutant: a prospective randomized controlled study

J Gastroenterol. 2006 Mar;41(3):240-9. doi: 10.1007/s00535-005-1750-5.

Abstract

Background: The management of patients with lamivudine-resistant mutants remains challenging, and no clear evidence has been presented concerning the discontinuation of lamivudine.

Methods: Seventy-four patients with lamivudine-resistant mutants were prospectively enrolled and randomized; 37 patients continued (group A) and 37 patients discontinued lamivudine therapy (group B). The median follow-up was 20 months.

Results: Serum albumin levels were reduced and prothrombin time was prolonged in both groups versus baseline (P = 0.015 and 0.045, respectively). Four patients in group A (10.8%) and six in group B (16.2%) experienced hepatitis flare, but the difference was not significant (P > 0.05). Multivariate analyses identified a younger age as a risk factor for hepatitis flare (P = 0.021). Seven (18.9%) decompensations occurred in group A and five (13.5%) in group B, which was not a significant difference (P > 0.05). Multivariate analyses revealed higher alanine aminotransferase and a lower platelet count as risk factors for hepatic decompensation (P = 0.001 and 0.001, respectively). The patients whose platelet count was <65 000/microl experienced hepatic decompensations more frequently (50%) than those with platelet counts >65 000/microl (13.2%) during follow-up (P = 0.05).

Conclusions: The clinical course of group B was not significantly different from that of group A. Therefore, the discontinuation of lamivudine may be a feasible option when other antiviral agents active against lamivudine-resistant mutants are unavailable.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Alanine Transaminase / drug effects
  • Bilirubin / blood
  • Biomarkers / blood
  • DNA, Viral / blood
  • DNA, Viral / drug effects
  • Disease Progression
  • Drug Resistance, Viral / drug effects*
  • Female
  • Follow-Up Studies
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / drug effects
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / metabolism
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / epidemiology
  • Hepatitis B, Chronic / virology
  • Humans
  • Korea / epidemiology
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Liver Failure / blood
  • Liver Failure / epidemiology*
  • Liver Failure / physiopathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation / drug effects*
  • Platelet Count
  • Predictive Value of Tests
  • Prospective Studies
  • Prothrombin Time
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Risk Factors
  • Serum Albumin / drug effects
  • Serum Albumin / metabolism

Substances

  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Reverse Transcriptase Inhibitors
  • Serum Albumin
  • Lamivudine
  • Alanine Transaminase
  • Bilirubin