©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
Decoding liver injury in cystic fibrosis: How to tell drug-induced liver injury from cystic fibrosis liver disease
Junseo Lee, Anuroop Yekula, Ava Wexler, William Zhuang, Ashwath Elangovan, Joshua Rosario, Philomena Burger, Gopal Ramaraju, Benyam Addissie, Nicholas Lim, Michael R Narkewicz, Patrick Twohig
Junseo Lee, Anuroop Yekula, Patrick Twohig, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14682, United States
Ava Wexler, Department of Internal Medicine, University of Rochester Medical Center, Rochester, NY 14682, United States
William Zhuang, Ashwath Elangovan, Joshua Rosario, Philomena Burger, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14682, United States
Gopal Ramaraju, Benyam Addissie, Nicholas Lim, Department of Transplant Hepatology, University of Rochester Medical Center, Rochester, NY 14682, United States
Michael R Narkewicz, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, United States
Author contributions: Twohig P designed the overall concept and outline of the manuscript; Lee J, Yekula A, Wexler A, Zhuang W, Elangovan A, Rosario J, Burger P, and Twohig P conducted the literature review and drafted the manuscript; Lee J, Yekula A, Narkewicz MR, Ramaraju G, Lim N, Addissie B, and Twohig P made critical revisions; all authors approved the final version to publish.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Patrick Twohig, MD, Assistant Professor, FRCPC, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14682, United States.
patrick_twohig@urmc.rochester.edu
Received: October 11, 2025
Revised: December 11, 2025
Accepted: January 8, 2026
Published online: March 14, 2026
Processing time: 151 Days and 13.6 Hours
BACKGROUND
Cystic fibrosis liver disease (CFLD) is a significant comorbidity in individuals with cystic fibrosis (CF), marked by biliary fibrosis and progressive cholestasis. The advent of CF transmembrane conductance regulator (CFTR) modulators has revolutionized care for lung disease, but their impact on liver-specific disease and outcomes remain unclear. Additionally, the risk of comorbid cholestatic liver injury from medications and progression of CFLD complicates the diagnostic landscape.
AIM
To provide a clinical framework for differentiating CFLD and drug induced liver injury (DILI), including from CFTR modulators.
METHODS
A comprehensive literature review was conducted using PubMed, EMBASE, and Cochrane Library databases through March 2025. Studies evaluating pathogenesis, clinical features, diagnostic strategies, and management of CFLD and CFTR modulator-related DILI were included. Data were synthesized to highlight distinguishing clinical and histopathologic features and to guide evidence-based management.
RESULTS
CFLD typically presents with insidious progression, portal hypertension, and biliary cirrhosis, whereas CFTR modulator-induced DILI often manifests acutely with jaundice, elevated liver enzymes, and a temporal association with therapy initiation. Key differentiators include biochemical patterns, imaging findings, response to drug withdrawal, and, when necessary, liver histology. Management strategies range from dose modification and supportive care in DILI to ursodeoxycholic acid, nutritional optimization, and portal hypertension management in CFLD.
CONCLUSION
Early recognition and differentiation between DILI and underlying CFLD are essential for optimizing therapy, preserving liver function, and guiding long-term management in patients with CF. As CFTR modulators become the cornerstone of CF management, vigilance for hepatotoxicity is critical. A multidisciplinary approach involving hepatology and CF care teams is recommended.
Core Tip: Cystic fibrosis (CF) liver disease is a major comorbidity in CF, complicated by progressive cholestasis and overlapping risk of drug-induced liver injury, including from CF transmembrane conductance regulator modulators. This study synthesizes literature on pathogenesis, clinical features, diagnostics, and management to aid in distinguishing advanced CF liver disease progression from drug induced liver injury. Key differentiators include biochemical profiles, imaging, treatment response, and histology. Early recognition and a multidisciplinary approach are essential to optimize therapy, preserve liver function, and balance the benefits and risks of CF transmembrane conductance regulator modulators.
