Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis
10.16438/j.0513-4870.2018-1059
- VernacularTitle:慢性药物性肝损伤相关肝硬化的代谢组学诊断标志物研究
- Author:
Lu-ge WEI
1
,
2
;
Xiao-hui WANG
3
;
Ming NIU
3
;
Xiao-yi LIU
3
;
Can TU
3
;
Yuan-yuan ZHOU
3
;
Huang-wan-yin HU
3
;
Ya-ming ZHANG
3
;
Hui-fang LI
1
;
Zheng-sheng ZOU
4
;
Xiao-he XIAO
5
;
Jia-bo WANG
3
Author Information
1. Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, China
2. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
3. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
4. Treatment and Research Center for Non-infectious Liver Diseases, 302 Military Hospital, Beijing 100039, China
5. Integrative Medicine Center, 302 Military Hospital, Beijing 100039, China
- Publication Type:Research Article
- Keywords:
rug-induced liver injury;
chronicity;
liver cirrhosis;
metabolomics;
iagnosis;
biomarker
- From:
Acta Pharmaceutica Sinica
2019;54(8):1449-1456
- CountryChina
- Language:Chinese
-
Abstract:
About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.
