Obesity as a cause of hepatocellular carcinoma.

During recent years the incidence of obesity has increased significantly, and in some instances rapidly, in many resource-rich countries. Paralleling this increase has been an increase in the incidence of hepatocellular carcinoma. It has been estimated that as many as 90% of obese adults will develop the metabolic syndrome. The worldwide incidence of this syndrome in adults at this time ranges from 9 to 34%. Furthermore, obesity in childhood increases the risk of obesity in adulthood, and hence the development of the metabolic syndrome and hepatocellular carcinoma. Ten to 20% of patients with non-alcoholic fatty liver disease progress to non-alcoholic steatohepatitis, and 8.3% of the latter develop cirrhosis. Up to 50% of these patients with cirrhosis, and a significant proportion of those without cirrhosis, progress to hepatocellular carcinoma. Much remains to be learnt about the mechanisms by which obesity and the metabolic syndrome cause hepatocellular carcinoma, although insulin resistance, increased tissue necrosis factor activity, alterations in serum lipids, non-alcoholic fatty liver disease and non-alcoholic steatosis play important roles. There is also increasing evidence that gut microbiota play a role in the development of the metabolic syndrome and hence of hepatocellular carcinoma.