Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study

Background/Aims: In this study, lamivudine-interferon (LAM/IFN) combination therapy was compared to LAM monotherapy to verify if the combination treatment might improve efficacy and reduce the emergence of LAM-resistant mutants. Methods: Fifty patients with anti-HBe-positive chronic hepatitis B were treated for 12 months with LAM at 100 mg/day (26 pts) or with IFN at 5 MU t.i.w. + LAM 100 mg/day (24 pts). Serum ALT, HBV DNA and IgM anti-HBc were monitored during treatment and a 6-month follow-up. The polymerase gene was amplified by PCR and the region coding for YMDD motif was directly sequenced. Results: All patients normalized ALT and cleared HBV DNA during treatment. The response was maintained until the end of therapy in the LAM/IFN group, while in 5/26 initial responders treated with LAM alone, a virological and biochemical breakthrough was observed after 6-10 months, and selection for YMDD variants resulted. After therapy discontinuation, most patients relapsed; the response rate after 6 months was 17% in the LAM/IFN group and 19% in the LAM group. Conclusions: In anti-HBe-positive chronic hepatitis B, a 12-month course of LAM/IFN combination therapy is as beneficial as LAM monotherapy, however, the combination regimen appeared to prevent or delay the emergence of YMDD variants. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.