Efficacy of interferon alpha-2b and lamivudine combination treatment in comparison to interferon alpha-2b alone in chronic delta hepatitis: A randomized trial

Background and aim Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN-alpha 2b and lamivudine combination treatment in comparison to IFN-alpha 2b alone in patients with chronic delta hepatitis. Methods Twenty-six patients with chronic delta hepatitis were randomized into two groups. Twelve patients received IFN-alpha 2b alone (eight men, four women; mean +/- SD age: 43.83 +/- 8.57 years), and 14 patients received IFN-alpha 2b plus lamivudine combination (seven men, seven women; mean +/- SD age: 42.5 +/- 11.02 years). The dose of IFN-alpha 2b was 10 MU t.i.w. and of lamivudine was 100 mg/day. The groups were comparable in reference to serum alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, albumin levels, histological activity and stage. Four patients (33.3%) in the IFN group and two (14.3%) in the combination group had cirrhosis (P = 0.2). The duration of treatment was 48 weeks with an untreated follow-up period of at least 96 weeks (mean +/- SD, 3.1 +/- 1.9 years). A liver biopsy was performed at the end of treatment. Results Eight patients from the IFN group and 11 from the combination group completed treatment. Serum ALT values became normal in 8/14 patients (57.1%) treated with IFN plus lamivudine and in 5/12 patients (41.7%) treated with IFN alone (P = 0.43). Serum hepatitis delta virus RNA was no longer detectable in nine of 14 (64.3%) patients treated with IFN plus lamivudine as compared to five of 12 (41.6%) patients treated with IFN alone (P = 0.024). In both groups female patients had significantly better virological response rate (P = 0.007). There was a significant improvement in histological activity in the combination group (mean decrease 5.27 +/- 1.08 score, P = 0.001), but not in the IFN group (mean decrease 1.44 +/- 1.59 score, P = 0.39). No significant improvement was observed in regards to fibrosis. Four of the 14 patients (28.6%) treated with combination therapy as compared to two of 12 patients treated with IFN (16.7%) were sustained virological responders (P = 0.47). The 5-year survival rate was 65% in the IFN group and 85% in the combination group (P > 0.05). Conclusion Interferon and lamivudine in combination is an encouraging treatment method and may be superior to IFN alone in chronic delta hepatitis.