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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
1Department of Medicine, Brighton and Sussex Medical School, and Department of Gastroenterology and Hepatology, Brighton and University Hospital, Brighton, UK.
Clinical Medicine (London, England)
|December 14, 2016
Summary
Drug-induced liver injury (DILI) is a leading cause of acute liver failure (ALF). Early recognition and drug withdrawal are crucial for managing idiosyncratic DILI, with liver transplant considered for severe cases.
Area of Science:
- Hepatology
- Clinical Pharmacology
- Immunogenetics
Background:
- Drug-induced liver injury (DILI) is the primary cause of acute liver failure (ALF) in Western countries.
- Idiosyncratic DILI, often immune-mediated and linked to human leukocyte antigen variants, affects a small subset of patients.
- Diagnosis relies on high suspicion and exclusion of other liver disease causes due to lack of specific biomarkers.
Purpose of the Study:
- To review the current understanding of idiosyncratic drug-induced liver injury.
- To highlight diagnostic challenges and management strategies for DILI.
- To emphasize the importance of early intervention and liver transplantation in severe cases.
Main Methods:
- Literature review of drug-induced liver injury, focusing on idiosyncratic reactions.
- Analysis of common drug classes and supplements associated with DILI.
- Discussion of diagnostic criteria, risk factors, and treatment approaches for DILI and ALF.
Main Results:
- Antibiotics are the most frequent culprits of idiosyncratic DILI, with herbal and dietary supplements emerging as significant causes.
- Elevated transaminases (AST/ALT ratio ≥5) and jaundice necessitate prompt discontinuation of the suspected agent.
- Hepatocellular DILI and female gender are risk factors for ALF; N-acetylcysteine may offer early benefit.
Conclusions:
- Prompt drug withdrawal is essential upon DILI diagnosis, particularly with significant liver enzyme elevation or jaundice.
- Management is primarily supportive, with liver transplantation a critical consideration due to poor transplant-free survival in severe idiosyncratic DILI.
- Increased awareness of DILI from both pharmaceuticals and supplements is vital for patient safety.
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