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| LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver |
| Zhong-Hua Wang a , Kenneth I Zheng b , Xiao-Dong Wang b , c , d , Jin Qiao e , Yang-Yang Li f , Li Zhang a , Ming-Hua Zheng b , c , d , Jian Wu a , g , h , ∗ |
a 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
b NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
c Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China
d The Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, China
e Department of General Practice, Huaihai Middle Road Community Health Service Center of Huangpu District, Shanghai 200025, China
f Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
g Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
h Laboratory of Fatty Liver and Metabolic Diseases, Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
∗ Corresponding author at: 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, 138 Yixue Yuan Road, P. O. Box 228, Shanghai 20 0 032, China.
E-mail address: jian.wu@fudan.edu.cn (J. Wu). |
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Abstract 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 stain- ing and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflam- mation, 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 phosphatidyl- choline (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 signifi- cantly 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 cor- relations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.
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2021, Vol. 20 
