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CASE REPORT article

Front. Pediatr.
Sec. Pediatric Gastroenterology, Hepatology and Nutrition
Volume 12 - 2024 | doi: 10.3389/fped.2024.1457517
This article is part of the Research Topic Gastrointestinal and Hepatic Involvement in Cystic Fibrosis in the era of CFTR Modulator Therapies View all 3 articles

Case Report: A Delicate Equilibrium of Exocrine Pancreatic Recovery and Hepatotoxicity with Elexacaftor/Tezacaftor/Ivacaftor Therapy in a Pediatric Patient with Cystic Fibrosis

Provisionally accepted
Michael P. Coughlin Michael P. Coughlin 1*Senthilkumar Sankararaman Senthilkumar Sankararaman 2,3Erica A. Roesch Erica A. Roesch 1,3Emily D. Certo Emily D. Certo 4Benjamin L. Brej Benjamin L. Brej 5Michael W. Konstan Michael W. Konstan 1,3
  • 1 Division of Pediatric Pulmonology. Rainbow Babies & Children's Hospital, Cleveland, United States
  • 2 Division of Pediatric Gastroenterology, Rainbow Babies & Children's Hospital, Cleveland, United States
  • 3 Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, United States
  • 4 Department of Pediatrics, Rainbow Babies & Children's Hospital, Cleveland, United States
  • 5 College of Medicine, The Ohio State University, Columbus, Ohio, United States

The final, formatted version of the article will be published soon.

    This case report presents a comprehensive evaluation of the complex balance of therapeutic benefits and potential risks associated with the cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) therapy in managing an eight-year-old male with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). While ETI therapy significantly enhanced exocrine pancreatic function, it led to hepatotoxicity, necessitating therapy discontinuation. Attempts to restart ETI at reduced doses were unsuccessful due to persistent hepatic dysfunction. Reduced ETI dosing frequency, implemented due to hepatic dysfunctions, did not result in substantial therapeutic benefits. Clinical markers showed a resurgence of severe EPI and sustained need for gastrostomy tube feeds, with only modest improvement in hepatic function compared to the period following ETI cessation or during prior use of CFTR modulator therapy with lumacaftor/ivacaftor. This case underscores the importance of personalized therapeutic approaches, biomarker-guided monitoring, and multidisciplinary insights to optimize CF management while also highlighting the ongoing need for research to mitigate hepatotoxicity risks and ensure long-term therapeutic efficacy.

    Keywords: case report, cystic fibrosis (CF), cystic fibrosis transmembrane conductance regulator (CFTR) modulators, elexacaftor/tezacaftor/ivacaftor (ETI), exocrine pancreatic function, Hepatotoxicity

    Received: 30 Jun 2024; Accepted: 16 Sep 2024.

    Copyright: © 2024 Coughlin, Sankararaman, Roesch, Certo, Brej and Konstan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Michael P. Coughlin, Division of Pediatric Pulmonology. Rainbow Babies & Children's Hospital, Cleveland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.