Biomarkers for drug-induced liver injury

Abstract

Of the estimated 10,000 documented human drugs, more than 1000 have been associated with drug-induced liver injury (DILI), although causality has not always been established clearly. Numerous biomarkers for DILI have been explored, but less than ten are adopted or qualified as valid by the US FDA. The biomarkers for DILI are individual or a panel of proteins, nucleic acids or metabolites from various sources, such as the liver, blood and urine. While most DILI biomarkers are drug independent, some possibly ‘drug-specific’ DILIs have been explored, but specificity and sensitivity of both types need to be improved for the diagnosis of DILI during drug development and in clinical practice. Novel approaches for DILI biomarkers have been actively investigated recently, but produced mainly animal-based biomarkers, which are possibly useful for drug development, but are not suitable or have not been validated for clinical applications. This review summarizes the current practice and future perspectives for DILI biomarkers.

Keywords::

• biomarker
• drug-induced liver injury
• genomics
• hepatotoxicity
• idiosyncratic

Financial & competing interests disclosure

This project is supported by the US FDA's Critical Path program, Office of Women's Health and Chief Scientist Challenge Grant. Dr Qiang Shi is supported by the Research Participation Program at the NCTR administrated by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US FDA. The views presented in this article do not necessarily reflect those of the US FDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.