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

Abstract

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.