Perspectives on the Regulatory and Clinical Science of Drug-Induced Liver Injury (DILI)

  • Mark I. AviganEmail author
  • Monica A. Muñoz
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


This chapter provides a regulatory framework of drug-induced liver injury (DILI) risk assessment, whose foundation is the understanding, identification, and evaluation of different forms of hepatotoxicity caused by a drug or biological agent. Regulatory scientists strive to translate evolving knowledge into an accurate and efficient prediction of DILI risk in humans as early as possible in a product’s life cycle. In addition, better characterization of factors that underlie individual susceptibility can lead to improved risk minimization, and ultimately enhance the balance between treatment-associated benefits and risks. Heightened DILI risk plays a critical role in the trajectory of approval for a therapeutic product. Compound development may be terminated when a signal of potentially serious DILI emerges given the theoretical risks to trial subjects and potential opportunity cost that may be incurred. The limitations of currently available analytical tools to quantify DILI risk undoubtedly have resulted in the premature discontinuation of compounds that ultimately may have been associated with negligible or acceptable levels of risk for the intended treatment population. For other compounds, an associated DILI risk may go unrecognized in the premarket setting, and only shows an unacceptable benefit–risk balance in the postmarketing setting. No drug or biological agent has been withdrawn in the US market following approval due to hepatotoxicity since the publication of the FDA Guidance for Industry on DILI Premarketing Clinical Evaluation in 2009. Nonetheless, some recently approved agents have been linked to an increased risk for DILI in vulnerable patients, resulting in the inclusion of Boxed Warnings or Warnings of hepatotoxicity in several of their product labels.

Key words

Drug-induced liver injury Hepatotoxicity Clinical trials Risk–benefit Surveillance 



The views expressed are those of the authors and do not necessarily represent the position of, nor imply an endorsement from, the US Food and Drug Administration or the US Government.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Office of Surveillance and Epidemiology, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringUSA

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