ArticleThe Journal of pharmacology and experimental therapeutics2010
Intrinsic versus idiosyncratic drug-induced hepatotoxicity--two villains or one?
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 152 citations in OpenAlex.
- Spontaneous Fluctuations in Liver Biochemistries in Patients with Compensated NASH Cirrhosis: Implications for Drug Hepatotoxicity Monitoring.Drug safety · 2020Trial
- In vitro approaches for modelling gut-liver crosstalk in drug-induced liver injury.Archives of toxicology · 2026Review
- A Multimodal deep learning method for predicting drug-induced liver injury using structural and sequential molecular representations.Journal of computer-aided molecular design · 2026Article
- AI-enhanced clinical trial-in-a-dish platform for improved DILI risk classification and mechanistic insights into hepatotoxicity.Frontiers in toxicology · 2026Article
- Costs, Demographics, and Causative Agents in Patients Hospitalized for Drug Induced Liver Injury: Trends in a Large Academic Healthcare System.Clinical and experimental gastroenterology · 2026Article
- A newFrontiers in toxicology · 2026Article
- Review
- Khat-associated Autoimmune Hepatitis: A Review with RUCAM Analysis.Journal of clinical and translational hepatology · 2025Review
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Clinical features and prognosis of drug-induced liver injury in patients with non-alcoholic fatty liver.World journal of hepatology · 2025Article
- Drug-Induced Liver Injury-Pharmacological Spectrum Among Children.International journal of molecular sciences · 2025Review
- HIVIL: A humanNAM journal · 2025Article
- The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats.BMC complementary medicine and therapies · 2024Article
- An original donor-dependent spheroid system for the prediction of idiosyncratic drug-induced liver injury risk.In vitro models · 2023Article
- Immune-mediated herb-induced liver injury: a potential association with herbal artemisinin use as supported by the updated RUCAM.BMJ case reports · 2023Article
- Diclofenac Disrupts the Circadian Clock and through Complex Cross-Talks Aggravates Immune-Mediated Liver Injury-A Repeated Dose Study in Minipigs for 28 Days.International journal of molecular sciences · 2023Article
- Amlodipine-Induced Liver Injury.Cureus · 2022Article
- Article
- Is There an Increased Risk of Hepatotoxicity with Metamizole? A Comparative Cohort Study in Incident Users.Drug safety · 2021Article
- Drug-induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies.Journal of biochemical and molecular toxicology · 2021Review
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 1 institution in 1 country.
Funding
Abstract
"Intrinsic" and "idiosyncratic" drug-induced liver injury reactions are commonly thought to arise by different modes of action. Intrinsic toxicity is reproducible in animals and occurs dose-dependently at sublethal doses. Environmental and genetic sensitivity factors can influence the toxicity of intrinsic hepatotoxicants. Among these is inflammatory stress. For example, exposure of mice to inflammatory bacterial lipopolysaccharide (LPS) causes a leftward shift in the dose-response relationship for acetaminophen hepatotoxicity; that is, acetaminophen toxicity is enhanced by LPS-induced inflammatory stress. Idiosyncratic reactions present themselves very differently than intrinsic ones; they happen in a minority of patients, with variable time of onset and no obvious relationship to drug dose, and they are not reproducible in usual animal tests. Although these characteristics seem to distinguish them from intrinsic reactions, consideration of fundamental principles of dose response can explain the differences. For a drug that causes idiosyncratic hepatotoxicity, the liver may not be a typical target for toxicity because the dose-response curve for hepatotoxicity lies to the right of the lethal dose. However, a sporadically occurring sensitivity factor, such as an inflammatory episode, could shift the dose-response curve for hepatotoxicity to the left, thereby bringing hepatotoxic doses into the therapeutic range. This hypothesis can account for the bizarre characteristics of idiosyncratic reactions and is supported by recent results showing that several drugs associated with human idiosyncratic reactions can be rendered hepatotoxic to rodents upon interaction with an inflammatory stimulus. In light of this view, intrinsic and idiosyncratic reactions may not be that different after all.
Indexed as
Identifiers
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.