Alpert Medical School of Brown University, Ocean State Research Institute, Providence Veterans Administration Medical Center, 830 Chalkstone Avenue, Providence, RI 02908, USA.
Hepatocellular carcinoma is the fifth most common human cancer worldwide, with an overall 5-year survival in the range of 10%. In addition to the very substantial role of chronic viral hepatitis in causing hepatocellular carcinoma, nutritional status and specific nutritional factors appear to influence disease risk. This is apparent in the increased risk associated with non-alcoholic hepatic cirrhosis occurring in the context of obesity, the metabolic syndrome, and type 2 diabetes. Specific nutrients and ingested toxins, including ethanol, aflatoxin, microcystins, iron, and possibly components of red meat, also are associated with increased hepatocellular carcinoma risk. Other dietary components, including omega-3 fatty acids and branched chain amino acids, may have protective effects. Recent data further suggest that several metabolic regulatory drugs, including metformin, pioglitazone, and statins, may have the potential to decrease the risk of hepatocellular carcinoma. The available data on these nutritional and metabolic factors in causing hepatocellular carcinoma are reviewed with the goal of identifying the strength of current knowledge and directions for future investigation.