title: Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.
  
  
  OBJECTIVE
  To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.
  
  
  METHODS
  An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011.
  
  
  METHODS
  All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation.
  
  
  RESULTS
  The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P < .001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P < .001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P < .001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P < .001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P < .001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P < .001).
  
  
  CONCLUSIONS
  Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Adriaan J
authors.initials: AJ
authors.lastname: van der Meer
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Veldt
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Andres
authors.initials: A
authors.lastname: Duarte-Rojo
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kuske
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: W Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002170:Canada / Q000453:epidemiology; D002423:Cause of Death; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000401:mortality* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications* / Q000821:virology; D017093:Liver Failure / Q000150:complications / Q000821:virology; D008297:Male; D008875:Middle Aged; D014766:Viremia
chemical_list: D000998:Antiviral Agents; D007372:Interferons