@article{EstesAnsteeAriasLosteetal.2018,
  author    = {Estes, Chris and Anstee, Quentin M. and Arias-Loste, Maria Teresa and Bantel, Heike and Bellentani, Stefano and Caballeria, Joan and Colombo, Massimo and Craxi, Antonio and Crespo, Javier and Day, Christopher P. and Eguchi, Yuichiro and Geier, Andreas and Kondili, Loreta A. and Kroy, Daniela C. and Lazarus, Jeffrey V. and Loomba, Rohit and Manns, Michael P. and Marchesini, Giulio and Nakajima, Atsushi and Negro, Francesco and Petta, Salvatore and Ratziu, Vlad and Romero-Gomez, Manuel and Sanyal, Arun and Schattenberg, J{\"o}rn M. and Tacke, Frank and Tanaka, Junko and Trautwein, Christian and Wei, Lai and Zeuzem, Stefan and Ravazi, Homie},
  title     = {Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030},
  series = {Journal of Hepatology},
  volume    = {69},
  journal   = {Journal of Hepatology},
  doi       = {10.1016/j.jhep.2018.05.036},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227286},
  pages     = {896-904},
  year      = {2018},
  abstract  = {Background \& Aims Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. Methods A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. Results If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30\%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56\%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. Conclusions NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. Lay summary Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.},
  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{SchlevogtBoekerMaussetal.2021,
  author    = {Schlevogt, Bernhard and Boeker, Klaus H. W. and Mauss, Stefan and Klinker, Hartwig and Heyne, Renate and Link, Ralph and Simon, Karl-Georg and Sarrazin, Christoph and Serfert, Yvonne and Manns, Michael P. and Wedemeyer, Heiner},
  title     = {Weight gain after interferon-free treatment of chronic hepatitis C — results from the German Hepatitis C-Registry (DHC-R)},
  series = {Biomedicines},
  volume    = {9},
  journal   = {Biomedicines},
  number    = {10},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9101495},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248476},
  year      = {2021},
  abstract  = {Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (-0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48\%, 31\%, and 22\% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.},
  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}
}