Incidence rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have increased in the United States. Metabolic syndrome is recognized as a risk factor for HCC and may also modify risk for ICC. The magnitude of this effect, however, has not been investigated on a population level in the US. We therefore examined the association between metabolic syndrome and the development of both primary liver cancers in the general population. All persons diagnosed with HCC and ICC between 1993 and 2005 were identified in the SEER-Medicare database. For comparison, a 5% sample of individuals residing in the same geographic regions as the SEER registries of the cases was selected.

The prevalence of metabolic syndrome as defined by the US National Cholesterol Education Program Adult Treatment Panel III criteria, and other risk factors for HCC (HBV, HCV, alcoholic liver disease, liver cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, HBV, HCV, alcoholic liver disease, cirrhosis, inflammatory bowel disease) were compared among persons who developed cancer and the persons who did not. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals.

A total of 3649 HCC cases, 743 ICC cases and 195953 persons without cancer met the inclusion criteria. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than persons who did not (17.1%, p<<0.0001). In adjusted multiple logistic regression analyses, metabolic syndrome remained significantly associated with increased risk of HCC (OR=2.13; 95%CI=1.96-2.31, p<0.0001) and ICC (OR=1.56; 95% CI= 1.32-1.83, p<0.0001). Conclusions: Metabolic syndrome is a significant risk factor for development of HCC and ICC in the general U.S. population.