Insulin Resistance—a Link Between Inflammation and Hepatocarcinogenesis?

The incidence of hepatocellular carcinoma (HCC) is increasing world wide. The risk factors for the development of HCC include liver cirrhosis, chronic alcohol intake, and chronic viral hepatitis. These conditions are associated with inflammation, liver cell injury, and oxidative stress. The signaling pathways that contribute to liver cell injury have been shown to also promote insulin resistance in hepatocytes. On the other hand, obesity and diabetes have been suggested as risk factors for the development of chronic liver disease and HCC. The molecular mediators (e.g. stress kinases) and signaling pathways that contribute to cellular injury, proliferation and insulin resistance are also activated in chronic liver disease. At this time it is still unknown whether (1) IR will help to identify patients that are of increased risk for progressive liver disease or (2) if improving IR will be beneficial to patients with chronic liver disease. Future research will have to expand our knowledge on mediators of inflammation and liver cell injury within clinical trials to establish whether IR should be included in every hepatologists work up as a cofactor for chronic liver disease.