Five‐year follow‐up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D

Abstract

AbstractBackground & AimsUntil recently, pegylated interferon‐alfa‐2a (PEG‐IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG‐IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short‐term relapses within 24 weeks. The virological and clinical long‐term effects after prolonged PEG‐IFNa‐based treatment of hepatitis D are unknown.MethodsIn the HIDIT‐II study patients (including 40% with liver cirrhosis) received 180 μg PEG‐IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 μg PEG‐IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy).ResultsUntil the end of follow‐up, 16 (13%) patients developed liver‐related complications (PEG‐IFNa + TDF, n = 5 vs PEG‐IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long‐term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG‐IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG‐IFNa (16/102, p > .999) but was associated with a higher chance of HDV‐RNA suppression (p = .024, odds ratio 3.9 [1.3–12]).ConclusionsLiver‐related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG‐IFNa treatment. PEG‐IFNa treatment should be recommended to HDV‐infected patients until alternative therapies become available. Retreatment with PEG‐IFNa should be considered for patients with inadequate response to the first course of treatment.Clinical Trial registration: NCT00932971.