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

摘要

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?