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

ABSTRACT

Introduction: 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:

• Drug-Induced Liver Injury
• DILI
• drug classification for DILI
• human liver injury
• Liver Toxicity Knowledgebase
• LTKB
• computational toxicology

Disclaimer

The views presented in this article do not necessarily reflect current or future opinion or policy of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification and not intended as endorsement.

Disclosure of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was supported by the National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR.