Soluble CD14 levels reflect liver inflammation in patients with nonalcoholic steatohepatitis

PLoS One. 2013 Jun 7;8(6):e65211. doi: 10.1371/journal.pone.0065211. Print 2013.

Abstract

Background aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Case-Control Studies
  • Cell Line
  • Fatty Liver / blood*
  • Fatty Liver / pathology
  • Female
  • Humans
  • Inflammation / blood*
  • Inflammation / pathology*
  • Lipopolysaccharide Receptors / blood*
  • Lipopolysaccharides / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Mice
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • ROC Curve
  • Regression Analysis
  • Solubility

Substances

  • Lipopolysaccharide Receptors
  • Lipopolysaccharides

Grants and funding

Work in the authors’ laboratory was supported by the program “Step A” from the Japan Science and Technology Agency (JST) and Kiban-B, Shingakujuturyouiki. In addition, the present work was supported in part by grants-in-aid from the Japanese Ministry of Health, Labour and Welfare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.