Abstract: Drug-induced liver injury (DILI) is a major cause of drug failure in clinical trial and market withdrawal. Animal models are utilized to predict the risk of drug-induced liver injury. However, due to species differences, the accuracy of animal models is poor. Multiple human-derived hepatotoxic prediction models have been developed to assess this potential risk. This article reviews commonly used in vitro hepatotoxic models, as well as the latest improvement of hepatocyte culture protocols, especially hepatic co-culture system and 3D culture system in order to improve the accuracy of hepatotoxic risk prediction, which may also guide the liver toxicity mechanistic investigation in clinic. 

Key words: hepatotoxicity, drug-induced liver injury, alternative models of liver