Metabolic Dysfunction-Associated Steatohepatitis Detected by Neutrophilic Crown-Like Structures in Morbidly Obese Patients:A Multicenter and Clinicopathological Study  

作　　者：Mengqi Fan Erfei Song Yuying Zhang Pengfei Zhang Bing Huang Kaixuan Yan Wah Yang Subrata Chakrabarti Hema Mahajan Sen Yan Ying Xu Shuang Hua Wei Liu Cunchuan Wang Aimin Xu Dewei Ye 

机构地区：[1]Key Laboratory of Metabolic Phenotyping in Model Animals,Guangdong Pharmaceutical University,Guangzhou,China [2]Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine,Guangdong Pharmaceutical University,Guangzhou,China [3]Department of Bariatric Surgery,The First Affiliated Hospital of Jinan University,Guangzhou,China [4]Department of Obstetrics,Shenzhen Longhua Maternity and Child Healthcare Hospital,Shenzhen,China [5]Department of Pathology and Laboratory Medicine,Western University,London,ON,Canada [6]Institute of Clinical Pathology and Medical Research,Pathology West,NSW Health Pathology,Sydney,NSW 2145,Australia [7]Dr.Everett Chalmers Hospital,Fredericton,NB,Canada [8]School of Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,China [9]The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,China [10]State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,Hong Kong,China [11]Department of Pharmacology and Pharmacy,The University of Hong Kong,Hong Kong,China [12]Department of Medicine,The University of Hong Kong,Hong Kong,China

出　　处：《Research》2025年第1期320-332,共13页研究(英文)

基　　金：financially supported by NSFC(82374171 and 81570701);the Natural Science Foundation of Guangdong Province(2024A1515012945);the Key Laboratory of Model Animal Phenotyping and Basic Research in Metabolic Diseases(2018KSYS003).

摘　　要：Metabolic dysfunction-associated steatohepatitis(MASH)is the progressive form of metabolic dysfunction-associated steatotic liver disease(MASLD),and closely associated with a high risk of liver-related morbidity and mortality.Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH,the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown.This clinicopathological study aimed to determine the association of neutrophilic crown-like structures(CLSs)in liver biopsies and evaluate their relevance to the histological diagnosis of MASH.A total of 483 morbidly obese adults who underwent bariatric surgery were recruited.Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3.All participants were classified into 4 histological subgroups:no MASLD(118,24.4%),MASLD(76,15.7%),borderline MASH(185,38.3%),and definite MASH(104,21.5%).In the discovery cohort(n=379),the frequency of neutrophilic CLSs increased in line with the severity of liver disease.The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH.At a cutoff value of<0.3 per 20×microscopic field,the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH;a cutoff at>1.3 per 20×microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups(no MASLD,MASLD,and borderline MASH).The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort(n=104).The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs.In conclusion,neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

关 键 词：hepatic neutrophils enhanced neutrophil infiltration neutrophilic crown structures morbidly obese clinicopathological study bariatric surgery 

分 类 号：R575.5[医药卫生—消化系统]