LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver,Hepatobiliary & Pancreatic Diseases International

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LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver
Hepatobiliary & Pancreatic Diseases International ( IF 3.6 ) Pub Date : 2021-06-25 , DOI: 10.1016/j.hbpd.2021.05.008
Zhong-Hua Wang ₁ , Kenneth I Zheng ₂ , Xiao-Dong Wang ₃ , Jin Qiao ₄ , Yang-Yang Li ₅ , Li Zhang ₁ , Ming-Hua Zheng ₃ , Jian Wu ₆

Affiliation

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.
NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China; The Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325000, China.
Department of General Practice, Huaihai Middle Road Community Health Service Center of Huangpu District, Shanghai 200025, China.
Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
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; Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Laboratory of Fatty Liver and Metabolic Diseases, Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China.

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 moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

中文翻译：

基于 LC-MS 的脂质组学分析区分非酒精性脂肪性肝炎和非酒精性脂肪肝

背景

非酒精性脂肪性肝病（NAFLD）是主要的肝脏疾病之一，其病理特征包括非酒精性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH）。然而，在临床实践中没有可靠的非侵入性参数来区分 NASH 和 NAFL。本研究旨在通过脂质组学分析找到一种非侵入性方法来区分这两类 NAFLD。

方法

脂质组学分析用于确定 20 名 NAFL 和 10 名 NASH 患者的肝活检血液中脂质部分的变化。在苏木精和伊红染色和马森三色染色后评估肝组织学。分析了与脂肪变性、炎症、肝细胞坏死性凋亡、纤维化和 NAFLD 活动评分 (NAS) 相关的脂质代谢物谱。

结果

与NAFL患者相比，NASH患者脂肪变性、气球样变性、小叶炎症程度更高。共鉴定出434种不同的脂质分子，主要由各种磷脂和三酰基甘油组成。许多脂质，例如磷脂酰胆碱 (PC) (P-22:0/18:1)、鞘磷脂 (SM) (d14:0/18:0)、SM (d14:0/24:0)、SM (d14: 0/22:0)、磷脂酰乙醇胺 (PE) (18:0/22:5)、PC (O-22:2/12:0) 和 PC (26:1/11:0) 在 NASH 中升高组与 NAFL 组相比。具体分析揭示了从 NAFL 到 NASH 的总体脂质组学转变，并确定了有价值的脂质部分，例如 PC [PC (14:0/18:2)、PE (18:0/22:5) 和 PC (26:1 /11:0)] 或缩醛磷脂 [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)]，其中在 NASH 患者中显着改变。此外，个人电脑（14：0/18:2)、磷脂酸(18:2/24:4)与NAS呈正相关；而 PC (18:0/0:0) 与纤维化评分呈正相关。