HCV-related hepatocellular carcinoma: From chronic inflammation to cancer.

Hepatitis C virus (HCV) infection, a worldwide health problem, can evolve into chronic disease, cirrhosis, and/or hepatocellular carcinoma (HCC). Although viral, genetic, and epigenetic factors play a significant role, the host immune response is critical in determining whether the outcome of HCV infection is progressive disease characterized by a lack of protective antibodies and inefficient cytotoxic responses. For viral clearance, combined innate and adaptive immune responses are required; resolution requires a vigorous, durable, polyclonal CD4+ and CD8+ T-cell response, with an increase in virus-specific CD8+ T cells or cytotoxic T lymphocytes. Failure of a formerly efficient immune response can lead to chronic inflammation; excessive tissue remodeling; and loss of tissue architecture from cell growth, apoptosis and/or necrosis, and induction of oxidative stress; these changes promote the development of fibrosis and/or cirrhosis and a microenvironment conducive to genomic instability mutations, and increased risk of cancer development. System governance is achieved by close interaction between the cellular (regulatory cells) and humoral (cytokines and monokines) immune networks. In this review, we highlight the magnitude of the HCC problem and the status of the biologic, genetic, and immunologic defenses against HCV. Conclusion: HCC pathogenesis represents a model of progression from chronic inflammation to cancer and thus should allow design of new treatment strategies for HCV infection, a devastating global disease. We are confident that such strategies are possible today by altering the microenvironment that conditions the immune response, thereby modifying disease outcome.