ArticleClinical pharmacology and therapeutics2026
Quantitative Systems Toxicology Predicts Ivacaftor-Induced Oxidative Stress Contributes to CFTR Modulator Hepatotoxicity.
Article in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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
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Who cites it
4 citing papers in PubMed.
- A descriptive case series of hepatotoxicity associated with CFTR modulators and possible relevance of pharmacogenetic polymorphisms in cystic fibrosis patients.British journal of clinical pharmacology · 2026Article
- Prenatal CFTR modulator therapy for fetal cystic fibrosis: Emerging evidence, clinical considerations, and future directions.Pregnancy (Hoboken, N.J.) · 2026Review
- Decoding liver injury in cystic fibrosis: How to tell drug-induced liver injury from cystic fibrosis liver disease.World journal of gastroenterology · 2026Review
- Evaluation of Elexacaftor/Tezacaftor/Ivacaftor-Mediated Drug-Induced Liver Injury Using a Liver-On-Chip Model.Clinical and translational science · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Cystic fibrosis (CF) is a chronic hereditary disease that affects tens of thousands of people worldwide. The introduction of CFTR modulator therapies such as elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved the quality of life of people with CF. However, ETI has been shown in clinical trials to cause elevations in liver enzymes, and real-world cases of drug-induced liver injury (DILI) have also been reported. The mechanism of ETI-mediated DILI is currently unknown, hindering the development of more effective mitigation strategies for this adverse reaction. Through in vitro assays and quantitative systems toxicology modeling using DILIsym, this study revealed that ivacaftor contributed most significantly to ETI-mediated DILI, primarily via reactive oxygen species production, resulting in mitochondrial dysfunction due to electron transport chain inhibition. DILIsym modeling also predicted liver enzyme elevations following daily dosing of ETI at a comparable frequency (6.0%) to that of clinical data (8.0%). Simulations of the therapeutic effects of DILI mitigation strategies for ETI showed that dose reduction and antioxidant administration may significantly reduce the frequency of liver enzyme elevations due to ETI.
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Registered trials
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