title: Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies.
abstract: OBJECTIVE
  Steatosis, a frequent histological finding in patients with chronic hepatitis C (CHC), has been suggested to influence liver fibrosis progression. The aim of the present study was to evaluate in patients with CHC and paired liver biopsies the relationship between the evolution of steatosis and that of fibrosis between the two biopsies.
  
  
  METHODS
  Ninety six patients were selected according to the following criteria: absence of treatment; absence of cirrhosis at initial biopsy; and serum hepatitis B surface antigen and human immunodeficiency virus antibody negativity. Degrees of necroinflammatory activity, fibrosis, and steatosis grades were assessed in the two biopsies. In addition to histological lesions, parameters studied included the source of infection, duration of infection, body mass index, alcohol intake, alanine aminotransferase levels, hepatitis C virus genotype, and viral load.
  
  
  RESULTS
  The mean interval between the two biopsies was 48 (32) months. Steatosis was found in 54% of patients at first biopsy, and was severe in 9%. Worsening of steatosis was observed in 34% of patients, stability in 50%, and improvement in 16%. Worsening of steatosis was significantly associated with hepatic fibrosis progression in patients with (p=0.03) or without (p<0.03) steatosis at diagnosis. Overall, fibrosis progression was observed in 31% of patients and stability in 69%. In a univariate analysis, fibrosis progression was associated with male sex (p=0.05), worsening of histological activity (p=0.04), and worsening of steatosis (p=0.0003). In a multivariate analysis, the only factor independently associated with fibrosis progression was worsening of steatosis (worsening v improvement/stability: odds ratio 4.7 (95% confidence interval 1.3-10.8); p=0.0001).
  
  
  CONCLUSIONS
  Our results suggest that in untreated patients with CHC and serial liver biopsies, fibrosis progression is strongly associated with worsening of steatosis.
authors.affiliation: Department of Virology (EA 3489), Centre Hospitalier Universitaire Henri Mondor, Université Paris-XII, Créteil, France. laurent.castera@chu-bordeaux.fr
authors.forename: L
authors.initials: L
authors.lastname: Castéra
authors.forename: C
authors.initials: C
authors.lastname: Hézode
authors.forename: F
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.forename: A
authors.initials: A
authors.lastname: Bastie
authors.forename: E-S
authors.initials: ES
authors.lastname: Zafrani
authors.forename: J-M
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: D
authors.initials: D
authors.lastname: Dhumeaux
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D000704:Analysis of Variance; D001706:Biopsy / Q000379:methods; D002908:Chronic Disease; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D006526:Hepatitis C / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors