Abstract
Background & AimsLiver 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.MethodsOur 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.ResultsSerum 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.ConclusionsWe 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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver injury in many countries [1,2]
Serum soluble type of CD14 (sCD14) levels were significantly associated with diagnosis of nonalcoholic steatohepatitis (NASH) and the area under the receiver operator characteristic curve (AUROC) to distinguish between not NASH and NASH was 0.802
Serum sCD14 levels were significantly associated with the disease activity based on nonalcoholic fatty liver disease (NAFLD) activity score and hepatic CD14 mRNA expression, which is correlated with membrane CD14 expression, in patients with NAFLD
Summary
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver injury in many countries [1,2]. Predicting the progression of simple steatosis to NASH and developing methods to facilitate the precise diagnosis of NASH are important targets for clinical research. Previous reports have shown that chronic liver inflammation is an important contributing factor to the pathogenesis of NASH and the key predictor of histological progression [9,10,11]. Invasive liver biopsy is still the only method to reliably detect liver inflammation and reach a definite diagnosis of NASH. This procedure is invasive and is associated with a relatively high risk of complications [14], emphasizing the clinical importance of PLOS ONE | www.plosone.org sCD14 and Liver Inflammation in NASH identifying biomarkers for liver inflammation in patients with NAFLD. The aim of this study was to investigate the relationship between soluble type of CD14 (sCD14) and histological features in patients with NAFLD
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