Elsevier

Journal of Hepatology

Volume 32, Issue 2, February 2000, Pages 300-306
Journal of Hepatology

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

https://doi.org/10.1016/S0168-8278(00)80076-8Get rights and content

Abstract

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.

Section snippets

Patients

Fifteen consecutive chronic HBsAg carriers (11 male and 4 female, mean age=42.4 years, range 25–63 years) with a median duration of HBV infection of 6 years (range 4–15 years) and anti-HBe-positive chronic hepatitis B were included in the study and treated with lamivudine (Glaxo-Wellcome) 100 mg once daily for 52 weeks. All patients were followed for at least 12 months (range 12–30 months) after lamivudine discontinuation. Nine patients had previously been treated with IFN: four showed a

Results

In 15 patients with anti-HBe-positive chronic hepatitis B treated with 100 mg of lamivudine daily for 52 weeks, three types of response were observed.

Discussion

As with HBeAg-positive chronic hepatitis B patients, the results obtained in this study confirm the strong antiviral activity of lamivudine also in patients with the anti-HBe-positive form. In fact, oral administration of lamivudine at 100 mg daily induced a rapid and marked reduction of HBV DNA levels, which became undetectable after 8 weeks of therapy in all 15 patients including the five patients with no response to a previous IFN treatment. Following the inhibition of viral replication, a

Acknowledgements

The authors are grateful to Ms Paulene Butts for her assistance in the preparation of the manuscript.

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