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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
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Drug-induced liver injury
Michael D Leise1, John J Poterucha1, Jayant A Talwalkar1
1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Mayo Clinic Proceedings
|January 7, 2014
Summary
Idiosyncratic drug-induced liver injury (DILI) affects 20 per 100,000 annually. Risk factors include dose, lipophilicity, and metabolism, with genetic predisposition playing a role in some cases.
Area of Science:
- Hepatology
- Pharmacology
- Toxicology
Background:
- Drug-induced liver injury (DILI) is a significant clinical concern, categorized as predictable (nonidiosyncratic) or unpredictable (idiosyncratic).
- Idiosyncratic DILI represents a substantial portion of acute liver failure cases and has an estimated incidence of 20 new cases per 100,000 individuals annually.
- Understanding risk factors and diagnostic approaches for DILI is crucial for patient management.
Purpose of the Study:
- To review current epidemiologic data and risk factors associated with idiosyncratic drug-induced liver injury (DILI).
- To discuss the categorization, diagnosis, and management of DILI, including common causative agents and prognostic indicators.
- To highlight emerging biomarkers and new drug classes implicated in DILI.
Main Methods:
- Systematic literature review using PubMed with terms 'drug induced liver injury' OR DILI, filtered for English language and human studies from January 1, 2000, onwards.
- Inclusion of manually searched bibliographies from key references and seminal works predating 2000.
- Analysis of new epidemiologic data, risk factors, diagnostic criteria, common culprits, and novel therapeutic and diagnostic developments in DILI.
Main Results:
- Idiosyncratic DILI incidence is approximately 20 per 100,000 persons annually, accounting for 11% of acute liver failure in the US.
- Key risk factors identified include medication dose, drug lipophilicity, and hepatic metabolism; genetic predisposition is a significant factor for specific drugs.
- Common DILI causes include amoxicillin/clavulanate, isoniazid, and NSAIDs; drug discontinuation improves outcomes, though high bilirubin levels portend mortality.
Conclusions:
- Idiosyncratic DILI is a significant health issue with identifiable risk factors and common etiologies.
- Accurate categorization (hepatitic, cholestatic, mixed) and exclusion of other liver diseases are vital for diagnosis.
- Emerging biomarkers and ongoing research into new drug classes offer promise for improved DILI detection and management.
Keywords:
AIHALFALTCNSDI-AIHDILIDILINDrug Induced Liver Injury NetworkFDAFood and Drug AdministrationHDSHEVHLAIVLTxN-AcetylcysteineNACNAFLDTNFULNacute liver failurealanine aminotransferaseautoimmunelike hepatitiscentral nervous systemdrug-induced autoimmunelike hepatitisdrug-induced liver injuryhepatitis E virusherbal and dietary supplementhuman leukocyte antigenintravenousliver transplantationmiRNAmicro RNAnonalcoholic fatty liver diseasetumor necrosis factorupper limit of normal
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