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The potential of cytokines as safety biomarkers for drug-induced liver injury

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Abstract

Drug-induced liver injury (DILI) is an event that has a detrimental impact on drug development and patient safety; therefore the identification of novel biomarkers that are both sensitive and specific to the liver would have great benefit. Inflammation is known to be associated with human cases of DILI, and given the role of cytokines in modulating the inflammatory response, changes in cytokine expression patterns certainly show promise as potential biomarkers of DILI. Cytokines are interesting candidates for novel biomarkers as they are relatively accessible (by blood sampling) and accurately quantifiable. In particular, recent interest has developed in mechanism-specific, rather than tissue-specific, biomarkers. However, without fully understanding the role of inflammation in DILI and the role of cytokines in modulating the inflammatory response, cytokines may be limited in their use, being either diagnostic of the type of injury that has occurred and/or prognostic of outcome (recovery from DILI, cirrhosis, acute liver failure). Intracellular components released by damaged hepatocytes, although inaccessible and currently difficult to quantify, may be better biomarkers for the prognosis of severity of injury. In both cases there is a pressing need for the development and validation of assays sensitive enough and with a sufficient dynamic range to detect changes upon drug treatment. Although promising candidates are appearing in the literature, much remains to be done to understand the role of inflammation in DILI and the role that a given cytokine has in the inflammatory cascade associated with DILI before cytokines are viewed as biomarkers for DILI.

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Acknowledgements

The authors would like to acknowledge the support provided by the Medical Research Council for the Centre of Drug Safety Science (Grant Number: G0700654), Association of the British Pharmaceutical Industry and British Toxicological Society.

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  1. MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, University of Liverpool, Liverpool, UK, L69 3GE

    Hugh G. Laverty, Daniel J. Antoine, Craig Benson, Masautso Chaponda, Dominic Williams & B. Kevin Park

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Laverty, H.G., Antoine, D.J., Benson, C. et al. The potential of cytokines as safety biomarkers for drug-induced liver injury. Eur J Clin Pharmacol 66, 961–976 (2010). https://doi.org/10.1007/s00228-010-0862-x

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