Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease.

Aim: To explore the association between hepatocellular carcinoma (HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk.

Methods: We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects. We evaluated the odds ratio (OR) for HCC by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.

Results: The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12 (CI 2.2-4.4, P < 0.001) and 2.2 (CI 1.2-4.4, P = 0.01). In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC. Moreover, we report an OR for HCC of 2.99 (CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.

Conclusion: Our study confirms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.