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Metabolomic Profiling for Histologically Fibrotic Stage in Chronic Drug-Induced Liver Injury

He, Xian, Zhou, Ming-Xi, Cheng, Cheng, Li, Shan-Shan, Gao, Yuan, Ma, Zhi-Tao, Song, Xin-Hua, Bai, Zhao-Fang, Zou, Zheng-Sheng, Xiao, Xiao-He, Wang, Jia-Bo, Lu, Ya-Wen·2022·Frontiers in Pharmacology
DOI 10.3389/fphar.2022.896198PMC PMC9163384
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Abstract

Background and aims: Chronic drug-induced liver injury (DILI) is a rare but under-researched adverse drug reaction–related disease, which is highly likely to progress into liver fibrosis and even cirrhosis. In this study, metabolomics was used to screen out characteristic metabolites related to the histological progression of fibrosis in chronic DILI and analyze the metabolic changes during the development of fibrosis to explain the underlying mechanism. Methods: Chronic DILI patients who underwent liver biopsy were divided into different fibrosis grades. Serum was analyzed by untargeted metabolomics to find serological characteristic metabolite fingerprints. The screened fingerprints were validated by the validation group patients, and the identification ability of fingerprints was compared using FibroScan. Results: A total of 31 metabolites associated with fibrosis and 11 metabolites associated with advanced fibrosis were identified. The validation group confirmed the accuracy of the two metabolite fingerprints [area under the curve (AUC) value 0.753 and 0.944]. In addition, the fingerprints showed the ability to distinguish the grades of fibrosis by comparing using FibroScan. The metabolite fingerprint pathway showed that bile acid synthesis is disturbed while lipid metabolism is extremely active, resulting in an overload of lipid metabolites in the occurrence and development of chronic DILI–associated fibrosis. Conclusions: Our metabolomic analysis reveals the unique metabolomic fingerprints associated with chronic DILI fibrosis, which have potential clinical diagnostic and prognostic significances. The metabolomic fingerprints suggest the disturbance of the lipid metabolites as the most important factor in the development of DILI fibrosis.

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Research works printed but not linked: 23

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Authors
He, X., Zhou, M.-X., Cheng, C., Li, S.-S., Gao, Y., Ma, Z.-T., Song, X.-H., Bai, Z.-F., Zou, Z.-S., Xiao, X.-H., Wang, J.-B., & Lu, Y.-W.
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2022-05-20
Volume
13
ISSN
1663-9812
DOI
10.3389/fphar.2022.896198
PMC
PMC9163384
Cited by
9
References
0
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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