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Drug-induced liver injury
Open accessAbstract
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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“The vast majority of cases of DILI occur at therapeutic doses in a small proportion of individuals exposed to the drug, representing an idiosyncratic reaction, and therefore unpredictable based on the drug's mechanism of action and related to the uniqueness of the individual [1,2].”
From DILI Differences and Similarities between the US and Europe (2026) · cites this paper as [1]
In the citing paper
“Drug-induced liver injury (DILI) is an uncommon adverse reaction to drugs, and other chemicals, including herbal and dietary supplements (HDS).”
From DILI Differences and Similarities between the US and Europe (2026) · cites this paper as [1]
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Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
Cited work 10.1128/aac.04976-14 · retracted 2015-12-28 · notice 10.1128/aac.04976-14 · this paper published 2019-08-22
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“Francis, B. et al. Temporary removal: reference intervals for putative biomarkers of drug-induced liver injury and liver regeneration in healthy human volunteers. J. Hepatol. https://doi.org/10.1016/j.jhep.2018.04.024 (2018).”
Cited work 10.1016/j.jhep.2018.04.024 · retracted 2018-05-03 · notice 10.1016/j.jhep.2018.04.024 · this paper published 2019-08-22
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Metadata
- Authors
- Andrade, R. J., Chalasani, N., Björnsson, E. S., Suzuki, A., Kullak-Ublick, G. A., Watkins, P. B., Devarbhavi, H., Merz, M., Lucena, M. I., Kaplowitz, N., & Aithal, G. P.
- Affiliations
- Indiana University School of Medicine (US)
- Duke University (US)
- Novartis (Switzerland) (CH)
- University of North Carolina at Chapel Hill (US)
- St.John's Medical College Hospital (IN)
- University of Zurich (CH)
- Spanish Clinical Research Network (ES)
- Nottingham University Hospitals NHS Trust (GB)
- Corresponding author
- Lucena, M. Isabel
- ORCID
- Venue
- Nature Reviews Disease Primers
- Published
- 2019-08-22
- Volume
- 5
- Issue
- 1
- Pages
- 58-58
- ISSN
- 2056-676X (ISSN-L)
- OpenAlex
- W1565605888
- Cited by
- 924
- References
- 982
- Citations by year
- 2026: 152 · 2025: 197 · 2024: 161 · 2023: 127 · 2022: 145 · 2021: 97 · 2020: 38
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- Nature Reviews Disease Primers (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Pharmacology (medical) › Drug-Induced Adverse Reactions
- Keywords
- drug-induced liver injury, idiosyncratic drug reactions, xenobiotic toxicity, genetic susceptibility, hepatic metabolism, immune response, corticosteroids, immune checkpoint inhibitors, hepatotoxicity
- MeSH terms
- Biopsy, Humans, Risk Factors, Biomarkers, Chemical and Drug Induced Liver Injury
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