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Updated: Jun 8, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques
Kaidi Guo1, Twan van den Beucken2
1Department of Toxicogenomics, GROW - Research Institute for Oncology & Reproduction, Maastricht University, Maastricht, 6200, MD, The Netherlands. k.guo@maastrichtuniversity.nl.
Abstract:
Drug-induced liver injury (DILI) refers to drug-mediated damage to the structure and function of the liver, ranging from mild elevation of liver enzymes to severe hepatic insufficiency, and in some cases, progressing to liver failure. The mechanisms and clinical symptoms of DILI are diverse due to the varying combination of drugs, making clinical treatment and prevention complex. DILI has significant public health implications and is the primary reason for post-marketing drug withdrawals. The search for reliable preclinical models and validated biomarkers to predict and investigate DILI can contribute to a more comprehensive understanding of adverse effects and drug safety. In this review, we examine the progress of research on DILI, enumerate in vitro models with potential benefits, and highlight cellular molecular perturbations that may serve as biomarkers. Additionally, we discuss omics approaches frequently used to gather comprehensive datasets on molecular events in response to drug exposure. Finally, three commonly used gene modulation techniques are described, highlighting their application in identifying causal relationships in DILI. Altogether, this review provides a thorough overview of ongoing work and approaches in the field of DILI.
Insights
Drug-induced liver injury (DILI) is complex liver damage from medications. This review explores preclinical models, biomarkers, and omics approaches to improve drug safety and DILI understanding.
Area of Science:
- Pharmacology
- Toxicology
- Hepatology
Background:
- Drug-induced liver injury (DILI) is a significant cause of liver damage and drug withdrawals.
- Diverse mechanisms and symptoms complicate DILI treatment and prevention.
- Reliable preclinical models and biomarkers are crucial for understanding DILI and enhancing drug safety.
Purpose of the Study:
- To review current research on DILI.
- To identify promising in vitro models and potential biomarkers for DILI.
- To discuss omics approaches and gene modulation techniques for DILI research.
Main Methods:
- Literature review of DILI research.
- Enumeration of in vitro models.
- Highlighting cellular molecular perturbations as biomarkers.
- Discussion of omics approaches (genomics, proteomics, metabolomics).
- Description of gene modulation techniques (e.g., CRISPR-Cas9).
Main Results:
- Progress in DILI research is reviewed.
- In vitro models show potential for DILI investigation.
- Cellular molecular perturbations are identified as potential biomarkers.
- Omics approaches provide comprehensive molecular event datasets.
- Gene modulation techniques aid in establishing causal relationships.
Conclusions:
- This review offers a comprehensive overview of DILI research.
- Advances in preclinical models, biomarkers, and omics are vital for drug safety.
- Gene modulation techniques enhance the understanding of DILI mechanisms.
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