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 confi rms 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.

Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma

AIM: To evaluate the relationship between glycemic control [assessed by glycated hemoglobin (HbA1c)], antidiabetic therapies and the risk of hepatocellular carcinoma (HCC).METHODS: We recruited 465 patients with HCC, 618 cases with liver cirrhosis and 490 controls with no liver disease. Among subjects with type 2 diabetes mellitus (DM2), the associations between the antidiabetic strategies and HbA1c level with HCC were determined through 2 series of multivariate logistic regression models using cirrhotic patients and controls as comparison groups. RESULTS: DM2 prevalence was 31.2% in patients with HCC, 23.2% in cirrhotic patients and 12.6% in controls (P < 0.0001). In 86% of study subjects, DM2 had been diagnosed for more than 1 year before the HCC diagnosis. HCC patients with DM2 had a 1.52.5fold increased risk of liver cancer. The HbA1c mean levels were signif icantly higher in DM2 patients with HCC than in cirrhoticand control DM2 patients. Antidiabetic treatment with metformin was more common among cirrhotic and control DM2 subjects than among cases with HCC. In both series of multivariate analyses, treatment with metformin signif icantly reduced the risk of HCC by more than 80% compared with sulphonylureas and insulin therapy. No signif icant differences were seen between sulphonylureas and insulin treatment. Elevated HbA1c levels were positively related to the risk for HCC in diabetic patients, with a 26%50% increase in risk for each 1% increase in HbA1c values.CONCLUSION: In patients with preexisting DM2, the risk of HCC is positively associated with poor chronic glycemic control and significantly decreased by metformin therapy.

Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy:Potential role of insulin

AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS: We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC (78.3% males, mean age 68.5 ± 8.9 years) compared with an age and sex matched control group of 490 subjects. RESULTS: Prevalence of DM2 was significantly higher in HCC patients (31.2% vs 12.7%; OR = 3.12, 95% CI: 2.22-4.43) and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents (171.5 vs 118.7 mo). Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049). CONCLUSION: DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.