title: Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C.
abstract: BACKGROUND
  Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients.
  
  
  METHODS
  A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3 ± 10.8 years; 95 females, mean age 56.6 ± 10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy.
  
  
  RESULTS
  Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development.
  
  
  CONCLUSIONS
  Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Nabeshima, Saga, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mizuta
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuwashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isoda
authors.forename: Noriko
authors.initials: N
authors.lastname: Oza
authors.forename: Shinji
authors.initials: S
authors.lastname: Iwane
authors.forename: Kenichi
authors.initials: K
authors.lastname: Izumi
authors.forename: Keizou
authors.initials: K
authors.lastname: Anzai
authors.forename: Iwata
authors.initials: I
authors.lastname: Ozaki
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology / Q000821:virology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000175:diagnosis; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors