Impact of cystic fibrosis transmembrane conductance regulator modulator therapies on liver stiffness and liver enzymes: An observational perspective single‐center cohort study

Abstract Objectives The efficacy of cystic fibrosis transmembrane conductance regulator ( CFTR )‐modulator therapies in preventing or ameliorating cystic fibrosis liver disease (CFLD) by correcting CFTR in cholangiocytes is not well‐documented. This study aimed to assess liver function during CFTR‐modulators. Methods Patients eligible to start Elexacaftor/Tezacaftor/Ivacaftor (July 2021–December 2022), followed‐up at the Piedmont Cystic Fibrosis reference Centre of the Città della Salute e della Scienza, Turin , Italy , were enrolled through a prospective single‐center cohort study and evaluated using hematological exams and liver stiffness measurement (LSM) before treatment and at 1, 3, 6, and 12 months thereafter. The treated group was compared to a group of untreated people with cystic fibrosis (pwCF), evaluated at baseline and after 12 months. Results Sixty‐nine treated pwCF, mean age 16.0 years, 51% males, were compared to 130 non‐treated pwCF, mean age 12.14 years, 49% males. Treated pwCF were classified by LSM as normal (<5 kPa) ( N = 44, 64%), mild liver fibrosis (5–7 kPa) ( N = 16, 23%), or moderate‐severe fibrosis (>7 kPa) ( N = 9, 13%). A significant trend in LSM reduction was observed at Month 12 in the subgroups with LSM 5–7 kPa and LSM > 7 kPa (−1.05, p = 0.016 and −1.57, p = 0.022, respectively). PwCF without fibrosis at baseline and non‐treated pwCF showed no LSM change over time. Liver enzyme levels increased at Month 12, trend mirrored in non‐treated pwCF for AST level, remaining within normal ranges. Conclusions During treatment, a significant LSM reduction was observed in pwCF with liver fibrosis at baseline, especially after Month 1. This rapid improvement could be multifactorial and may suggest a potential early response without significant liver toxicity.