| Abstract: | The mechanism by which hepatitis C virus (HCV) causes chronic, progressive liver damage is unknown. Factors other than the virus itself have been implicated. The role of liver steatosis has been recently studied. Hepatic steatosis is a common histologic finding occurring in >50% of patients with chronic hepatitis C. Both host and viral factors have been demonstrated to play an important role in its development. In patients infected with genotype 1, steatosis appears due to co-existence of Non-alchoholic steatohepatitis (NASH) with HCV and associated with increased body mass index (BMI). Some recent observations suggest that steatosis may be of viral origin and related to genotype 3. This fact raises the possibility of a direct effect of specific viral sequences on the pathogenesis of lipid accumulation. Furthermore, hepatic steatosis attributed to genotype 3 correlates directly with serum and intrahepatic titers of HCV RNA. Resolution of steatosis after successful antiviral therapy as well as steatosis being a sign of recurrent HCV infection in patients with genotype 3 add convincing evidence that steatosis is viral-related. The pathogenic mechanism induced by genotype 3 is speculative. Correlation between steatosis, intrahepatic HCV RNA, and core protein expression suggest a direct effect. Further support is provided by the finding that HCV core protein induces steatosis in transgenic mice. Another possibility relates to interaction with hepatic triglyceride turnover. In conclusion, for patients infected with genotype 1 BMI plays a role in the pathogenesis of steatosis, while in those infected with genotype 3 steatosis may be due to a virus-specific cytopathic effect. Regardless of etiology, the contribution of both to liver fibrosis progression appears to be accepted. |
