Published online Feb 27, 2022. doi: 10.4254/wjh.v14.i2.411
Peer-review started: October 21, 2021
First decision: December 2, 2021
Revised: December 15, 2021
Accepted: February 16, 2022
Article in press: February 16, 2022
Published online: February 27, 2022
Processing time: 123 Days and 18.5 Hours
Due to improvements in pulmonary care in cystic fibrosis (CF), CF-related liver disease (CFRLD) is emerging as a leading cause of morbidity and mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators correct the CFTR dysfunction and dramatically improve pulmonary outcomes, but the effects of CFTR modulators on CFRLD have not been evaluated.
Currently, there is insufficient data examining the impact of CFTR modulators on the incidence of cirrhosis among patients with CF.
To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.
A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis.
A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodeoxycholic acid, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (P = 0.05), patients on Ursodiol (P < 0.001), and patients on dual therapy (P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (P < 0.001) or patients on Ursodiol and CFTR modulators (P = 0.01).
Patients treated with CFTR modulators have a lower incidence of cirrhosis compared to no treatment, ursodiol, or combination therapy.
The risk of developing cirrhosis is lower among patients treated with CFTR modulators than those not treated with CFTR modulators. Whether this represents a selection bias or represents a treatment effect of CFTR modulators should be studied in a prospective, randomized study.