title: Soluble CD14 levels reflect liver inflammation in patients with nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Liver inflammation is a risk factor for the progression of nonalcoholic fatty liver disease (NAFLD). However, the diagnosis of liver inflammation is very difficult and invasive liver biopsy is still the only method to reliably detect liver inflammation. We previously reported that overexpression of CD14 in Kupffer cells may trigger the progression to nonalcoholic steatohepatitis (NASH) via liver inflammation following hyper-reactivity to low-dose lipopolysaccharide. Therefore, the aim of this study was to investigate the relationship between soluble type of CD14 (sCD14) and histological features in patients with NAFLD.
  
  
  METHODS
  Our cohort consisted of 113 patients with liver biopsy-confirmed NAFLD and 21 age-matched healthy controls. Serum sCD14 levels were measured by an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Serum sCD14 levels were significantly associated with diagnosis of NASH and the area under the receiver operator characteristic curve (AUROC) to distinguish between not NASH and NASH was 0.802. Moreover, serum sCD14 levels were significantly associated with the disease activity based on NAFLD activity score and hepatic CD14 mRNA expression, which is correlated with membrane CD14 (mCD14) expression, in patients with NAFLD. In multiple regression analysis, the serum sCD14 levels were independently associated with liver inflammation. The AUROC to distinguish between mild and severe liver inflammation in patients with NAFLD was 0.752.
  
  
  CONCLUSIONS
  We found that serum sCD14 levels increased significantly with increasing liver inflammation grade in patients with NAFLD, reflecting increased hepatic CD14 expression. Serum sCD14 is a promising tool to predict the worsening of liver inflammation, and may offer a potential biomarker for evaluation of therapeutic effects in NAFLD.
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kessoku
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012372:ROC Curve; D012044:Regression Analysis; D012995:Solubility
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides