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Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis

The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which...

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Autores principales: Levitte, Steven, Fuchs, Yonathan, Wise, Russell, Sellers, Zachary M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019140/
https://www.ncbi.nlm.nih.gov/pubmed/36662672
http://dx.doi.org/10.1097/HC9.0000000000000010
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author Levitte, Steven
Fuchs, Yonathan
Wise, Russell
Sellers, Zachary M.
author_facet Levitte, Steven
Fuchs, Yonathan
Wise, Russell
Sellers, Zachary M.
author_sort Levitte, Steven
collection PubMed
description The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.
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spelling pubmed-100191402023-03-16 Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis Levitte, Steven Fuchs, Yonathan Wise, Russell Sellers, Zachary M. Hepatol Commun Original Articles The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease. Lippincott Williams & Wilkins 2023-01-20 /pmc/articles/PMC10019140/ /pubmed/36662672 http://dx.doi.org/10.1097/HC9.0000000000000010 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/) (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Original Articles
Levitte, Steven
Fuchs, Yonathan
Wise, Russell
Sellers, Zachary M.
Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title_full Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title_fullStr Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title_full_unstemmed Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title_short Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
title_sort effects of cftr modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019140/
https://www.ncbi.nlm.nih.gov/pubmed/36662672
http://dx.doi.org/10.1097/HC9.0000000000000010
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