Brief Articles
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World J Gastroenterol. May 28, 2009; 15(20): 2506-2511
Published online May 28, 2009. doi: 10.3748/wjg.15.2506
Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease
Valter Donadon, Massimiliano Balbi, Michela Ghersetti, Silvia Grazioli, Antonio Perciaccante, Giovanni Della Valentina, Rita Gardenal, Maria Dal Mas, Pietro Casarin, Giorgio Zanette, Cesare Miranda
Valter Donadon, Massimiliano Balbi, Michela Ghersetti, Silvia Grazioli, Antonio Perciaccante, Giovanni Della Valentina, Rita Gardenal, Maria Dal Mas, Pietro Casarin, Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Via Montereale 24, Pordenone 33170, Italy
Giorgio Zanette, Cesare Miranda, Diabetes Clinic, Pordenone Hospital, Via Montereale 24, Pordenone 33170, Italy
Author contributions: Donadon V conceived and designed the research; Ghersetti M, Grazioli S, Della Valentina G, Gardenal R, Casarin P, Zanette G, Miranda C performed the research, diagnosis and patient follow-up; Perciaccante A, Balbi M, Dal Mas M, analyzed the data; Donadon V, Balbi M, Perciaccante A wrote the paper; Donadon V revised the paper.
Correspondence to: Dr. Valter Donadon, Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Via Montereale 24, Pordenone 33170, Italy. valter.donadon@aopn.fvg.it
Telephone: +39-434-399330
Fax: +39-434-399559
Received: March 11, 2009
Revised: April 29, 2009
Accepted: May 6, 2009
Published online: May 28, 2009
Abstract

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.

Keywords: Hepatocellular carcinoma, Type 2 diabetes mellitus, Insulin, Sulphanylureas, Metformin