Computational Approaches for Drug-Induced Liver Injury (DILI) Prediction: State of the Art and Challenges

Drug-induced liver injury (DILI) is one of the prevailing causes of fulminant hepatic failure. It is estimated that three idiosyncratic drug reactions out of four result in liver transplantation or death. Additionally, DILI is the most common reason for withdrawal of an approved drug from the market. Therefore, the development of methods for the early identification of hepatotoxic drug candidates is of crucial importance. This review focuses on the current state of cheminformatics strategies being applied for the early in silico prediction of DILI. Herein, we discuss key issues associated with DILI modelling in terms of the data size, imbalance and quality, complexity of mechanisms, and the different levels of hepatotoxicity to model going from general hepatotoxicity to the molecular initiating events of DILI.