title: Early virological response may predict treatment response in sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center "real-life" cohort.
abstract: BACKGROUND
  The combination of sofosbuvir (SOF), ribavirin (RBV) and peg-interferon-alfa-2a (peg-IFN-alfa-2a) as well as the combination of SOF and RBV for the treatment of patients infected with hepatitis c virus (HCV) has improved rates of sustained virological response (SVR) considerably in recent trials. However, there is only limited data concerning the efficacy and safety in a "real-life" cohort.
  
  
  METHODS
  We analyzed a cohort of 119 patients with chronic HCV infection treated at four investigational sites in Germany. All patients received either a combination treatment of SOF, RBV and peg-IFN-alfa-2a or SOF and RBV.
  
  
  RESULTS
  The rates of SVR at 12 weeks after end of treatment (SVR 12) were as follows: Among 76 patients with genotype 1 infection the SVR 12 rate was 74% (n = 56), among 14 patients with genotype 2 infection the SVR 12 rate was 79% (n = 11), among 24 patients with genotype 3 infection the SVR 12 rate was 92% (n = 22) and among 5 patients with genotype 4 infection the SVR 12 rate was 80% (n = 4). Of all 26 patients with a relapse in our cohort, 69% (n = 18) of these patients presented with liver cirrhosis and 58% (n = 15) were treatment experienced. Notably, the level of HCV-RNA after 4 weeks of treatment was a significant predictor of treatment response in genotype 1 patients. Patients with HCV-RNA levels ≥ 12 IU ml-1 after 4 weeks of treatment achieved SVR 12 only in 30% (n = 17/56, p < 0.0001) of cases and treatment response was even lower with SVR 12 of 25% (n = 5/20, p = 0.0016) in the subgroup of patients with cirrhosis.
  
  
  CONCLUSIONS
  We observed a high rate of SVR 12 with SOF-based treatment regimes, however probably due to the high number of patients with liver cirrhosis and prior treatment experience, treatment response rates were lower than in previously published trials. In genotype 1 patients the analysis of early virological response may predict treatment response in SOF-based combination therapies.
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. niels.steinebrunner@med.uni-heidelberg.de.
authors.forename: Niels
authors.initials: N
authors.lastname: Steinebrunner
authors.affiliation: Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany. martin.sprinzl@unimedizin-mainz.de.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Sprinzl
authors.affiliation: Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany. tim.zimmermann@unimedizin-mainz.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.affiliation: Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany. marcus-alexander.woerns@unimedizin-mainz.de.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Wörns
authors.affiliation: Department of Internal Medicine II, University Hospital Mannheim, Mannheim, Germany. thomas.zimmerer@umm.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zimmerer
authors.affiliation: Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany. peter.galle@unimedizin-mainz.de.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. wolfgang.stremmel@med.uni-heidelberg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. christoph.eisenbach@med.uni-heidelberg.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisenbach
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital of Magdeburg, Magdeburg, Germany. kerstin.stein@med.ovgu.de.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Stein
authors.affiliation: Department of Internal Medicine II, University Hospital Mannheim, Mannheim, Germany. christoph.antoni@umm.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Antoni
authors.affiliation: Department of Internal Medicine I and Cirrhosis Center Mainz (CCM), University Medical Center Mainz, Mainz, Germany. joern.schattenberg@unimedizin-mainz.de.
authors.forename: Jörn M
authors.initials: JM
authors.lastname: Schattenberg
authors.affiliation: Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany. anita.pathil-warth@med.uni-heidelberg.de.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D019233:Retreatment; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir