Review article: HEPATITIS C VIRUS INFECTION: ESTABLISHMENT OF CHRONICITY AND LIVER DISEASE PROGRESSION

Hepatitis C virus (HCV) often causes persistent infection, and is an important factor in the etiology of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). There are no preventive or therapeutic vaccines available against HCV. Treatment strategies of HCV infection are likely to improve with recently discovered direct antiviral agents (DAAs). However, a propor-tion of patients still progress to liver failure and/or HCC despite having been cured of the in-fection. Thus, there is a need for early diagnosis and therapeutic modalities for HCV related end stage liver disease prevention. HCV genome does not integrate into its host genome, and has a predominantly cytoplasmic life cycle. Therefore, HCV mediated liver disease progres-sion appears to involve indirect mechanisms from persistent infection of hepatocytes. Study-ing the underlying mechanisms of HCV mediated evasion of immune responses and liver dis-ease progression is challenging due to the lack of a naturally susceptible small animal model. We and other investigators have used a number of experimental systems to investigate the mechanisms for establishment of chronic HCV infection and liver disease progression. HCV infection modulates immune systems. Further, HCV infection of primary human hepatocyte