Liver cancer is a global problem and hepatocellular carcinoma (HCC) accounts for about 85% of this cancer. In the USA, etiologies and risk factors for HCC include chronic hepatitis C virus (HCV) infection, diabetes, non-alcoholic steatohepatitis (NASH), obesity, excessive alcohol drinking, exposure to tobacco smoke, and genetic factors. Chronic HCV infection appears to be associated with about 30% of HCC. Chronic HCV infection induces multistep changes in liver, involving metabolic disorders, steatosis, cirrhosis and HCC. Liver carcinogenesis requires initiation of neoplastic clones, and progression to clinically diagnose malignancy. Tumor progression associates with profound exhaustion of tumor-antigen-specific CD8T cells, and accumulation of PD-1 CD8T cells and Tregs. In this chapter, we provide a brief description of HCV and environmental/genetic factors, immune regulation, and highlight mechanisms of HCV associated HCC. We also underscore HCV treatment and recent paradigm of HCC progression, highlighted the current treatment and potential future therapeutic opportunities.
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