ReviewInternational journal of molecular sciences2021
Idiosyncratic Drug Induced Liver Injury, Cytochrome P450, Metabolic Risk Factors and Lipophilicity: Highlights and Controversies.
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 24 papers.
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Who cites it
24 citing papers in PubMed.
- Trial
- Role of the Gut-Liver-Kidney Axis in Disease Manifestation and Biomarker Alterations.International journal of molecular sciences · 2026Review
- Machine Learning-Based Models to Predict Drug-Induced Liver Injury (DILI) to Assist Medicinal Chemistry.Journal of medicinal chemistry · 2026Review
- [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
- Impact of halogenation on scaffold toxicity assessed using HD-GEM machine learning model.Briefings in bioinformatics · 2025Article
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Identification of liver proteins as biomarker for postmortem diagnosis of heat stroke through proteomics.Scientific reports · 2025Article
- 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
- Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM.Journal of clinical and translational hepatology · 2023Review
- 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
- Drug-induced liver injury: a comprehensive review.Therapeutic advances in gastroenterology · 2023Review
- Treatment of Drug-Induced Liver Injury.Biomedicines · 2022Review
- Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.Molecules (Basel, Switzerland) · 2022Article
- Liver Injury with Nintedanib: A Pharmacovigilance-Pharmacokinetic Appraisal.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Study on the Characteristics of Small-Molecule Kinase Inhibitors-Related Drug-Induced Liver Injury.Frontiers in pharmacology · 2022Article
- Review
Corrections and comments
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Authors and funding
2 authors.
Funding
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Abstract
Progress in understanding the mechanisms of the idiosyncratic drug induced liver injury (iDILI) was highlighted in a scientometric investigation on the knowledge mapping of iDILI throughout the world, but uncertainty remained on metabolic risk factors of iDILI, the focus of the present review article. For the first time, a quantitative analysis of 3312 cases of iDILI assessed for causality with RUCAM (Roussel Uclaf Causality Assessment Method) showed that most drugs (61.1%) were metabolized by cytochrome P450 (CYP) isoforms: 49.6% by CYP 3A4/5, 24.6% by CYP 2C9, 13.2% by CYP 2E1, 7.3% by CYP 2C19, 3.5% by CYP 1A2 and 1.8% by CYP 2D6. Other studies showed high OR (odds ratio) for drugs metabolized by unspecified CYPs but the iDILI cases were not assessed for causality with RUCAM, a major shortcoming. In addition to critical comments on methodological flaws, several risk factors of iDILI were identified such as high but yet recommended daily drug doses, actual daily drug doses taken by the patients, hepatic drug metabolism and drug lipophilicity. These risk factors are subject to controversies by many experts seen critically also by others who outlined that none of these medication characteristics is able to predict iDILI with high confidence, leading to the statement of an outstanding caveat. It was also argued that all previous studies lacked comprehensive data because the number of examined drugs was relatively small as compared to the number of approved new molecular entities or currently used oral prescription drugs. In conclusion, trends are evident that some metabolic parameters are likely risk factors of iDILI but strong evidence can only be achieved when methodological issues will be successfully met.
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