Quantitative Systems Toxicology Predicts Ivacaftor-Induced Oxidative Stress Contributes to CFTR Modulator Hepatotoxicity.

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

SUBMITTER: Shi A 

PROVIDER: S-EPMC12746516 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature