Idiosyncratic drug-induced liver injury (DILI) is a rare adverse drug reaction resulting in liver injury, and a cause of failure in both clinical and post-approval stages of drug development. Predictive the toxicity of new chemicals entities (NCE) is a key challenge to the pharmaceutical industry (FDA, 2009). In order to avoid the use of laboratory animals, and to reduce the cost of pre clinical studies, in vitro toxicology combined the use of cellular models with the measurements of several cell health endpoints in order to predict the hepatotoxicity of NCE. Primary Human Hepatocytes and heptocyte-like cell lines such as HepaRG, Upcytes and HepG2 are commonly used in NCE safety assessment. However, standard cellular assays have shown their limitation to specifically predict DILI potential of NCE (Sison-Young et al., 2017). The era of high content analysis, and especially phenotypic screening, bring new strategy for toxicologist to predict DILIs and their underlying mechanisms, and provides an effective means to reduce drug development failures due to insufficient safety (Xu, 2015).
- FDA (2009). Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation.
- Sison-Young, R.L., Lauschke, V.M., Johann, E., Alexandre, E., Antherieu, S., Aerts, H., Gerets, H.H.J., Labbe, G., Hoët, D., Dorau, M., et al. (2017). A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch. Toxicol. 91, 1385–1400.
- Xu, J.J. (2015). Cellular imaging: a key phenotypic screening strategy for predictive toxicology. Front. Pharmacol. 6.