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Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study
  1. J A Davila1,
  2. R O Morgan1,
  3. Y Shaib2,
  4. K A McGlynn3,
  5. H B El-Serag2
  1. 1Section of Health Services Research, Houston Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
  2. 2Section of Health Services Research, and Section of Gastroenterology, Houston Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
  3. 3Division of Cancer Epidemiology and Genetics, NCI/DHHS, USA
  1. Correspondence to:
    Dr H B El-Serag
    Houston Veterans Affairs Medical Center, 2002 Holcombe Blvd. (152), Houston, TX 77030, USA;


Background: Diabetes has been associated with an increased risk of hepatocellular carcinoma (HCC) in studies of referred patients. This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC.

Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)-Medicare linked database to identify patients aged 65 years and older diagnosed with HCC and randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index date were examined. Inpatient and outpatient claims files were searched for diagnostic codes indicative of diabetes, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease, and haemochromatosis. HCC patients without these conditions were categorised as idiopathic. Unadjusted and adjusted odds ratios were calculated in logistic regression analyses.

Results: We identified 2061 HCC patients and 6183 non-cancer controls. Compared with non-cancer controls, patients with HCC were male (66% v 36%) and non-White (34% v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis), diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjusted odds ratio for diabetes declined but remained significant (adjusted odds ratio 2.87 (95% confidence interval 2.49–3.30)). A significant positive interaction between HCV and diabetes was detected (p<0.0001). Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis.

Conclusions: Diabetes is associated with a 2–3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk factors. Findings from this population based study suggest that diabetes is an independent risk factor for HCC.

  • SEER, Surveillance, Epidemiology, and End-Results Program
  • HCC, hepatocellular carcinoma
  • HBV, hepatitis B virus
  • HCV, hepatitis C virus
  • NAFLD, non-alcoholic fatty liver disease
  • NASH, non-alcoholic steatohepatitis
  • HMO, health maintenance organisation
  • OR, odds ratio
  • HIV, human immunodeficiency virus
  • diabetes
  • hepatocellular carcinoma
  • Surveillance Epidemiology and End-Results Program
  • epidemiology
  • hepatoma

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  • Conflict of interest: None declared.

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