title: Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.
abstract: OBJECTIVE
  Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region.
  
  
  METHODS
  We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration.
  
  
  RESULTS
  Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis.
  
  
  CONCLUSIONS
  We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.
authors.affiliation: Division of Clinical Pathology, University Hospital, Geneva, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: R
authors.initials: R
authors.lastname: Quadri
authors.forename: K
authors.initials: K
authors.lastname: Abid
authors.forename: E
authors.initials: E
authors.lastname: Giostra
authors.forename: P J
authors.initials: PJ
authors.lastname: Malé
authors.forename: G
authors.initials: G
authors.lastname: Mentha
authors.forename: L
authors.initials: L
authors.lastname: Spahr
authors.forename: J P
authors.initials: JP
authors.lastname: Zarski
authors.forename: B
authors.initials: B
authors.lastname: Borisch
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
authors.forename: F
authors.initials: F
authors.lastname: Negro
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use; D005234:Fatty Liver / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D007121:Immunocompetence; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D019590:Nucleocapsid Proteins; D012367:RNA, Viral