Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma.

Coinciding with the increased incidence of hepatocellular carcinoma (HCC), there has been a significant increase in the global incidence of obesity and diabetes mellitus (DM), the two major risk factors for nonalcoholic steatohepatitis (NASH). There are many causes of HCC, and nonalcoholic fatty liver disease/NASH is now emerging as a leading risk factor owing to the epidemic of obesity and type 2 DM. The mechanisms leading to HCC in obesity and type 2 DM likely involve interactions between several signaling pathways, including oxidative stress, inflammation, oncogenes, adiponectins, and insulin resistance associated with visceral adiposity and diabetes.