A 12-month course of combination therapy with interferon-alfa and lamivudine in patients with chronic hepatitis delta virus: A single-center, prospective, open-label, uncontrolled study

Background: Chronic hepatitis delta virus (HDV) is a severe and rapidly progressive liver disease for which no therapy has been proved to be effective. Objective: The aim of this study was to investigate the efficacy and tolerability of long-term therapy with a combination of recombinant interferon (IFN)-alfa. and lamivudine. Methods: In this single-center, prospective, open-label, uncontrolled study, patients aged 18 to 60 years with chronic HDV were eligible. Patients were treated with a combination of 10 million units of IFN-alfa-2b subcutaneously 3 times weekly and lamivudine 100 mg once daily for 12 months. The primary outcome measures were biochemical and histologic response at the end of treatment and at least 12 months thereafter. Results: Twelve patients (10 men, 2 women; mean age, 33.9 years [range, 19-49 years]) were enrolled (6 treatment-naive patients, 6 previously treated patients). Normalization or decrease of >50% from baseline in serum alanine aminotransferase (ALT) level occurred in 8 (66.7%) of 12 patients at month 12 of treatment. Of the 12 patients, 10 (83.3%) completed the trial; 1 (8.3%) was withdrawn because of severe leukopenia. and 1 (8.3%) was lost to follow-up. Relapses occurred in 5 of 8 (63.3%) initial responders shortly after the cessation of therapy. In 3 (25%) patients whose ALT levels became normal at the end of the therapy, the complete biochemical responses persisted for up to 3 years (mean, 31 months). The treatment was associated with a marked improvement in histologic activity. Conclusions: In this study, combination therapy with IFN-alfa and lamivudine was well tolerated and reduced hepatic inflammation was found. Further controlled trials are needed to show possible beneficial effects of this model of therapy and to determine the optimal dose and duration of therapy for chronic HDV.