@article{CornbergStoehrNaumannetal.2022,
  author    = {Cornberg, Markus and Stoehr, Albrecht and Naumann, Uwe and Teuber, Gerlinde and Klinker, Hartwig and Lutz, Thomas and M{\"o}ller, Hj{\"o}rdis and Hidde, Dennis and Lohmann, Kristina and Simon, Karl-Georg},
  title     = {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)},
  series = {Viruses},
  volume    = {14},
  journal   = {Viruses},
  number    = {7},
  issn      = {1999-4915},
  doi       = {10.3390/v14071541},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281939},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{WildeLiebLeichtetal.2021,
  author    = {Wilde, Anne-Christin Beatrice and Lieb, Charlotte and Leicht, Elise and Greverath, Lena Maria and Steinhagen, Lara Marleen and Wald de Chamorro, Nina and Petersen, J{\"o}rg and Hofmann, Wolf Peter and Hinrichsen, Holger and Heyne, Renate and Berg, Thomas and Naumann, Uwe and Schwenzer, Jeannette and Vermehren, Johannes and Geier, Andreas and Tacke, Frank and M{\"u}ller, Tobias},
  title     = {Real-world clinical management of patients with primary biliary cholangitis — a retrospective multicenter study from Germany},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10051061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234003},
  year      = {2021},
  abstract  = {Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3\% of patients, respectively. In 83.8\% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2\%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60\%, p = 0.005), Barcelona (13 vs. 34\%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75\%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74\%, p = 0.004; Barcelona: 50 vs. 84\%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86\%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.},
  language  = {en}
}
@article{HeidrichCordesKlinkeretal.2015,
  author    = {Heidrich, Benjamin and Cordes, Hans-J{\"o}rg and Klinker, Hartwig and M{\"o}ller, Bernd and Naumann, Uwe and R{\"o}ssle, Martin and Kraus, Michael R. and B{\"o}ker, Klaus H. and Roggel, Christoph and Schuchmann, Marcus and Stoehr, Albrecht and Trein, Andreas and Hardtke, Svenja and Gonnermann, Andrea and Koch, Armin and Wedemeyer, Heiner and Manns, Michael P. and Cornberg, Markus},
  title     = {Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0128069},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151811},
  pages     = {e0128069},
  year      = {2015},
  abstract  = {Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80\%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 \(\mu\)g/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68\% [55\%; 81\%] in Group A and 57\% [43\%; 71\%] in Group B achieved SVR (p=0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70\%) was not met. In conclusion, approximately 23\% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.},
  language  = {en}
}
@article{HeidrichWiegandBuggischetal.2014,
  author    = {Heidrich, Benjamin and Wiegand, Steffen B. and Buggisch, Peter and Hinrichsen, Holger and Link, Ralph and M{\"o}ller, Bernd and B{\"o}ker, Klaus H. W. and Teuber, Gerlinde and Klinker, Hartwig and Zehnter, Elmar and Naumann, Uwe and Busch, Heiner W. and Maasoumy, Benjamin and Baum, Undine and Hardtke, Svenja and Manns, Michael P. and Wedemeyer, Heiner and Petersen, J{\"o}rg and Cornberg, Markus},
  title     = {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},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0108751},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115149},
  pages     = {e108751},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}