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

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

DOI:
10.1016/j.hbpd.2021.05.008
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发表时间:
2021-10-08
影响因子:
3.3
通讯作者:
Wu, Jian
Wu, Jian
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Zhong-Hua;Zheng, Kenneth, I;Wu, Jian

文献摘要

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背景:非酒精性脂肪肝病(NAFLD)是主要肝病之一,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)。但是,在临床实践中将NASH与NAFL区分开来,没有可靠的非侵入性参数。本研究是找到一种非侵入性方法来通过脂质组分析区分这两类NAFLD。方法:使用脂质组分析来确定20名NAFL和10名NASH肝活检患者血液中脂质部分的变化。苏木精和曙红染色和Masson的三色染色后,评估了肝组织学。分析了与脂肪代谢物与脂肪变性,炎症,肝细胞坏死,纤维化和NAFLD活性评分(NAS)相关的曲线。结果:与NAFL患者相比,NASH患者的脂肪变性程度更高,气囊变性,小叶炎症。总共确定了434个不同的脂质分子,这些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:D14: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组的组相比。具体分析表明,总体脂肪组概况从NAFL转移到NASH,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)(26:1) /11:0)]或浆元[PC(O-22:0/0:0),PC(O-18:0/0:0),PC(O-16:0/0:0)],哪个NASH患者发生了显着改变。此外,PC(14:0/18:2),磷酸酸(18:2/24:4)与NAS正相关;而PC(18:0/0:0)与纤维化评分正相关。结论:本研究揭示了从NAFL到NASH的总体脂肪组概况转移,确定了有价值的脂质部分,这些脂质部分可能是NAFLD分类中非侵入性生物标志物。脂质部分与NAS和NAS的相关性以及纤维化评分表明,这些脂质生物标志物可用于预测疾病的严重程度。 (c)2021年中国省大学医学院第一家附属医院。由Elsevier B.V.保留所有权利。
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. (c) 2021 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.