Novac et al

Drug-induced liver injury (DILI) is the most common cause of acute liver failure and a leading cause of compound attrition in drug development. Deciphering the mechanism of drug hepatotoxicity remains a challenge. Whilst many in vitro and in vivo preclinical models have been developed for this purpose, all have their limitations. For example, inter-species differences in gene sequence or immunological response mean that animal models are not suitable for human-specific modalities, and simple in vitro models are not able to detect translationally relevant biomarkers.​

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Here, we assessed the potential of an in vitro human liver MPS, also known as an Liver-on-a-Chip, to accurately predict DILI risk for a wide range of compounds. To improve the translational relevance of this model, functional liver-specific endpoints were analyzed (including clinical biomarkers such as serum albumin and ALT). We assessed the sensitivity and selectivity of the model to predict DILI for a set of industry-standard compounds with known clinical DILI liabilities.