Impact of the Hepatitis C Virus Variability on Liver Steatosis

Chronic infection by the hepatitis C virus (HCV) is a common cause of liver disease, which may progress to cirrhosis and eventually liver cancer. The therapeutic indication will depend mainly on the importance of liver damage (fibrosis), which can be assessed by physical techniques, blood tests and a liver biopsy. The overall objectives of the project are to understand how HCV variability may influence the severity of steatosis (accumulation of fat in the liver), studying 30 patients chronically infected with HCV (half of these patients infected by HCV genotype 3, versus the other half infected by HCV of another genotype). A small portion of the biopsy performed for the routine pathology examination will be placed in special fixation buffer for electron microscopy (EM). Counting and measuring the size of lipid droplets present in the liver by EM will be used to precisely quantify and characterize the liver steatosis. A blood sample of patients will also be collected to sequence the viral genome present in the patient and identify the amino acids involved in an increase in intracellular accumulation of lipid droplets. This work should clarify the impact of the viral variability in the severity of steatosis. Ultimately, the identification of viral sequences responsible for an increase of this phenomenon could be crucial for understanding the mechanisms involved in the steatosis.