Increase of liver stiffness and altered bile acid metabolism after triple CFTR modulator initiation in children and young adults with cystic fibrosis

Schnell A, Jüngert JM, Klett D, Hober H, Kaiser N, Ruppel R, Geppert A, Tremel C, Sobel J, Plattner E, Schmitt-Grohe S, Zirlik S, Strobel D, Neurath M, Knieling F, Rauh M, Wölfle J, Hörning A, Regensburger A (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Liver International Wiley-Blackwell

DOI: 10.1111/liv.15544

Abstract

Background: Novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (elexacaftor/tezacaftor/ivacaftor—ETI) promise clinically significant and sustained improvements for patients with cystic fibrosis (CF). In this study, we investigated the impact of ETI therapy on liver stiffness and bile acid metabolism in a cohort of children and young adults with CF. Methods: A prospective observational study (NCT05576324) was conducted from September 2020 to November 2021 enrolling CF patients naive to ETI. Standard laboratory chemistry, sweat test, lung function, share wave velocity (SWV) derived by acoustic radiation force impulse imaging (ARFI) and serum bile acid profiles were assessed before and 6 months after induction of ETI therapy. Results: A total of 20 patients (10 aged <20 years) completed the study. While lung function and BMI improved after ETI therapy, ARFI SWV increased in CF patients <20 years of age (from 1.27 to 1.43 m/s, p = 0.023). Bile acid (BA) profiles revealed a decrease in unconjugated (5.75 vs 1.46, p = 0.007) and increase in glycine-conjugated derivatives (GCDCA) (4.79 vs 6.64 p = 0.016). There was a positive correlation between ARFI SWV values and GCDCA (r = 0.80, p < 0.0001). Glycine-conjugated BA provided high diagnostic accuracy to predict increased ARFI measurements (AUC 0.90) and clinical (Colombo) CFLD grading (AUC 0.97). Conclusions: ARFI SWV and bile acid profiles provide evidence for early increase in liver stiffness and altered bile acid metabolism in young CF patients after initiation of ETI and may serve as synergistic measures for detection of hepatic complications during ETI therapy.

Authors with CRIS profile

Alexander Schnell Department of Paediatrics and Adolescent Medicine Daniel Klett Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Hannah Hober Medizinische Fakultät Christina Tremel Department of Paediatrics and Adolescent Medicine Sabine Zirlik Medizinische Fakultät Deike Strobel Medizinische Fakultät Markus Neurath Lehrstuhl für Innere Medizin I Ferdinand Knieling Department of Paediatrics and Adolescent Medicine Manfred Rauh Department of Paediatrics and Adolescent Medicine Joachim Wölfle Lehrstuhl für Kinder- und Jugendmedizin André Hörning Department of Paediatrics and Adolescent Medicine Adrian Regensburger Department of Paediatrics and Adolescent Medicine

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

J089: Multispectral optoacoustic tomography for non invasive characterization of strictures in Crohn’s disease Jan. 1, 2021 - March 31, 2024

How to cite

APA:

Schnell, A., Jüngert, J.M., Klett, D., Hober, H., Kaiser, N., Ruppel, R.,... Regensburger, A. (2023). Increase of liver stiffness and altered bile acid metabolism after triple CFTR modulator initiation in children and young adults with cystic fibrosis. Liver International. https://doi.org/10.1111/liv.15544

MLA:

Schnell, Alexander, et al. "Increase of liver stiffness and altered bile acid metabolism after triple CFTR modulator initiation in children and young adults with cystic fibrosis." Liver International (2023).

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