ReviewInternational journal of molecular sciences2021
Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hepatotoxicity of ICI monotherapy or combination therapy in HCC: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Genetic Variants at the NAT2 and HLA-DOA are Associated With Anti-Tuberculosis Drug-Induced Liver Injury Susceptibility and Clinical Manifestations in Western Chinese Populations.Immunity, inflammation and disease · 2026Article
- Application of metabolomics in drug-induced liver injury: A systematic review.Journal of translational internal medicine · 2026Article
- Tirzepatide-Associated Severe Hepatocellular Injury: A Case Report and Diagnostic Considerations.Diagnostics (Basel, Switzerland) · 2026Article
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Drug-Induced Liver Injury From a Novel Antifungal - Olorofim.ACG case reports journal · 2026Article
- Article
- Hepatotoxicity Risk of Isoniazid in Patients with Autoimmune Rheumatic Diseases and Prior Liver Injury Due to Disease-Modifying Antirheumatic Drugs: A Single-Center Experience and Literature Review.Journal of clinical medicine · 2026Article
- RUCAM-ascertained immunology and autoimmunity specifics of six idiosyncratic drug-induced liver injury types with refined classification: their individual complex molecular interplay.Frontiers in immunology · 2026Review
- A pharmacist-led framework for antibiotic-associated liver injury: from pharmacovigilance signals to bedside surveillance with the updated RUCAM and susceptibility markers.Frontiers in pharmacology · 2026Review
- A review on adverse drug reaction related to medication in health sector: an account of what we have discovered and implemented-pharmacovigilance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Khat-associated Autoimmune Hepatitis: A Review with RUCAM Analysis.Journal of clinical and translational hepatology · 2025Review
- TAK-994 mechanistic investigation into drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Drug-Induced Liver Injury Secondary to Endocrine Therapy With Aromatase Inhibitors: A Case Report.Cureus · 2025Article
- Drug-Induced Liver Injury-Pharmacological Spectrum Among Children.International journal of molecular sciences · 2025Review
- Genetic and Genomic Approaches to the Study of Drug-Induced Liver Injury.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Ferroptosis and Intrinsic Drug-induced Liver Injury by Acetaminophen and Other Drugs: A Critical Evaluation and Historical Perspective.Journal of clinical and translational hepatology · 2024Review
- Uncovering the mechanism of troglitazone-mediated idiosyncratic drug-induced liver injury with individual-centric models.Archives of toxicology · 2024Article
- Review
- The use of PD-1 functional knockout rats to study idiosyncratic adverse reactions to nevirapine.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.