title: Whole-body insulin resistance is associated with elevated serum α-fetoprotein levels in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC.
  
  
  METHODS
  We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver biopsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels (≥ 10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeostasis model assessment for insulin resistance value of ≥ 2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention.
  
  
  RESULTS
  A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic inflammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of < 15 × 10(4) /μL, aspartate aminotransferase level of ≥ 50 IU/L, γ-glutamyl transpeptidase level of ≥ 35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for insulin resistance and whole-body insulin sensitivity index.
  
  
  CONCLUSIONS
  Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mizuta
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sakurai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Motomura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isoda
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuwashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oeda
authors.forename: Shinji
authors.initials: S
authors.lastname: Iwane
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Keizo
authors.initials: K
authors.lastname: Anzai
authors.forename: Iwata
authors.initials: I
authors.lastname: Ozaki
mesh_terms: D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D010865:Pilot Projects; D012189:Retrospective Studies; D040242:Risk Reduction Behavior; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: C097353:AFP protein, human; D015415:Biomarkers; D000509:alpha-Fetoproteins; D001219:Aspartate Aminotransferases