Anika Wranke1, Svenja Hardtke12, Benjamin Heidrich12, George Dalekos3, Kendal Yalcin4, Fehmi Tabak5, Selim Gurel6, Yilmaz Cakaloglu7, Ulus S Akarca8, Frank Lammert9, Dieter Häussinger10, Tobias Müller11, Michael Wöbse1, Michael P Manns12, Ramazan Idilman12, Markus Cornberg12, Heiner Wedemeyer213, Cihan Yurdaydin1214
1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.
2German Center for Infection Research (DZIF), Partner Site HepNet Study-House, Hannover, Germany.
3Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
4Dicle University Medical Faculty, Diyarbakir, Turkey.
5Department of Infectious Diseases, Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey.
6Uludag University Medical School, Bursa, Turkey.
7Memorial Hospital, Istanbul, Turkey.
8Ege University Medical Faculty, Izmir, Turkey.
9Department of Medicine II, Saarland University Medical Center, Saarland University, 66421, Homburg, Germany.
10Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University, Düsseldorf, Germany.
11Charite University, Berlin, Germany.
12Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey.
13Department of Gastroenterology and Hepatology, Essen University Hospital, Medical Faculty of the University Duisburg-Essen, Essen, Germany.
14Department of Gastroenterology and Hepatology, Koc University Medical School, Istanbul, Turkey.
Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48 weeks of pegylated interferon alfa-2a therapy.We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48 weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II), or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child Pugh scores B or C or an increase in Model for Endstage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were re-treated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n=19), Group II (n=20), Group III (n=21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were re-treated with IFN-based therapy: 42% (n=8) in PEG-IFNα-2a arms and 58% (n=11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with non-response to therapy and baseline cirrhosis. The annual event free survival rate in patients with cirrhosis vs non-cirrhotic patients at year 5 and 10 was 70% vs. 91% and 35% vs. 76%.Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.