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

• Published in: Journal of gastroenterology and hepatology Vol. 21; no. 4; pp. 657 - 663
• Main Authors: Canbakan, Billur, Senturk, Hakan, Tabak, Fehmi, Akdogan, Meral, Tahan, Veysel, Mert, Ali, Sut, Necdet, Ozaras, Resat, Midilli, Kenan, Ozbay, Gulsen
• Format: Journal Article
• Language: English
• Published: Australia 01-04-2006
• Subjects: Adult; Aged; Anti-HIV Agents - administration & dosage; Drug Combinations; Female; Hepatitis D, Chronic - drug therapy; Hepatitis D, Chronic - pathology; Humans; Interferon-alpha - administration & dosage; Lamivudine - administration & dosage; Male; Middle Aged; Recombinant Proteins; Treatment Outcome
• ISSN: 0815-9319
• DOI: 10.1111/j.1440-1746.2006.04082.x

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.
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.
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).
Interferon and lamivudine in combination is an encouraging treatment method and may be superior to IFN alone in chronic delta hepatitis.