Author information

• ¹Institute for Virology, Medical Faculty of the University of Duisburg-Essen, Essen, Germany.
• ²Institutul de Boli Infectioase, Bucharest, Romania.
• ³Spitalul Clinic de Boli Infectioase si, Timisoara, Romania.
• ⁴Dicle University Medical Faculty, Diyarbakir, Turkey.
• ⁵Ege University Medical Faculty, Izmir, Turkey.
• ⁶Uludag University Medical Faculty, Bursa, Turkey.
• ⁷Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
• ⁸Heinrich Heine University, Dusseldorf, Germany.
• ⁹Petrus Hospital, Wuppertal, Germany.
• ¹⁰Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg, Brandenburg Medical School (Theodor Fontane), Brandenburg, Germany.
• ¹¹Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Potsdam, Germany.
• ¹²Medical School, National and Kapodistrian University of Athens, Athens, Greece.
• ¹³Ankara University Medical School, Ankara, Turkey.
• ¹⁴Hannover Medical School, Hannover, Germany.
• ¹⁵Orgenesis, Inc, Germantown, Maryland, USA.
• ¹⁶German Centre for Infection Research (DZIF), HepNet Study-House/German Liver Foundation, Hannover, Germany.
• ¹⁷D-SOLVE Consortium an EU Horizon Europe funded project (No 101057917), Hannover, Germany.
• ¹⁸University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
• ¹⁹German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, Germany.
• ²⁰Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey.

Abstract

Background & aims: Until 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.

Methods: In 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).

Results: Until 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]).

Conclusions: Liver-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.