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


CONCLUSIONS
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.
Donadon
Valter
V
Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Pordenone, Italy. valter.donadon@aopn.fvg.it
Balbi
Massimiliano
M
Ghersetti
Michela
M
Grazioli
Silvia
S
Perciaccante
Antonio
A
Della Valentina
Giovanni
G
Gardenal
Rita
R
Dal Mas
Maria
M
Casarin
Pietro
P
Zanette
Giorgio
G
Miranda
Cesare
C
D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008107:Liver Diseases / Q000150:complications* / Q000209:etiology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds