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

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Association of exogenous insulin or sulphonylurea treatment with an increased

incidence of hepatoma in patients with hepatitis C virus infection

Authors: Kawaguchi, Takumi; Taniguchi, Eitaro1; Morita, Yasuyo; Shirachi, Miki;

Tateishi, Ikuo2; Nagata, Eisuke2; Sata, Michio

Source: Liver International, Volume 30, Number 3, March 2010 , pp. 479-486(8)

Publisher: Blackwell Publishing

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.

Document Type: Research article

DOI: 10.1111/j.1478-3231.2009.02191.x

Affiliations: 1: Department of Medicine, Kurume University School of Medicine,

Kurume University School of Medicine, Kurume, Japan 2: Nagata Hospital,

Shimomiyanaga-machi, Yanagawa, Japan