title: Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.
abstract: BACKGROUND
  The rate of development of liver fibrosis in hepatitis C virus (HCV) infection varies between individuals. This accounts for the variation in duration of progression to cirrhosis. The aims of this study were: (1) to determine whether fibrosis progresses linearly through the grading scales and (2) to identify factors which influence the rate of fibrosis.
  
  
  METHODS
  HCV infected patients who had undergone at least one liver biopsy were identified. Biopsies were scored using the modified HAI (Ishak) and METAVIR systems, which were compared. Patients were treatment naïve at first biopsy. Demographic features were examined for their relationship to fibrosis rate (defined as fibrosis stage/infection duration) using univariate and multivariate analysis. A subgroup of patients with two biopsies was examined to test the assumption that fibrosis progresses in a linear fashion.
  
  
  RESULTS
  A total of 917 patients were included. Male sex (p<0.00001), older age at infection (p</=0.00001), and viral genotype non-1 (p=0.005) were all associated with a rapid rate of fibrosis. On multiple linear regression they accounted for 29.5% of the variability in fibrosis rate (r(2)=0.295). METAVIR and Ishak scores were highly correlated (r=0.935, p<0.0001). In 137 patients who had two biopsies, the predicted probability for an increase of 1 on the fibrosis score was too low to assess linearity.
  
  
  CONCLUSIONS
  Demographic features account for a minority of fibrosis rate variability. The Ishak and METAVIR scoring systems are equivalent. Linearity of fibrosis progression cannot be assessed in biopsies only a few years apart.
authors.affiliation: Hepatology Section, Faculty of Medicine, Imperial College, London W2 1NY, UK. mark.wright@ic.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: R
authors.initials: R
authors.lastname: Goldin
authors.forename: A
authors.initials: A
authors.lastname: Fabre
authors.forename: J
authors.initials: J
authors.lastname: Lloyd
authors.forename: H
authors.initials: H
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Trepo
authors.forename: P
authors.initials: P
authors.lastname: Pradat
authors.forename: M
authors.initials: M
authors.lastname: Thursz
mesh_terms: D000328:Adult; D000367:Age Factors; D001706:Biopsy; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D016014:Linear Models; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology*; D008297:Male; D015203:Reproducibility of Results; D012307:Risk Factors; D012737:Sex Factors