Highlights
• The total bile acid concentration as well as primary and secondary bile acids are elevated in children with cystic fibrosis.
• In contrast the concentration of taurine conjugated bile acids is decreased.
• These changes appear to aggravate with age, which could indicate an age-dependent increase in hepatobiliary impairment.
• The bile acid composition in patients with cystic fibrosis liver disease differs from the rest of the CF cohort.

Background
Approximately 20 percent of people with cystic fibrosis (CF) develop cystic fibrosis hepatobiliary involvement (CFHBI). Some show the more severe form advanced cystic fibrosis liver disease (aCFLD). The biliary tree is an important site for cystic fibrosis transmenbrane conductance regulator (CFTR) activity. Despite previous studies the impact of CFTR dysfunction on bile acid homeostasis, the composition of the different bile acids and its impact on hepatobiliary function remains unclear.
Methods
Between November 2020 and July 2022 serum samples from children with CF were collected. Bile acids were analysed by liquid chromatography coupled to tandem mass spectrometry. Serum samples from otherwise healthy patients hospitalised for elective procedures served as controls.
Results
73 children with CF, and 100 control patients were enrolled. Eight children of the CF cohort were diagnosed with aCFLD. In children with CF (n = 73), overall bile acid concentration as well as primary and secondary bile acids were significantly elevated, whereas the ratio of taurine conjugated bile acids was decreased. These alterations were not observed in infants and became more pronounced with age. Furthermore, children with aCFLD (n = 8, 11 %) showed significantly increased concentrations of secondary bile acids as well as lithocholic, glycolithocholic, deoxycholic and glycodeoxycholic acid.
Conclusions
Our data show that bile acid composition is altered in children with CF. This difference is evident from preschool age onward. Moreover, different bile acid compositions are detected in children with and without aCFLD. These changes appear to aggravate with age, which could indicate an age-dependent increase in hepatobiliary impairment.