Association of exogenous insulin or sulphonylurea treatment with an increased incidence of hepatoma in patients with hepatitis C virus infection

• Published in: Liver international Vol. 30; no. 3; pp. 479 - 486
• Main Authors: Kawaguchi, Takumi, Taniguchi, Eitaro, Morita, Yasuyo, Shirachi, Miki, Tateishi, Ikuo, Nagata, Eisuke, Sata, Michio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2010
• Subjects: Aging; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - etiology; Case-Control Studies; Cirrhosis; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Hepatitis C; Hepatitis C - complications; Hepatitis C virus; Hepatocellular carcinoma; Hepatoma; Hormones; Humans; Hypoglycemic Agents - adverse effects; Infection; Insulin; Insulin - adverse effects; Liver Cirrhosis - complications; Liver Cirrhosis - diagnosis; Liver Neoplasms - chemically induced; Liver Neoplasms - etiology; Male; Risk Factors; Sulfonylurea Compounds - adverse effects; sulphonylurea
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2009.02191.x

Background: Diabetes mellitus is frequently seen in hepatitis C patients and is often treated with antidiabetic agents that increase serum insulin levels. Because insulin is a growth‐promoting hormone, antidiabetic agents could pose a risk for hepatocellular carcinoma (HCC). Aim: The aim of this study was to investigate an association between antidiabetic therapies and the incidence of HCC in hepatitis C patients with diabetes mellitus. Methods: A nested case–control study was conducted. Participants were recruited from a cohort study, in which patients with hepatitis C were consecutively registered. Participants were assigned to an HCC group (n=138) or a non‐HCC group (n=103). To identify independent factors, variables including use of antidiabetic agents were analysed by logistic regression analysis. Results: Besides ageing, being male, cirrhosis and hypoalbuminaemia, use of exogenous insulin and a second‐generation sulphonylurea were significant independent factors associated with an incidence of HCC [odds ratio (OR) 2.969, 95% confidence interval (CI) 1.293–6.819, P<0.0103 and OR 6.831, 95% CI 1.954–23.881, P<0.0026 respectively). In stratified analyses, the impact of these antidiabetic agents was more evident in patients who were non‐cirrhotic than in those who were cirrhotic. Conclusions: Exogenous insulin and a second‐generation sulphonylurea were independent variables associated with an incidence of HCC in hepatitis C patients with diabetes mellitus. This association was evident in patients who were non‐cirrhotic. To verify a causal relationship between these antidiabetic agents and the development of HCC, a prospective cohort study is required.