The cystic fibrosis transmembrane conductance regulator (CFTR) 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 cystic fibrosis (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 (GGT), AST-to-Platelet Index (APRI), and GGT-to-Platelet Ratio (GPR) 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.

ZMS is a paid consultant for Vertex Pharmaceuticals, but has no financial interest in the company. Vertex had no involvement in any aspect of the research (including funding, study design, or access to the data).

Funding provided by the Cystic Fibrosis Foundation (SELLER16L0, SELLER19GE0, SELLER20A0-KB to Z.M.S), National Institute of Diabetes and Digestive and Kidney Diseases (K08DK124684 to Z.M.S.), and Stanford University (Z.M.S). Funding sources were not involved in the study design.

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