TY - JOUR A1 - Heidrich, Benjamin A1 - Wiegand, Steffen B. A1 - Buggisch, Peter A1 - Hinrichsen, Holger A1 - Link, Ralph A1 - Möller, Bernd A1 - Böker, Klaus H. W. A1 - Teuber, Gerlinde A1 - Klinker, Hartwig A1 - Zehnter, Elmar A1 - Naumann, Uwe A1 - Busch, Heiner W. A1 - Maasoumy, Benjamin A1 - Baum, Undine A1 - Hardtke, Svenja A1 - Manns, Michael P. A1 - Wedemeyer, Heiner A1 - Petersen, Jörg A1 - Cornberg, Markus T1 - Treatment of Naive Patients with Chronic Hepatitis C Genotypes 2 and 3 with Pegylated Interferon Alpha and Ribavirin in a Real World Setting: Relevance for the New Era of DAA JF - PLOS ONE N2 - Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10-20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61%, GT3 47%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96%, GT3 90%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN +/- sofosbuvir/RBV in well-selected naive G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources. KW - peginterferon alpha-2B KW - HCV genotype-2 KW - sofosbuvir KW - infection KW - epidemology Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115149 SN - 1932-6203 VL - 9 IS - 10 ER - TY - JOUR A1 - Grammatikos, Georgios A1 - Lange, Christian A1 - Susser, Simon A1 - Schwendy, Susanne A1 - Dikopoulos, Nektarios A1 - Buggisch, Peter A1 - Encke, Jens A1 - Teuber, Gerlinde A1 - Goeser, Tobias A1 - Thimme, Robert A1 - Klinker, Hartwig A1 - Boecher, Wulf O. A1 - Schulte-Frohlinde, Ewert A1 - Penna-Martinez, Marissa A1 - Badenhoop, Klaus A1 - Zeuzem, Stefan A1 - Berg, Thomas A1 - Sarrazin, Christoph T1 - Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients JF - PLOS ONE N2 - Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-alpha and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients. KW - chronic Hepatitis C KW - sustained virological response KW - common genetic determinants KW - D serum-levels KW - IL28B polymorphisms KW - interferon alpha KW - viral clearance KW - virus infection KW - severe fibrosis KW - D insufficiency Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117310 SN - 1932-6203 VL - 9 IS - 2 ER - TY - JOUR A1 - Cornberg, Markus A1 - Stoehr, Albrecht A1 - Naumann, Uwe A1 - Teuber, Gerlinde A1 - Klinker, Hartwig A1 - Lutz, Thomas A1 - Möller, Hjördis A1 - Hidde, Dennis A1 - Lohmann, Kristina A1 - Simon, Karl-Georg T1 - Real-world safety, effectiveness, and patient-reported outcomes in patients with chronic hepatitis C virus infection treated with glecaprevir/pibrentasvir: updated data from the German Hepatitis C-Registry (DHC-R) JF - Viruses N2 - Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination. KW - direct-acting antiviral KW - glecaprevir/pibrentasvir KW - hepatitis C virus KW - real world evidence KW - German Hepatitis C-Registry Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281939 SN - 1999-4915 VL - 14 IS - 7 ER -