title: Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.
abstract: OBJECTIVE
  While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression.
  
  
  METHODS
  We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models.
  
  
  RESULTS
  Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001).
  
  
  CONCLUSIONS
  This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.
authors: Department of Internal Medicine, Infectious Diseases Service, CHUV, Lausanne, Switzerland.
authors: Pierre-Yves
authors: PY
authors: Bochud
authors: Tao
authors: T
authors: Cai
authors: Kathrin
authors: K
authors: Overbeck
authors: Murielle
authors: M
authors: Bochud
authors: Jean-François
authors: JF
authors: Dufour
authors: Beat
authors: B
authors: Müllhaupt
authors: Jan
authors: J
authors: Borovicka
authors: Markus
authors: M
authors: Heim
authors: Darius
authors: D
authors: Moradpour
authors: Andreas
authors: A
authors: Cerny
authors: Raffaele
authors: R
authors: Malinverni
authors: Patrick
authors: P
authors: Francioli
authors: Francesco
authors: F
authors: Negro
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013557:Switzerland; D013997:Time Factors; D055815:Young Adult