Yazar "Hardtke, Svenja" seçeneğine göre listele
Listeleniyor 1 - 7 / 7
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe Frequency, severity and impact of Peg-IFNa-associated flares in HDV infection: Results from the HIDIT-II study(Elsevier, 2019) Hardtke, Svenja; Wedemeyer, Heiner; Caruntu, Florin Alexandru; Curescu, Manuela; Kendal, Yalcin; Akarca, Ulus; Yurdcu, Esra[Abstract Not Available]Öğe Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial(Elsevier Sci Ltd, 2019) Wedemeyer, Heiner; Yurdaydin, Cihan; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.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. Copyright (c) 2019 Elsevier Ltd. All rights reserved.Öğe Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial(Wiley, 2023) Dinkelborg, Katja; Kahlhöfer, Julia; Dörge, Petra; Yurdaydın, Cihan; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalçın, KendalBackground & AimsInfection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. MethodsHere, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. ResultsOverall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL. ConclusionsOverall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.Öğe Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-II study(Wiley, 2020) Bremer, Birgit; Anastasiou, Olympia E.; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalçın, Kendal; Akarca, Ulus S.; Gürel, Selim; Zeuzem, Stefan; Erhardt, Andreas; Luth, Stefan; Papatheodoridis, George, V.; Radu, Monica; Idilman, Ramazan; Manns, Michael P.; Cornberg, Markus; Yurdaydın, Cihan; Wedemeyer, HeinerThe role of low levels of HDV-RNA during and after interferon therapy of hepatitis D is unknown. We re-analysed HDV RNA in 372 samples collected in the HIDIT-2 trial (Wedemeyer et al, Lancet Infectious Diseases 2019) with the Robogene assay (RA; Jena Analytics). Data were compared with the previously reported in-house assay (IA). We detected HDV-RNA in one-third of samples previously classified as undetectable using the highly sensitive RA. Low HDV viraemia detectable at week 48 or week 96 was associated with a high risk for post-treatment relapse, defined as HDV RNA positivity in both assays at week 120. HDV RNA relapses occurred in 10/15 (67%) patients with detectable low HDV RNA at week 48 and in 10/13 (77%) patients with low viraemia samples at week 96. In contrast, the post-treatment relapse rate was lower in patients with undetectable HDV RNA in both assays during treatment.Öğe 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) Bremer, Birgit; Anastasiou, Olympia; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Akarca, Ulus S.[Abstract Not Available]Öğe Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta(Wiley, 2020) Wranke, Anika; Hardtke, Svenja; Heidrich, Benjamin; Dalekos, George; Yalçın, Kendal; Tabak, Fehmi; Gürel, Selim; Çakaloglu, Yılmaz; Akarca, Ulus S.; Lammert, Frank; Haeussinger, Dieter; Mueller, Tobias; Woebse, Michael; Manns, Michael P.; İdilman, Ramazan; Cornberg, Markus; Wedemeyer, Heiner; Yurdaydın, CihanHepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFN alpha-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-IFN alpha-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFN alpha-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-IFN alpha-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-IFN alpha-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-IFN alpha-2a treatment leads to improved clinical long-term outcome.Öğe A transient early HBV-DNA increase during PEG-IFN? therapy of hepatitis D indicates loss of infected cells and is associated with HDV-RNA and HBsAg reduction(Wiley, 2021) Anastasiou, Olympia E.; Yurdaydin, Cihan; Maasoumy, Benjamin; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, KendalHBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFN alpha on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFN alpha-2a plus tenofovir-disoproxil-fumarate (PEG-IFN alpha/TDF, n = 59) or placebo (PEG-IFN alpha/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFN alpha/PBO-treated patients but also in 76% of PEG-IFN alpha/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFN alpha/TDF-treated and 12 PEG-IFN alpha/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFN alpha-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFN alpha-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss.
