HCV-related hepatocellular carcinoma: From chronic inflammation to cancer.
Hepatitis C virus (HCV) infection is a worldwide health problem because of its incidence and pathogenicity. It might evolve into chronic disease, cirrhosis, and/or hepatocellular carcinoma (HCC) and the outcome is mainly determined by the host immune response. 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 efficient immune response can lead to chronic inflammation, tissue remodeling through cell growth, apoptosis and/or necrosis and induction of oxidative stress. Development of fibrosis and/or cirrhosis plus a microenvironment conducive to genomic instability mutations will promote neoplastic transformation. System governance derives from cellular (regulatory cells) and humoral (cytokines and chemokines) immune networks. Therefore, HCC pathogenesis may be a model to study the disease progression from chronic inflammation to cancer allowing design of new strategies targeting the immune response, thereby modifying disease outcome.
Castello
Giuseppe
G
Oncology Research Centre, Mercogliano, AV, Italy. giuseppe.castello@cro-m.eu
Scala
Stefania
S
Palmieri
Giuseppe
G
Curley
Steven A
SA
Izzo
Francesco
F
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008297:Male