Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis
Mitchell L Ramsey, Michael R Wellner, Kyle Porter, Stephen E Kirkby, Susan S Li, Luis F Lara, Sean G Kelly, A James Hanje, Lindsay A Sobotka
Mitchell L Ramsey, Sean G Kelly, A James Hanje, Lindsay A Sobotka, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
Michael R Wellner, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, Columbus, OH 43210, United States
Kyle Porter, Department of Biostatistics, The Ohio State University, Columbus, OH 43210, United States
Stephen E Kirkby, Department of Pulmonary and Critical Care Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
Susan S Li, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
Luis F Lara, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Columbus, OH 43210, United States
Author contributions: Ramsey ML and Sobotka LA designed the research project, drafted the manuscript, and provided final approval of the manuscript; Porter K performed the statistical analysis and provided final approval of the manuscript; Wellner MR, Kirkby S, Li SS, Lara LF, Kelly SG, and Hanje AJ made critical revisions related to important intellectual content of the manuscript and provided final approval of the manuscript.
Institutional review board statement: The Ohio State University Institution Review Board deemed this study exempt from review given subjects were obtained from a de-identified nationwide database.
Conflict-of-interest statement: None of the authors have relevant financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Lindsay A Sobotka, DO, Assistant Professor, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, 410 West 10th Avenue, Columbus, OH 43210, United States.
lindsay.sobotka@osumc.edu
Received: October 21, 2021
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
ARTICLE HIGHLIGHTS
Research background
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.
Research motivation
Currently, there is insufficient data examining the impact of CFTR modulators on the incidence of cirrhosis among patients with CF.
Research objectives
To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.
Research methods
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.
Research results
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).
Research conclusions
Patients treated with CFTR modulators have a lower incidence of cirrhosis compared to no treatment, ursodiol, or combination therapy.
Research perspectives
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.
