Browsing by Author "Idilman, Ramazan"
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Item Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): A randomised, placebo controlled, phase 2 trial(Elsevier, 2019-03) Wedemeyer, Heiner; Yurdaydin, Cihan; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George V.; Keskin, Onur; Port, Kerstin; Radu, Monica; Celen, Mustafa K.; Idilman, Ramazan; Weber, Kristina; Stift, Judith; Wittkop, Ulrike; Heidrich, Benjamin; Zeuzem, Stefan; Gürel, Selim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; 7003706434Abstract Background Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. Methods We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per mu L, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 mu g of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. Findings Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1.84, 95% CI 0.86-3.91, p=0.12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. Interpretation Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D.Publication Residual low hdv viremia is associated with hdv rna relapse after peg-ifna-based antiviral treatment of hepatitis d (delta): Results from the hidit-ii study(Elsevier, 2020-08-01) Bremer, Birgit; Anastasiou, Olympia; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Akarca, Ulus S.; Idilman, Ramazan; Zeuzem, Stefan; Erhardt, Andreas; Lueth, Stefan; Papatheodoridis, George; Radu, Monica; Manns, Michael P.; Cornberg, Markus; Yurdaydın, Cihan; Wedemeyer, Heiner; Gürel, Selim; GÜREL, SELİM; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; HLH-8209-2023Item Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta(Wiley, 2020-07-24) Wranke, Anika; Hardtke, Svenja; Heidrich, Benjamin; Dalekos, George; Yalçın, Kendal; Tabak, Fehmi; Çakaloğlu, Yılmaz; Akarca, Ulus S.; Lammert, Frank; Haeussinger, Dieter; Mueller, Tobias; Woebse, Michael; Manns, Michael P.; Idilman, Ramazan; Cornberg, Markus; Wedemeyer, Heiner; Yurdaydın, Cihan; Gürel, Selim; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; EYK-5719-2022; 7003706434Hepatitis 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 alpha-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 End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated 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 retreated 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 nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic 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.