Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database

Hepatology. 2011 Aug;54(2):463-71. doi: 10.1002/hep.24397. Epub 2011 Jun 30.


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 a postulated one for ICC. The magnitude of risk, however, has not been investigated on a population level in the United States. We therefore examined the association between metabolic syndrome and the development of these cancers. All persons diagnosed with HCC and ICC between 1993 and 2005 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. For comparison, a 5% sample of individuals residing in the same regions as the SEER registries of the cases was selected. The prevalence of metabolic syndrome as defined by the U.S. National Cholesterol Education Program Adult Treatment Panel III criteria, and other risk factors for HCC (hepatitis B virus, hepatitis C virus, alcoholic liver disease, liver cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, hepatitis B virus, hepatitis C virus, alcoholic liver disease, cirrhosis, inflammatory bowel disease) were compared among persons who developed cancer and those who did not. Logistic regression was used to calculate odds ratios and 95% confidence intervals. The inclusion criteria were met by 3649 HCC cases, 743 ICC cases, and 195,953 comparison persons. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than the comparison group (17.1%, P<0.0001). In adjusted multiple logistic regression analyses, metabolic syndrome remained significantly associated with increased risk of HCC (odds ratio=2.13; 95% confidence interval=1.96-2.31, P<0.0001) and ICC (odds ratio=1.56; 95% confidence interval=1.32-1.83, P<0.0001).

Conclusion: Metabolic syndrome is a significant risk factor for development of HCC and ICC in the general U.S. population.

MeSH terms

  • Aged
  • Bile Duct Neoplasms / epidemiology
  • Bile Duct Neoplasms / etiology*
  • Bile Ducts, Intrahepatic
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology*
  • Cholangiocarcinoma / epidemiology
  • Cholangiocarcinoma / etiology*
  • Databases, Factual
  • Female
  • Humans
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology*
  • Male
  • Medicare
  • Metabolic Syndrome / complications*
  • Regression Analysis
  • Risk Factors
  • United States / epidemiology