Holistic metabolomic profiling of chronic versus acute drug-induced liver injury
image: DILI, drug-induced liver injury; TCP, tentative cut-off point.
Credit: Yuecheng Yu, Jiabo Wang
Background and Objectives
Drug-induced liver injury (DILI) can present as a chronic phenotype or acute course. However, there is a lack of research on the underlying mechanisms of chronic DILI as well as the definition of cut-off point. We aimed to profile holistic metabolic characteristics of chronic DILI and provide evidence for the cut-off point by serum metabolomics.
Methods
The sera of DILI patients were divided into Group I (0–6 months), Group II (6–12 months), and Group III (>12 months) based on the duration of liver injury. In total, 2,105 metabolites associated with the DILI duration were screened out as the holistic metabolomic signature (HMS). By unsupervised principal component analysis on the HMS dataset, the samples spontaneously represented a two-cluster pattern of the three groups, i.e., Group I as the first cluster and Group II/III as the second cluster, which suggested six months as the potential metabolomic cut-off point of DILI chronicity. Then, the differentiation ability of the metabolomic signature was validated in an independent cohort. We further screened out 23 most-associated metabolites as the metabolic fingerprint (MFP) for the DILI duration and constructed an eigenmetabolite by dimension reduction.
Results
The eigenmetabolite was significantly different in chronic versus acute DILI and was not related to the severity grade of liver injury. Pathway enrichment analysis underlined the enhanced metabolic pathways of lipids in chronic DILI, which are associated with energy metabolism remodeling and immune regulation balance.
Conclusions
MFP was different between chronic and acute DILI. Six months might be the potential metabolomic cut-off point in defining chronicity of DILI.
Full text:
https://www.xiahepublishing.com/2835-6357/FIM-2022-00057
The study was recently published in the Future Integrative Medicine.
Future Integrative Medicine (FIM) publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.
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