LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver  

作　　者：Zhong-Hua Wang Kenneth I Zheng Xiao-Dong Wang Jin Qiao Yang-Yang Li Li Zhang Ming-Hua Zheng Jian Wu 

机构地区：[1]Department of Medical Microbiology and Parasitology,MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology,School of Basic Medical Sciences,Fudan University Shanghai Medical College,Shanghai 200032,China [2]NAFLD Research Center,Department of Hepatology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China [3]Institute of Hepatology,Wenzhou Medical University,Wenzhou 325000,China [4]The Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province,Wenzhou 325000,China [5]Department of General Practice,Huaihai Middle Road Community Health Service Center of Huangpu District,Shanghai 200025,China [6]Department of Pathology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China [7]Department of Gastroenterology and Hepatology,Zhongshan Hospital of Fudan University,Shanghai 200032,China [8]Laboratory of Fatty Liver and Metabolic Diseases,Shanghai Institute of Liver Diseases,Fudan University Shanghai Medical College,Shanghai 200032,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2021年第5期452-459,共8页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the Ministry of Science&Technology of China(2016YFE0107400);the National Natural Science Foundation of China(81272436,81572356,81871997,81500665 and 82070588);High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032);Project of New Century 551 Talent Nurturing in Wenzhou。

摘　　要：Background: Nonalcoholic fatty liver disease(NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver(NAFL) and nonalcoholic steatohepatitis(NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score(NAS) was analyzed. Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine(PC)(P-22:0/18:1), sphingomyelin(SM)(d14:0/18:0), SM(d14:0/24:0), SM(d14:0/22:0), phosphatidylethanolamine(PE)(18:0/22:5), PC(O-22:2/12:0), and PC(26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC(14:0/18:2), PE(18:0/22:5) and PC(26:1/11:0)] or plasmalogens [PC(O-22:0/0:0), PC(O-18:0/0:0), PC(O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC(14:0/18:2), phosphatidic acid(18:2/24:4) were positively correlated with NAS;whereas PC(18:0/0:0) was correlated positively with fibrosis score. Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieti

关 键 词：LIPIDOMICS Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease BIOMARKER Nonalcoholic activity score Hepatic fibrosis 

分 类 号：R575.5[医药卫生—消化系统]