Insulin resistance and hepatocarcinogenesis

Hepatocellular carcinoma (HCC) accounts for 85–90% of liver cancers and is one of the most frequent carcinomas in the world. HCCs classically develop against the background of chronic liver diseases. Common causes of such liver diseases are viral hepatitis, alcoholic hepatitis, or immune-related diseases; however, 15–50% of patients with HCCs have none of these classic antecedents, especially in developed countries. In this context, obesity and diabetes mellitus have been found to exhibit an increased risk of HCC. Both conditions are associated with insulin resistance. The tumorigenic effects of insulin resistance and complementary hyperinsulinemia could be mediated directly by insulin signaling, or indirectly related to changes in endogeneous hormone metabolism, particularly insulin-like growth factor I. Conversely, insulin resistance may be a consequence of obesity and hepatic inflammation, both of which can themselves promote tumorigenesis, mainly through cytokine production and/or generation of oxidative stress. Because the prevalence of obesity is now increasing throughout the world, insulin resistance is sure to be emphasized as a major factor in hepatocarcinogenesis in the foreseeable future.