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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Regulatory causality evaluation methods applied in kava hepatotoxicity: are they appropriate?
1Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Johann Wolfgang Goethe-University of Frankfurt/Main, Germany. rolf.teschke@gmx.de
Regulatory Toxicology and Pharmacology : RTP
|September 22, 2010
Summary
Regulatory causality assessments for kava hepatotoxicity often use liver-unspecific methods, leading to debate. Structured, quantitative, and liver-specific algorithms like CIOMS are recommended for accurate drug and herb safety evaluations.
Area of Science:
- Pharmacovigilance
- Hepatology
- Regulatory Science
Background:
- Kava (Piper methysticum G. Forster) use has been linked to liver injury since 1998, sparking regulatory and scientific debate on causality.
- Existing regulatory causality assessments for kava hepatotoxicity have faced criticism due to methodological limitations and data quality issues.
Purpose of the Study:
- To critically analyze regulatory causality assessment issues in suspected kava hepatotoxicity cases.
- To recommend strategies for minimizing regulatory risks in causality assessments for drug- and herb-induced liver injury.
Main Methods:
- Review of regulatory causality assessment approaches, including ad hoc evaluations, WHO scale, and Naranjo scale.
- Comparison of liver-unspecific methods with structured, quantitative, and liver-specific algorithms like CIOMS and main-test.
Main Results:
- Liver-unspecific causality assessment methods are unsuitable for evaluating drug- and herb-induced liver injury, including kava hepatotoxicity.
- Poor data quality combined with inappropriate assessment methods has led to flawed regulatory reassessments and scientific criticism.
Conclusions:
- Structured, quantitative, and liver-specific causality assessment algorithms (e.g., CIOMS) are superior for evaluating kava hepatotoxicity.
- Future regulatory standards should prioritize these specific methods to enhance the accuracy of liver injury causality assessments for drugs and herbs.
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