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

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.