Improvement of Cystic Fibrosis-Associated Liver Disease in Adults on Long-Term Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have been reported to improve lung function and reduce CF exacerbations. We aimed to investigate the efficacy of CFTR-modulators in CF-associated liver disease (CFLD) during long-term treatment. Longitudinal data were collected from genetically confirmed adult CF patients receiving CFTR-modulators. CFLD was diagnosed using conventional criteria combined with liver stiffness measurement (LSM). A total of 57 patients [56.1% male; median age at baseline (T0), 26 years (interquartile range [IQR], 23-35)] were included. Patients received lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor for a median of 43 months (range, 15-123) until last assessment (T2). The prevalence of CFLD decreased from 15 (26.3%) at T0 to 8 (14.0%) at T2 (<i>p</i> = 0.016), and no new cases of CFLD were observed. Median LSM decreased from 6.2 (IQR 4.9-8.0) to 5.0 kPa (IQR 4.1-6.2) in the overall cohort (<i>p</i> < 0.001) and from 10.2 (IQR 6.8-13) to 6.2 kPa (IQR 5.0-12.4) in the CFLD subgroup (<i>p</i> = 0.025). Mild, transient fluctuations in liver enzymes occurred in 26.3% of patients. In conclusion, adults with CF receiving long-term CFTR modulators, showed improvement of liver disease assessed by ultrasonography and transient elastography. At the last assessment, half of the patients no longer met the criteria for CFLD.