Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis

• Published in: Journal of cystic fibrosis Vol. 24; no. 3; pp. 574 - 580
• Main Authors: Terlizzi, Vito, Fevola, Cristina, Cecchetti, Martina, Terminiello, Alberto, Curci, Franco, Bartolini, Elisa, Rubino, Chiara, Stinco, Mariangela, Carrera, Simona, Bonomi, Paolo, Taccetti, Giovanni, Sellers, Zachary M., Indolfi, Giuseppe
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2025
• Subjects: Aminophenols - administration & dosage; Aminophenols - therapeutic use; Benzodioxoles - administration & dosage; Benzodioxoles - therapeutic use; CAP; CFHBI; CFLD; CFTR modulator; Child; Chloride Channel Agonists - administration & dosage; Chloride Channel Agonists - therapeutic use; Cystic Fibrosis - blood; Cystic Fibrosis - complications; Cystic Fibrosis - diagnosis; Cystic Fibrosis - drug therapy; Drug Combinations; Elasticity Imaging Techniques - methods; Female; Hematologic Tests - methods; HEMT; Humans; Indoles - administration & dosage; Indoles - therapeutic use; Liver - diagnostic imaging; Liver Cirrhosis - blood; Liver Cirrhosis - diagnosis; Liver Cirrhosis - etiology; Liver Function Tests - methods; Male; Pediatrics; Phenylpropionates - administration & dosage; Phenylpropionates - therapeutic use; Prospective Studies; Pulmonary/Respiratory; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Pyrrolidines - therapeutic use; Quinolines; Quinolones - administration & dosage; Quinolones - therapeutic use; Stiffness; Treatment Outcome; Pediatrics; CAP; CFTR modulator; CFLD; HEMT; Stiffness; CFHBI
• ISSN: 1569-1993; 1873-5010; 1873-5010
• DOI: 10.1016/j.jcf.2024.12.010

•In children with CF and liver involvement, ETI significantly reduced liver stiffness.•ETI normalized ALT e GGT in children with CF and pre-existing abnormalities.•ETI normalized liver fibrosis indices in CF children with pre-existing abnormalities.•A significant reduction in platelets was observed in children on ETI.•A good hepatobiliary safety profile of ETI was observed. Elexacaftor-tezacaftor–ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6–12 years started on ETI therapy. Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines. 27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range. ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.