Drug induced liver injury: an update

Garcia-Cortes, Miren; Robles-Diaz, Mercedes; Stephens, Camilla; Ortega-Alonso, Aida; Lucena, M. Isabel; Andrade, Raúl J.

doi:10.1007/s00204-020-02885-1

Review Article
Published: 27 August 2020

Drug induced liver injury: an update

Miren Garcia-Cortes^1,2^na1,
Mercedes Robles-Diaz^1,2^na1,
Camilla Stephens^1,2,
Aida Ortega-Alonso^1,2,
M. Isabel Lucena ORCID: orcid.org/0000-0001-9586-4896^1,2^na2 &
Raúl J. Andrade^1,2^na2

Archives of Toxicology volume 94, pages 3381–3407 (2020)Cite this article

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Abstract

Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors.

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Funding

The present study has been supported by grants of the Instituto de Salud Carlos III co-founded by Fondo Europeo de Desarrollo Regional-FEDER (contract numbers: PT17/0017/0020, PI 18-01804, PI 18-00901, UMA-18 FEDERJA-193), the Consejería de Salud de la Junta de Andalucía (PI-0274/2016, PI-0285/2016) and by the Agencia Española del Medicamento. MRD holds an Acción B de refuerzo investigador research contract from the Servicio Andaluz de Salud (Expediente B-0002–2019). CIBERehd is funded by Instituto de Salud Carlos III. We acknowledge the support from European Cooperation in Science & Technology (COST) Action CA17112 Prospective European Drug-Induced Liver Injury Network. MGC, CS, AOA, MIL, MRD and RJA, are member of COST Action CA17112.

Author information

Miren Garcia-Cortes and Mercedes Robles-Diaz share first authorship.
M. Isabel Lucena and Raúl J. Andrade share senior authorship.

Affiliations

Unidad de Gestión Clínica de Aparato Digestivo y Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
Miren Garcia-Cortes, Mercedes Robles-Diaz, Camilla Stephens, Aida Ortega-Alonso, M. Isabel Lucena & Raúl J. Andrade
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
Miren Garcia-Cortes, Mercedes Robles-Diaz, Camilla Stephens, Aida Ortega-Alonso, M. Isabel Lucena & Raúl J. Andrade

Authors

Miren Garcia-Cortes
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Mercedes Robles-Diaz
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Camilla Stephens
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Aida Ortega-Alonso
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M. Isabel Lucena
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Raúl J. Andrade
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Correspondence to Raúl J. Andrade.

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Garcia-Cortes, M., Robles-Diaz, M., Stephens, C. et al. Drug induced liver injury: an update. Arch Toxicol 94, 3381–3407 (2020). https://doi.org/10.1007/s00204-020-02885-1

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Received: 21 July 2020
Accepted: 17 August 2020
Published: 27 August 2020
Issue Date: October 2020
DOI: https://doi.org/10.1007/s00204-020-02885-1

Keywords

Drug-induced liver injury
Hepatotoxicity
Risk factors
Causality assessment
Biomarkers
Management