The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans.

OBJECTIVE: Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC.

METHODS: All hospitalized patients with primary liver cancer (PLC) during 1997-1999 were identified in the computerized database of the Department of Veterans Affairs, the Patient Treatment File. Controls without cancer were randomly assigned from the Patient Treatment File during the same time period. The inpatient and outpatient files were searched for several conditions including DM, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic cirrhosis, autoimmune hepatitis, hemochromatosis, and nonspecific cirrhosis. Adjusted odds ratios (OR) were calculated in a multivariable logistic regression model.

RESULTS: We identified 823 patients with PLC and 3459 controls. The case group was older (62 yr [+/-10] vs 60 [+/-11], p < 0.0001), had more men (99% vs 97%, 0.0004), and a greater frequency of nonwhites (66% vs 71%, 0.0009) compared with controls. However, HCV- and HBV-infected patients were younger among cases than controls. Risk factors that were significantly more frequent among PLC cases included HCV (34% vs 5%, p < 0.0001), HBV (11% vs 2%, p < 0.0001), alcoholic cirrhosis (47% vs 6%, p < 0.0001), hemochromatosis (2% vs 0.3%, p < 0.0001), autoimmune hepatitis (5% vs 0.5%, p < 0.0001), and diabetes (33% vs 30%, p = 0.059). In the multivariable logistic regression, diabetes was associated with a significant increase in the adjusted OR of PLC (1.57, 1.08-2.28, p = 0.02) in the presence of HCV, HBV, or alcoholic cirrhosis. Without markers of chronic liver disease, the adjusted OR for diabetes and PLC was not significantly increased (1.08, 0.86-1.18, p = 0.4). There was an increase in the HCV adjusted OR (17.27, 95% Cl = 11.98-24.89) and HBV (9.22, 95% CI = 4.52-18.80) after adjusting for the younger age of HCV- and HBV-infected cases. The combined presence of HCV and alcoholic cirrhosis further increases the risk with an adjusted OR of 79.21 (60.29-103.41). The population attributable fraction for HCV among hospitalized veterans was 44.8%, whereas that of alcoholic cirrhosis was 51%.

CONCLUSION: DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis. Hepatitis C infection and alcoholic cirrhosis account for most of PLC among veterans.