Drug Metabolism and Drug-Induced Liver Injury

Dear Colleagues,

Idiosyncratic drug-induced liver injury (iDILI) represents one of the most cited toxicities associated with medications including small molecules and biologics. Managing DILI is a big challenge for clinicians, industries, and regulatory agencies. iDILI is an unpredictable adverse effect as it only occurs in a small portion of patients. The mechanism of iDILI is extremely complex and complicated. The adaptive immune system can mediate most iDILI cases, but the triggering factors remain unclear. Previous studies revealed a connection between metabolism and drugs commonly causing iDILI with causality. The lack of an animal model of iDILI that can mimic human iDILI means that mechanistic studies are urgently needed. Our current understanding of the mechanistic steps leading to injury is particularly fragmentary.

Understanding the mechanism underlying iDILI will allow us to predict, prevent, and manage toxicity. This Special Issue invites original research and review articles addressing the pathogenesis, underlying mechanisms, new tools for investigating drug metabolism and DILI, and the in silico prediction of drug metabolism and iDILI.

The topics of this Special Issue include but are not limited to:

1. Mechanistic studies on the drug metabolism and toxicity originating from drug metabolizing enzymes and transporters (e.g., P450s);
2. Factors influencing drug metabolism, pharmacokinetic drug–drug interactions, and the risk of DILI (e.g., genetic susceptibility, and environmental factors) in DILI;
3. Regulation of drug metabolizing enzymes and transporters in DILI (e.g., induction or inhibition);
4. Gut microbiome in drug metabolism and DILI;
5. Biomarker of DILI;
6. Novel tools (e.g., metabolomics, mass spectrometry imaging) and in vitro and in vivo models (e.g., 3D organoids, liver humanized mouse model) in the drug metabolism and DILI;
7. In silico prediction and artificial intelligence for drug metabolism and toxicity;
8. Influence of intra- and inter-species differences in drug metabolism and toxicity.

Dr. Feng Li
Guest Editor

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