ReviewAnnals of translational medicine2021
Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues.
Review in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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
30 citing papers in PubMed, 55 citations in OpenAlex.
- A multiparametric in vitro strategy for small molecule drug-induced liver injury risk mitigation in early drug development.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Toxicological evaluation of Lagerstroemia speciosa (L.) Martyn and Lagerstroemia tomentosa C.Presl extracts using a liver organ-on-a-chip system.Scientific reports · 2026Article
- An Exploratory Study on the Pathogenic Role of Faecal Extracellular Vesicles in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression and in Drug-Induced Liver Injury.Journal of extracellular vesicles · 2026Article
- [Differences in the mechanisms, diagnostic biomarkers, and therapeutic strategies of drug-induced liver injury caused by traditional Chinese and Western medicines].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- 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
- Drug-Induced Autoimmune Hepatitis by Varenicline and Infliximab as a Continuous Disease Spectrum with Two Different Flares: Acute Liver Injury Followed by Hepatic Autoimmunity.International journal of molecular sciences · 2025Review
- Ornidazole-Induced Liver Injury: The Clinical Characterization of a Rare Adverse Reaction and Its Implications from a Multicenter Study.Biomedicines · 2025Article
- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- Direct Effects of Clinically Relevant Antibiotics on Mitochondrial Respiration.International journal of molecular sciences · 2025Article
- Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Review
- Copper, Iron, Cadmium, and Arsenic, All Generated in the Universe: Elucidating Their Environmental Impact Risk on Human Health Including Clinical Liver Injury.International journal of molecular sciences · 2024Review
- Human Leucocyte Antigen Genetics in Idiosyncratic Drug-Induced Liver Injury with Evidence Based on the Roussel Uclaf Causality Assessment Method.Medicines (Basel, Switzerland) · 2024Review
- Exploring Individual Variability in Drug-Induced Liver Injury (DILI) Responses through Metabolomic Analysis.International journal of molecular sciences · 2024Article
- First-in-human phase 1 trial evaluating safety, pharmacokinetics, and pharmacodynamics of NLRP3 inflammasome inhibitor, GDC-2394, in healthy volunteers.Clinical and translational science · 2023Article
- Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM.International journal of molecular sciences · 2023Observational
- Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use.International journal of molecular sciences · 2023Review
- Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations.International journal of molecular sciences · 2023Review
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical features of idiosyncratic drug induced liver injury (DILI) are well described in cases that have been assessed for causality using the Roussel Uclaf Causality Assessment Method (RUCAM), but our understanding of the mechanistic steps leading to injury is fragmentary. The difficulties describing mechanistic events can be traced back to the lack of an animal model of experimental idiosyncratic DILI that can mimic the genetic requirements of human idiosyncratic DILI. However, immune tolerance plays a dominant role in the immune response of the liver, and impairment of immune tolerance with immune checkpoint inhibitors increases DILI in both humans and animals. This may provide one method to study the individual steps involved. In general. the human DILI liver is a secret keeper providing little insight into what occurs in the diseased organ. Sufficient evidence exists that most idiosyncratic cases are mediated by the adaptive immune system, which depends on stimulation of the innate immune system, but the triggering factors are unknown. It is attractive to hypothesize that the gut microbiome plays a role; however, it is very difficult to study. Similarly, exosomes are likely to play an important role in communication between hepatic cells and the immune system, but there is a lack of data on blood exosomes in affected patients. Reactive metabolites are likely to play an important role. This is supported by the current analysis, which revealed an association between metabolism by cytochrome P450 and drugs most commonly involved in causing idiosyncratic DILI with causality verified by RUCAM. Circumstantial evidence suggests that reactive oxygen species (ROS) generated by cytochrome P450 could be responsible for the initial steps of injury, but details are unknown. In conclusion, most of the mechanistic steps leading to idiosyncratic DILI remain unclear.
Indexed as
Identifiers
What Socratic 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 Socratic graph.