title: Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects.
abstract: OBJECTIVE
  Fetuin-A (α2HS-glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)-β1 signalling inhibitor. Serum fetuin-A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin-A as a predictive fibrosis biomarker in NAFLD patients remains unclear. In this study, we investigated the relationship between circulating fetuin-A levels and fibrosis-related markers [platelet count, NAFLD fibrosis score and carotid intima media thickness (IMT)] in subjects with NAFLD.
  
  
  METHODS
  A total of 295 subjects (male, 164; female, 131) who received medical health check-ups were enrolled in this study. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin-A was measured by ELISA. IMT was assessed using a high-resolution ultrasound scanner. Using recombinant human fetuin-A, we investigated the effects of fetuin-A on hepatic stellate cells, which play a pivotal role in the process of hepatic fibrosis.
  
  
  RESULTS
  Serum fetuin-A concentration was significantly correlated with platelet count (R = 0.19, P < 0.01), NAFLD fibrosis score (R = -0.25, P < 0.01) and mean IMT (R = -0.22, P < 0.01). Multivariate analyses revealed that the fetuin-A concentration is a significant and independent determinant of platelet count, NAFLD fibrosis score and mean IMT. Recombinant fetuin-A suppressed TGF-β1 signalling and fibrosis-related gene expression and increased the expression of TGF-β1 pseudoreceptor bone morphogenic protein and activin membrane-bound inhibitor (BAMBI).
  
  
  CONCLUSIONS
  Serum fetuin-A level is associated with liver/vessel fibrosis-related markers in NAFLD patients. Circulating fetuin-A could be a useful serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients.
authors: Department of Molecular Biochemistry & Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
authors: Motoya
authors: M
authors: Sato
authors: Yoshihiro
authors: Y
authors: Kamada
authors: Yuri
authors: Y
authors: Takeda
authors: Sachiho
authors: S
authors: Kida
authors: Yuka
authors: Y
authors: Ohara
authors: Hironobu
authors: H
authors: Fujii
authors: Maaya
authors: M
authors: Akita
authors: Kayo
authors: K
authors: Mizutani
authors: Yuichi
authors: Y
authors: Yoshida
authors: Makoto
authors: M
authors: Yamada
authors: Hidetaka
authors: H
authors: Hougaku
authors: Tetsuo
authors: T
authors: Takehara
authors: Eiji
authors: E
authors: Miyoshi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D059168:Carotid Intima-Media Thickness; D002460:Cell Line; D005260:Female; D005355:Fibrosis; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000473:pathology; D010976:Platelet Count; D053773:Transforming Growth Factor beta1; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D060749:alpha-2-HS-Glycoprotein
keywords: BAMBI; IMT; NASH/NAFLD; TGF-β1