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代谢组学分析与药物性肝损伤诊断生物标志物探寻：一项横断面队列研究

Metabolomics Profiling and Diagnosis Biomarkers Searching for Drug-Induced Liver Injury Implicated to : A Cross-Sectional Cohort Study.

作者信息

Huang Ying, Zhao Xu, Zhang Zi-Teng, Chen Shuai-Shuai, Li Shan-Shan, Shi Zhuo, Jing Jing, Huang Ang, Guo Yu-Ming, Bai Zhao-Fang, Zou Zheng-Sheng, Xiao Xiao-He, Wang Jia-Bo, Niu Ming

机构信息

College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.

China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

出版信息

Front Med (Lausanne). 2020 Nov 30;7:592434. doi: 10.3389/fmed.2020.592434. eCollection 2020.

DOI:10.3389/fmed.2020.592434
PMID:33330552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7734208/
Abstract

The diagnosis of drug-induced liver injury (DILI) remains a challenge and the cases of Thunb. (PM) induced DILI (PM-DILI) have received much attention This study aimed to identify a simple and high-efficiency approach to PM-DILI diagnosis via metabolomics analysis. Plasma metabolites in 13 PM-DILI patients were profiled by liquid chromatography along with high-resolution mass spectrometry. Meanwhile, the metabolic characteristics of the PM-DILI were compared with that of autoimmune hepatitis (AIH), hepatitis B (HBV), and healthy volunteers. Twenty-four metabolites were identified to present significantly different levels in PM-DILI patients compared with HBV and AIH groups. These metabolites were enriched into glucose, amino acids, and sphingolipids metabolisms. Among these essential metabolites, the ratios of P-cresol sulfate vs. phenylalanine and inosine vs. bilirubin were further selected using a stepwise decision tree to construct a classification model in order to differentiate PM-DILI from HBV and AIH. The model was highly effective with sensitivity of 92.3% and specificity of 88.9%. This study presents an integrated view of the metabolic features of PM-DILI induced by herbal medicine, and the four-metabolite decision tree technique imparts a potent tool in clinical diagnosis.

摘要

药物性肝损伤（DILI）的诊断仍然是一项挑战，雷公藤（PM）所致DILI（PM-DILI）的病例备受关注。本研究旨在通过代谢组学分析确定一种简单高效的PM-DILI诊断方法。采用液相色谱-高分辨率质谱联用技术对13例PM-DILI患者的血浆代谢物进行分析。同时，将PM-DILI的代谢特征与自身免疫性肝炎（AIH）、乙型肝炎（HBV）及健康志愿者进行比较。与HBV和AIH组相比，共鉴定出24种在PM-DILI患者中水平有显著差异的代谢物。这些代谢物主要富集在葡萄糖、氨基酸和鞘脂代谢途径中。在这些关键代谢物中，进一步利用逐步决策树选择对甲酚硫酸盐与苯丙氨酸的比值以及肌苷与胆红素的比值构建分类模型，以区分PM-DILI与HBV和AIH。该模型具有高效性，灵敏度为92.3%，特异性为88.9%。本研究展示了草药诱导的PM-DILI的代谢特征全貌，四代谢物决策树技术为临床诊断提供了有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3924/7734208/6f763393eff3/fmed-07-592434-g0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3924/7734208/8cac48d87503/fmed-07-592434-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3924/7734208/ab8f6941e951/fmed-07-592434-g0003.jpg
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