title: Hepatitis C virus dynamics during natural infection are associated with long-term histological outcome of chronic hepatitis C disease.
abstract: BACKGROUND
  The long-term dynamics of hepatitis C virus (HCV) infection and their association with hepatitis C disease are unknown.
  
  
  METHODS
  Fifty-two treatment-naive subjects with chronic HCV genotype 1 infection were selected from the Alaska Natives and American Indians cohort. Viral RNA levels were measured in 223 specimens (mean, 4.3 specimens/subject) over 457 patient-years. Viral quasispecies diversity was analyzed in 187 specimens (mean, 3.6 specimens/subject) over 365 patient-years.
  
  
  RESULTS
  Thirty-three subjects had minimal hepatic fibrosis, and 19 developed bridging fibrosis or cirrhosis. There was no significant difference in host variables, including alcohol consumption, between disease groups. Subjects with mild disease had higher serum RNA levels after 2 decades of infection (P=.013), greater fluctuations in RNA levels over time (P=.04), higher intraspecimen quasispecies diversity (P=.001), and higher rates of quasispecies diversification (P=.004) than did subjects with severe disease. On multivariate analysis, the odds of having severe disease were 15.3 (95% confidence interval, 2.3-99.6) times higher among persons with low quasispecies diversification rates compared with the odds among persons with high diversification rates.
  
  
  CONCLUSIONS
  Histological progression of hepatitis C is tightly associated with homogenization of HCV quasispecies, perhaps reflecting immune failure and/or selective outgrowth of aggressive viral variants.
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Sullivan
authors.forename: Dana
authors.initials: D
authors.lastname: Bruden
authors.forename: Heike
authors.initials: H
authors.lastname: Deubner
authors.forename: Susan
authors.initials: S
authors.lastname: McArdle
authors.forename: Minjun
authors.initials: M
authors.lastname: Chung
authors.forename: Carol
authors.initials: C
authors.lastname: Christensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Hennessy
authors.forename: Chriss
authors.initials: C
authors.lastname: Homan
authors.forename: James
authors.initials: J
authors.lastname: Williams
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.forename: David R
authors.initials: DR
authors.lastname: Gretch
mesh_terms: D000328:Adult; D018450:Disease Progression; D019143:Evolution, Molecular; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000473:pathology*; D020180:Heteroduplex Analysis; D006801:Humans; D007121:Immunocompetence; D007198:Indians, North American; D004930:Inuit; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D019562:Viral Load