Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine

J Hepatol. 2000 Feb;32(2):300-6. doi: 10.1016/s0168-8278(00)80076-8.


Background/aims: Interferon alpha provides benefit in only a limited number of patients with chronic anti-HBe-positive hepatitis B. The aim of this study was to verify the long-term efficacy of lamivudine treatment of these patients and the incidence of lamivudine-resistant hepatitis B virus mutants.

Methods: Fifteen consecutive patients with chronic anti-HBe-positive hepatitis B were treated with lamivudine 100 mg once daily for 52 weeks. Levels of alanine aminotransferase, HBV DNA, hepatitis B surface antigen, and IgM antibodies to hepatitis B core antigen were monitored during therapy and 12-month follow up. The polymerase gene was amplified by polymerase chain reaction and the region coding for YMDD amino acid motif was directly sequenced.

Results: Only 2/15 patients (13%) had a sustained virological and biochemical response and improved histologically. Eleven out of 15 (74%) showed inhibition of viral replication and normalization of alanine aminotransferase levels during lamivudine treatment but relapsed 1-12 months after terminating therapy. In the two remaining patients (13%), HBV DNA initially became negative but reappeared in the serum after 24 weeks, and in both patients the emergence of YMDD mutants was demonstrated.

Conclusions: Our data confirm the antiviral efficacy of lamivudine in anti-HBe-positive patients, but response to a 1-year course was only transient as the majority of patients relapsed after therapy withdrawal. The lack of a sustained effect and the emergence of lamivudine-resistant mutants suggest that therapy for chronic hepatitis B should be based on a combination of several therapeutic agents.

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Amino Acid Sequence / genetics
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Antibodies, Viral / analysis*
  • DNA, Viral / analysis*
  • DNA-Directed DNA Polymerase / genetics
  • Female
  • Follow-Up Studies
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology*
  • Humans
  • Immunoglobulin M / analysis
  • Immunoglobulin M / immunology
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Liver / pathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Molecular Sequence Data


  • Anti-HIV Agents
  • Antibodies, Viral
  • DNA, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Immunoglobulin M
  • Lamivudine
  • Alanine Transaminase
  • DNA-Directed DNA Polymerase