The Liver Toxicity Knowledge Base (LKTB) and drug-induced liver injury (DILI) classification for assessment of human liver injury

Abstract

Drug-induced liver injury (DILI) is challenging for drug development, clinical practice and regulation. The Liver Toxicity Knowledge Base (LTKB) provides essential data for DILI study. Areas covered: The LTKB provided various types of data that can be used to assess and predict DILI. Among much information available, several reference drug lists with annotated human DILI risk are of important. The LTKB DILI classification data include DILI severity concern determined by the FDA drug labeling, DILI severity score from the NIH LiverTox database, and other DILI classification schemes from the literature. Overall, ~1000 drugs were annotated with at least one classification scheme, of which around 750 drugs were flagged for some degree of DILI risk. Expert commentary: The LTKB provides a centralized repository of information for DILI study and predictive model development. The DILI classification data in LTKB could be a useful resource for developing biomarkers, predictive models and assessing data from emerging technologies such as in silico, high-throughput and high-content screening methodologies. In coming years, streamlining the prediction process by including DILI predictive models for both DILI severity and types in LTKB would enhance the identification of compounds with the DILI potential earlier in drug development and risk assessment.

Keywords: DILI; Drug-Induced Liver Injury; LTKB; Liver Toxicity Knowledgebase; computational toxicology; drug classification for DILI; human liver injury.