Introduction: Hepatobiliary disease occurs in up to 32% of people with cystic fibrosis (pwCF) before age 25 years. PwCF require liver transplantation for advanced cystic fibrosis-related liver disease (aCFLD) less commonly. In 2024, 14 pwCFnationwide (adult and pediatric) received a liver transplant. Despite the medical complexity and multi-system involvement of pwCF, there remains limited practice guidance informing liver transplant management in people with aCFLD.  

Methods: A multidisciplinary team with experience in CF reviewed endocrine, pulmonary, infectious disease, renal, gastrointestinal, nutrition, and surgical considerations that are unique to pwCF being evaluated for liver transplant. Special focus was applied to immunosuppression regimens in the setting of elexacaftor/tezacaftor/ivacaftor (ETI) use and long-term monitoring unique to pwCF including screening for colon cancer and CF-related diabetes (CFRD). 

Results:  The CF liver transplant guidance document was created and has been applied in the peritransplant period to two patients with aCFLD to guide steroid-sparing immunosuppression, CF-specific infection prophylaxis, and management of CF pulmonary disease peritransplant.  

Conclusion: We describe a single-center multisystem guidance document for the care of people with aCFLD undergoing liver transplant evaluation, with clinical application during two successful liver transplantations for aCFLD at our center. Given the relative rarity of liver transplant in this complex population, multi-center collaboration is needed to optimize a standardized approach to liver transplant care in people with aCFLD.