Clinical management and outcomes of hepatobiliary disease in the cystic fibrosis transmembrane conductance regulator modulator era.

PURPOSE OF REVIEW: Multiple cystic fibrosis transmembrane conductance regulator (CFTR) modulators are approved for the treatment of cystic fibrosis (CF) and show significant improvement in lung function, BMI, quality of life, and sweat chloride. However, their ability to impact liver disease is unclear. This review highlights the current published literature on CFTR modulators and liver health and briefly reviews considerations for clinical management of hepatobiliary disease in the CFTR modulator era.

RECENT FINDINGS: Currently, the primary data available on the clinical efficacy of CFTR modulators on CF hepatobiliary involvement (CFHBI) or advanced CF liver disease (aCFLD) is from small to moderate sized single-center studies, although more recently large, multicenter studies are emerging. Studies report opposing changes in aminotransferases, and mixed liver fibrosis index and elastography results. Yet, in total CFTR modulators generally do not worsen liver disease and may improve it in some individuals. Additional clinical management considerations are necessary in those on CFTR modulators who received an organ transplant or during nutritional evaluations.

SUMMARY: To better understand the possible benefit of CFTR modulator therapies on hepatobiliary health, additionally larger, longer-term, multicenter studies with sub-group phenotyping are necessary. Until then, providers should watch for liver-related adverse events, and be cognizant on how CFTR modulators may impact areas of clinical care for individuals with CF.