title: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Digestive Disease Information & Research, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan. takumi@med.kurume-u.ac.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Eitaro
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Morita
authors.forename: Miki
authors.initials: M
authors.lastname: Shirachi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tateishi
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nagata
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000209:etiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects*; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000209:etiology; D008297:Male; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds