{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:44:57Z","timestamp":1763981097894,"version":"3.45.0"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ETI), a cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, has provided great improvements in lung function and well\u2010being for people with CF. The use of ETI has been complicated by reports of rare but significant liver function test elevations in clinical trials and drug\u2010induced liver injury (DILI) in real\u2010world use. Previous research by our group revealed that oxidative stress is the major driver of ETI\u2010mediated DILI, and in silico ETI DILI simulations resulted in elevations of the emerging biomarker glutamine dehydrogenase (GLDH) which match the time course of predicted transaminase elevations. The assessment of emerging biomarkers and therapeutic strategies in a clinically relevant model will spur the development of more effective treatments for ETI\u2010mediated DILI. This study used the human\u2010relevant liver\u2010on\u2010chip model to investigate GLDH as a biomarker and ETI dose reduction and silymarin antioxidant administration as therapeutic strategies for ETI\u2010mediated DILI. We found that GLDH was not as sensitive as ALT and albumin for detecting DILI due to ETI. Dose reduction was a more effective treatment strategy for ETI DILI than silymarin, which did not significantly lower ALT levels.<\/jats:p>","DOI":"10.1111\/cts.70400","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:27:18Z","timestamp":1762957638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Elexacaftor\/Tezacaftor\/Ivacaftor\u2010Mediated Drug\u2010Induced Liver Injury Using a Liver\u2010On\u2010Chip Model"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6939-039X","authenticated-orcid":false,"given":"Alan","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6565-6779","authenticated-orcid":false,"given":"Palak","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-3506","authenticated-orcid":false,"given":"Zhang\u2010Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Research Lab Core, Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-3310","authenticated-orcid":false,"given":"Paul M.","family":"Beringer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California  Los Angeles California USA"},{"name":"USC Anton Yelchin CF Clinic  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.8120"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.01.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00454-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.07.001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.14309\/01.ajg.0000784684.45906.5d"},{"key":"e_1_2_10_8_1","article-title":"Acute Liver Failure in a Patient with Cystic Fibrosis Taking Triple Combination Modulator. 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