Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2022; 14(2): 411-419
Published online Feb 27, 2022. doi: 10.4254/wjh.v14.i2.411
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
Abstract
BACKGROUND

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.

AIM

To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.

METHODS

A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.

RESULTS

A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 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).

CONCLUSION

CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Keywords: Cirrhosis, Ursodiol, Transmembrane, Cystic fibrosis, Market scan, Cystic fibrosis related liver disease

Core Tip: The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on hepatobiliary outcomes in cystic fibrosis (CF) patients remains unknown. Utilizing a nationwide database, the incidence of cirrhosis in CF patients utilizing CFTR modulators, ursodiol, combination therapy or neither therapy was compared. A total of 7201 patients were studied including 12.6% on a CFTR modulator, 7.0% on ursodiol, 6.1% on combination therapy and 74.3% on neither therapy. Patients taking CFTR modulators had a lower incidence of cirrhosis than untreated patients (P = 0.05), or patients treated with Ursodiol (P < 0.001) or Ursodiol and CFTR modulators (P = 0.003). CFTR modulators may reduce the incidence of cirrhosis in patients with CF.