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Host Risk Modifiers in Idiosyncratic Drug-Induced Liver Injury (DILI) and Its Interplay with Drug Properties

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Drug-Induced Liver Toxicity

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Idiosyncratic drug-induced liver injury (DILI) occurs in a small proportion of individuals exposed to a drug and is unpredictable based on the drug’s pharmacological action and ingested dose. Due to the multifactorial pathology of this condition various factors associated with both the drug and the patient can affect DILI susceptibility and clinical presentation. A major challenge in the area of DILI is therefore to determine these risk factors and their interactions in order to predict individuals at risk of developing DILI. This would enable patients without significant DILI risk to securely benefit from an effective treatment (including medications with black box warnings for hepatotoxicity), while ensuring patient safety to those at increased risk by providing an alternative medication. Host-related DILI modifiers proposed to date include age, sex, genetic variations, associated conditions, concomitant medications and lifestyle. In addition, physicochemical and toxicological drug properties such as dose, lipophilicity, reactive metabolite formation, mitochondrial liability, and transporter inhibition are likewise assumed to have a potential modulating effect on DILI. Individually none of these host and drug-related features are likely to be sufficient to induce liver injury, but when combined could lead to DILI development. Hence, considering interactions between DILI host and drug factors could be more useful in predicting individuals at increased risk of developing DILI. In this chapter we provide an overview of the current understanding of risk factors for idiosyncratic DILI.

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Authors and Affiliations

  1. Unidad de Gestión de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain

    Camilla Stephens, M. Isabel Lucena & Raúl J. Andrade

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  1. Camilla Stephens
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  2. M. Isabel Lucena
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  3. Raúl J. Andrade
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Correspondence to Raúl J. Andrade .

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Editors and Affiliations

  1. Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA

    Minjun Chen

  2. Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA

    Yvonne Will

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Stephens, C., Lucena, M.I., Andrade, R.J. (2018). Host Risk Modifiers in Idiosyncratic Drug-Induced Liver Injury (DILI) and Its Interplay with Drug Properties. In: Chen, M., Will, Y. (eds) Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-7677-5_23

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  • DOI: https://doi.org/10.1007/978-1-4939-7677-5_23

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  • Publisher Name: Humana, New York, NY

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  • Online ISBN: 978-1-4939-7677-5

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