Pathogenesis of hepatitis C virus

Hepatitis C virus (HCV) infects approximately 170 million people worldwide including 2 million in Japan and induces serious chronic hepatitis that results in the development of steatosis, cirrhosis and ultimately hepatocellular carcinoma. The current combination therapy using pegylated interferon alpha and a nucleotide analogue ribavirin achieved a sustained virological response in about half population of individuals infected with HCV genotypes la and lb. More than two-thirds of the HCV-positive population has been chronically infected with genotype 1 in Western countries and Japan. Therefore, more effective therapeutics and preventative measures are needed for the treatment of hepatitis C patients who are not responsive to the current chemotherapy. HCV core protein is well known to be the viral capsid protein as well as the pathogenic factor that induces steatosis and hepatocellular carcinoma in the transgenic mice. In this review, we summarize the current status of our knowledge regarding the molecular mechanism by which HCV core protein induces liver steatosis and hepatocellular carcinoma and discuss on a future perspective for the development of novel therapeutics for chronic hepatitis C.