Drug-induced liver injury

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Abstract

Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. These risk factors modify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell death, activation of an adaptive immune response and a failure to adapt, with progression to overt liver injury. Idiosyncratic DILI is a relative rare hepatic disorder but can be severe and, in some cases, fatal, presenting with a variety of phenotypes, which mimic other hepatic diseases. The diagnosis of DILI relies on the exclusion of other aetiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients with cancer.

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Fig. 1: Hepatocyte transporters and cellular mechanisms of DILI.
Fig. 2: Molecular mechanisms of idiosyncratic and intrinsic DILI.
Fig. 3: Proposed algorithm to suspect, diagnose and manage idiosyncratic DILI.
Fig. 4: Traditional and investigational biomarkers of DILI.
Fig. 5: Proposed detection and management of hepatotoxicity due to ICIs in patients with cancer.

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Acknowledgements

We acknowledge the support of the European Cooperation in Science & Technology (COST) Action CA17112 Prospective European Drug-Induced Liver Injury Network. R.J.A., N.C., E.S.B., A.S., G.A.K.-U, H.D., M.M., M.I.L. and G.P.A. are members of COST Action CA17112.

Author information

Introduction (R.J.A.); Epidemiology (N.C., E.S.B. and H.D.); Mechanisms/pathophysiology (N.K., G.A.K.-U. and A.S.); Diagnosis, screening and prevention (R.J.A., G.P.A., H.D., M.I.L., P.B.W. and M.M.); Prognosis (E.S.B.); Management (N.C.); Quality of life (A.S. and M.I.L.); Outlook (N.K., G.P.A. and R.J.A.); Overview of Primer (R.J.A. and M.I.L.).

Correspondence to Raul J. Andrade or M. Isabel Lucena.

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Nature Reviews Disease Primers thanks M. Chen, H. Jaeschke, J. Lewis, T. Yokoi, and other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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