Journal
JOURNAL OF HEPATOLOGY
Volume 32, Issue 2, Pages 300-306Publisher
ELSEVIER
DOI: 10.1016/S0168-8278(00)80076-8
Keywords
anti-HBe positive chronic hepatitis B; antiviral therapy; lamivudine; lamivudine-resistant mutants
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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 mere 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-gear 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.
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