Metabolic Dysfunction-Associated Steatohepatitis Detected by Neutrophilic Crown-Like Structures in Morbidly Obese Patients: A Multicenter and Clinicopathological Study
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
Affiliations
Mengqi Fan
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
Erfei Song
Department of Bariatric Surgery,
The First Affiliated Hospital of Jinan University, Guangzhou, China.
Yuying Zhang
Department of Obstetrics, Shenzhen Longhua Maternity and Child Healthcare Hospital, Shenzhen, China.
Pengfei Zhang
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
Bing Huang
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
Kaixuan Yan
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
Wah Yang
Department of Bariatric Surgery,
The First Affiliated Hospital of Jinan University, Guangzhou, China.
Subrata Chakrabarti
Department of Pathology and Laboratory Medicine,
Western University, London, ON, Canada.
Hema Mahajan
Institute of Clinical Pathology and Medical Research,
Pathology West, NSW Health Pathology, Sydney, NSW 2145, Australia.
Sen Yan
Dr. Everett Chalmers Hospital, Fredericton, NB, Canada.
Ying Xu
School of Chinese Medicine,
Guangdong Pharmaceutical University, Guangzhou, China.
Shuang Hua
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
Wei Liu
The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Cunchuan Wang
Department of Bariatric Surgery,
The First Affiliated Hospital of Jinan University, Guangzhou, China.
Aimin Xu
State Key Laboratory of Pharmaceutical Biotechnology,
The University of Hong Kong, Hong Kong, China.
Dewei Ye
Key Laboratory of Metabolic Phenotyping in Model Animals,
Guangdong Pharmaceutical University, Guangzhou, China.
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 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.
