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

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.