Mechanisms of HCV-induced liver cancer: What did we learn from in vitro and animal studies?

• Persistent HCV infection is the most common cause of HCC in many developed countries.
• Virus-induced inflammation and oxidative DNA damage are mechanisms of carcinogenesis.
• HCV infection disrupts several important tumor suppressor pathways.
• Progress in research on HCV-associated HCC depends on appropriate experimental models.
• New transgenic mouse models show promise in understanding of HCV-induced HCC.

Hepatitis C virus (HCV) is a cause of liver diseases that range from steatohepatitis, to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The challenge of understanding the pathogenesis of HCV-associated liver cancer is difficult as most standard animal models used in biomedical research are not permissive to HCV infection. Herein, we provide an overview of a number of creative in vivo, mostly in the mouse, and in vitro models that have been developed to advance our understanding of the molecular and cellular effects of HCV on the liver, specifically with their relevance to HCC.