title: Safety and Effectiveness of Direct-Acting Antiviral Agents for Treatment of Patients With Chronic Hepatitis C Virus Infection and Cirrhosis.
abstract: Direct-acting antivirals (DAAs) have revolutionized treatment for patients with chronic hepatitis C virus (HCV) infection, leading to a high rates of sustained virologic response. This study assessed the real-world safety and effectiveness of DAA-based antiviral therapy for the treatment of cirrhotic patients with chronic HCV infection.
  
  
  
  This international, multicenter cohort study included all consecutive patients with chronic HCV infection and cirrhosis who underwent antiviral therapy with second-generation DAAs. Data on all patients were analyzed to assess treatment response. Predictors of hepatic decompensation during antiviral therapy were assessed using Cox proportional hazards regression analyses.
  
  
  
  Until June 2015, 433 cirrhotic patients with chronic HCV infection started DAA-based treatment. Their mean age was 57.8 (±8.7) years, 277 (64.0%) patients were male, and 114 (26.3%) had a Child-Pugh (CP) score of B/C cirrhosis. The sustained virologic response rate at 12 weeks was similar among patients with a CP score of A (261 of 304 [85.9%]) and a CP score of B/C (83 of 101 [82.2%]; P = .37). A baseline albumin level less than 35 g/L (hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.23-7.84; P = .005), baseline MELD score of 14 or higher (HR, 1.63; 95% CI, 1.03-2.61; P = .037), and HCV genotype 3 (HR, 2.05; 95% CI, 1.09-3.88; P = .033) were associated independently with hepatic decompensation during antiviral treatment among patients with a CP score of B/C.
  
  
  
  This large cohort study showed that therapy is safe and effective in patients with compensated (CP score of A) cirrhosis. For patients with decompensated (CP score of B/C) cirrhosis, albumin level less than 35 g/L, MELD score of 14 or greater, and HCV genotype 3 are important risk factors for hepatic decompensation during DAA-based treatment. Therefore, these patients require close monitoring during antiviral therapy or treatment should be deferred until after transplantation.
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: r.maan@erasmusmc.nl.
authors.forename: Raoel
authors.initials: R
authors.lastname: Maan
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Tilborg
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alnoor
authors.initials: A
authors.lastname: Ramji
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: van der Meer
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Florence
authors.initials: F
authors.lastname: Wong
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Fung
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Morris
authors.initials: M
authors.lastname: Sherman
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.affiliation: Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D048550:Hepatic Insufficiency / Q000453:epidemiology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007391:International Cooperation; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents
keywords: Chronic Hepatitis C; Decompensation; Direct-Acting Antivirals; Safety