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Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
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Drug-induced steatohepatitis.
Ajit Dash1, Robert A Figler1, Arun J Sanyal2
1a HemoShear Therapeutics LLC , Charlottesville , VA , USA.
Expert Opinion on Drug Metabolism & Toxicology
|October 21, 2016
Summary
Drug induced steatohepatitis (DISH) involves liver fat accumulation and inflammation. Advanced models and biomarkers are crucial for predicting and managing this drug-induced liver injury.
Area of Science:
- Hepatology
- Toxicology
- Drug Development
Background:
- Drug induced steatohepatitis (DISH) is a form of drug induced liver injury (DILI).
- It is characterized by lipid accumulation and inflammation in liver cells (hepatocytes).
- DISH shares pathological similarities with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
Purpose of the Study:
- To comprehensively review the mechanisms by which drugs cause DISH.
- To outline preclinical tools for predicting DISH and studying its pathways.
- To discuss clinical assessment and management strategies for DISH.
Main Methods:
- Review of existing literature on DISH mechanisms and preclinical models.
- Discussion of translational challenges in current models.
- Highlighting an organotypic liver system designed to overcome these hurdles.
Main Results:
- Various drugs can induce steatohepatitis through complex, interconnected pathways.
- Current preclinical models face translational limitations in predicting human DISH.
- Organotypic liver systems offer a more physiologically relevant context for drug evaluation.
Conclusions:
- Physiologically relevant preclinical models are essential for evaluating drug-induced steatohepatitis.
- Advanced organotypic models, biomarkers, and omics measurements can improve mechanistic understanding.
- These approaches may aid in predicting, detecting, and treating DISH, addressing an unmet clinical need.
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