title: Limited effectiveness and safety profile of protease inhibitor-based triple therapy against chronic hepatitis C in a real-world cohort with a high proportion of advanced liver disease.
abstract: OBJECTIVE
  Triple therapy with pegylated-interferon-α, ribavirin, and a protease inhibitor (PI), boceprevir or telaprevir, is the standard of care for the treatment of chronic hepatitis C genotype 1 in several countries. Pivotal studies showed reasonable results for safety and efficacy. However, it remains uncertain to what extent this can be transferred to the real world.Here, we aimed to analyze the effectiveness and safety of pegylated-interferon-α/ribavirin/PI triple therapy in a real-world cohort of a tertiary referral center.
  
  
  METHODS
  Between June 2011 and November 2011, a total of 208 consecutive patients with chronic hepatitis C genotype 1 were evaluated for the initiation of a triple-therapy regimen and included in this study. Eighty-six patients (86% F3/F4) started a triple-therapy regimen and were followed until 12 weeks after the end of treatment.
  
  
  RESULTS
  Overall, 36 out of the 86 treated patients (42%) achieved a sustained virological response. However, only 17% of the initially screened 208 patients were cured with triple therapy at our center. A high rate of serious adverse events (28%) was documented during treatment. The risk/benefit ratio was poor for patients with signs of advanced liver cirrhosis (n=33, 38%), indicated by increased bilirubin, low albumin, and/or low platelet count at baseline.
  
  
  CONCLUSIONS
  The effectiveness and safety of PI-based triple therapy can be limited in real-world cohorts including large numbers of patients with advanced liver disease. Future therapies can only overcome these limitations if interferon-free regimens are established.
authors.affiliation: aDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany bDepartment of Infectious Diseases and Hepatology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Maasoumy
authors.forename: Kerstin
authors.initials: K
authors.lastname: Port
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.forename: Christoph
authors.initials: C
authors.lastname: Höner Zu Siederdissen
authors.forename: Antoaneta A
authors.initials: AA
authors.lastname: Markova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rogalska-Taranta
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011480:Protease Inhibitors; D012254:Ribavirin