Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis

Clin Exp Pharmacol Physiol. 2016 Jan;43(1):13-21. doi: 10.1111/1440-1681.12499.

Abstract

An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

Keywords: neutrophil elastase; nonalcoholic steatohepatitis; α1-antitrypsin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Disease Progression
  • Female
  • Fibrosis
  • Humans
  • Inflammation / blood
  • Insulin Resistance
  • Leukocyte Elastase / blood*
  • Liver / enzymology
  • Liver / pathology*
  • Male
  • Neutrophils / cytology
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / pathology
  • alpha 1-Antitrypsin / blood*

Substances

  • Blood Glucose
  • alpha 1-Antitrypsin
  • Leukocyte Elastase