Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFN alpha) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFN alpha-2a 180 mu g weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFN alpha alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. RESULTS: The mean age of the patients was 26.7 +/- 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFN alpha alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFN alpha-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. CONCLUSION: Administration of PEG-IFN alpha-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.