title: Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis.
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.
authors.affiliation: Department of Endocrinology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.|Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Shufei
authors.initials: S
authors.lastname: Zang
authors.affiliation: Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ma
authors.affiliation: Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Bian
authors.affiliation: Department of Liver Diseases, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China.
authors.forename: Yunhao
authors.initials: Y
authors.lastname: Xun
authors.affiliation: Department of Endocrinology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Health Management, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Falin
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Yinlan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Dewei
authors.initials: D
authors.lastname: Ye
authors.affiliation: Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D019272:Leukocyte Elastase / Q000097:blood*; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000166:cytology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D000515:alpha 1-Antitrypsin / Q000097:blood*
chemical_list: D001786:Blood Glucose; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase
keywords: neutrophil elastase; nonalcoholic steatohepatitis; α1-antitrypsin