Exploring Individual Variability in Drug-Induced Liver Injury (DILI) Responses through Metabolomic Analysis.

Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization.

The assessment of the potential hepatotoxicity of new drugs by metabolomics.

Drug hepatotoxicity assessment is a relevant issue both in the course of drug development as well as in the post marketing phase. The use of human relevant models in combination with powerful analytical methods (metabolomic analysis) is a promising approach to anticipate, as well as to understand and investigate the effects and mechanisms of drug hepatotoxicity in man. The metabolic profile analysis of biological liver models treated with hepatotoxins, as compared to that of those treated with non-hepatotoxic compounds, provides useful information for identifying disturbed cellular metabolic reactions, pathways, and networks.

Metabolomics-based strategy to assess drug hepatotoxicity and uncover the mechanisms of hepatotoxicity involved.

Toxicity studies, among them hepatotoxicity, are key throughout preclinical stages of drug development to minimise undesired toxic effects that might eventually appear in the course of the clinical use of the new drug. Understanding the mechanism of injury of hepatotoxins is essential to efficiently anticipate their potential risk of toxicity in humans. The use of in vitro models and particularly cultured hepatocytes represents an easy and robust alternative to animal drug hepatotoxicity testing for predicting human risk.