Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3

Background/Aims: Patients infected with the hepatitis C virus (HCV) often h ave liver steatosis, suggesting the possibility of a viral cytopathic effec t, The aim of this study was to correlate the occurrence and severity of li ver steatosis with HCV RNA type, level and sequence of the core-encoding re gion. Methods: We scored the liver steatosis in 101 HCV-infected individuals care fully 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 p atients, we assessed the effect of antiviral therapy on steatosis and the r elationship between nucleocapsid sequence heterogeneity and fat infiltratio n. Results: Steatosis was found in 41 (40.6%) patients, irrespective of sex, a ge or route of infection. HCV genotype 3 was associated with higher steatos is scores than other genotypes, A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected wit h genotype 3, but not in those infected with genotype 1. In selected patien ts, response to alpha-interferon was associated with the disappearance of s teatosis, Analysis of the nucleocapsid of 14 HCV isolates failed to identif y a sequence specifically associated with the development of steatosis. Conclusions: We provide virological and clinical evidence that the steatosi s of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3, At variance with published evide nce from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.