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Increased ratio of neutrophil elastase to α1‐antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis
Authors:Shufei Zang  Xiaojie Ma  Zhenjie Zhuang  Jing Liu  Dongxue Bian  Yunhao Xun  Qiuling Zhang  Falin Zhao  Wenjun Yang  Juan Liu  Yan Luo  Yinlan Liu  Bei Ye  Dewei Ye  Junping Shi
Affiliation:1. Department of Endocrinology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China;2. Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;3. Centre for Translational Medicine, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China;4. Department of Liver Diseases, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang, China;5. Department of Health Management, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China;6. Department of Pathology, Hangzhou Normal University Affiliated Hospital, Hangzhou, Zhejiang, China;7. Department of Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Abstract:An imbalance between neutrophil elastase (NE) and its inhibitor α1‐antitrypsin (A1AT) is known to contribute to the development of obesity‐related inflammation. This study aimed to investigate the role of the NE‐A1AT 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 A1AT 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‐A1AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1AT level with consequent NE/A1AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1AT, dating from the onset of NASH (NAS 3–4), and subsequently NE/A1AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut‐off of ?1459.43, NE/A1AT had a SEN of 88.8% and a SP of 83.3% with cut‐off of 0.363 to predict NASH. An increased NE: A1AT 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  α  1‐antitrypsin
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