title: Safety and efficacy of protease inhibitor based combination therapy in a single-center "real-life" cohort of 110 patients with chronic hepatitis C genotype 1 infection.
abstract: BACKGROUND
  The combination of boceprevir or telaprevir with peginterferon-alfa and ribavirin for the treatment of patients infected with HCV genotype 1 has led to significantly increased rates of sustained virological response (SVR) in phase III trials. There is only limited data regarding the safety and efficacy in a "real-life" cohort.
  
  
  METHODS
  We analyzed a cohort of 110 unselected HCV patients who started triple therapy from September 2011 to February 2013 by chart review with focus on the individual course of treatment, complications and outcome. We excluded 8 patients from analysis because of HIV-coinfection (N = 6) or status post liver transplant (N = 2). Importantly, 41 patients displayed F3 or F4 fibrosis, 10 patients had a history of treatment with protease/polymerase inhibitors and 15 patients were prior partial- or null-responder.
  
  
  RESULTS
  SVR12 was achieved in 62 of the 102 patients (60.8%). A high rate of serious adverse events (N = 30) was observed in 22 patients including 2 fatalities in cirrhotic diabetes patients. Age >50 years, liver cirrhosis, bilirubin >1.1 mg/dl (P < 0.01, each), platelets <100,000/μl (P = 0.01), ASAT >100 U/l (P = 0.03) and albumin ≤35 g/l (P = 0.04) at baseline were associated with occurence of a SAE.
  
  
  CONCLUSIONS
  The frequency of SVR in a "real-life" treatment setting is slightly lower as compared to the results of the phase III trials for telaprevir or boceprevir. Importantly, we observed a high frequency of SAE in triple therapy, especially in patients with liver cirrhosis.
authors.forename: Malte H
authors.initials: MH
authors.lastname: Wehmeyer
authors.forename: Friederike
authors.initials: F
authors.lastname: Eißing
authors.forename: Sabine
authors.initials: S
authors.lastname: Jordan
authors.forename: Claudia
authors.initials: C
authors.lastname: Röder
authors.forename: Annette
authors.initials: A
authors.lastname: Hennigs
authors.forename: Olaf
authors.initials: O
authors.lastname: Degen
authors.forename: Anja
authors.initials: A
authors.lastname: Hüfner
authors.forename: Sandra
authors.initials: S
authors.lastname: Hertling
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmiedel
authors.forename: Martina
authors.initials: M
authors.lastname: Sterneck
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: I, Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Martinistr, 52, Hamburg 20246, Germany. j.schulze-zur-wiesch@uke.de.
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze zur Wiesch
authors.forename: Stefan
authors.initials: S
authors.lastname: Lüth
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline