TY  - JOUR
A1  - Tabori, Harold
A1  - Schneider, Jochen
A1  - Lüth, Stefan
A1  - Zagoya, Carlos
A1  - Barucha, Anton
A1  - Lehmann, Thomas
A1  - Kauf, Eberhard
A1  - Barth, Astrid
A1  - Mainz, Jochen G.
T1  - Elevated levels of toxic bile acids in serum of cystic fibrosis patients with CFTR mutations causing pancreatic insufficiency
T2  - International journal of molecular sciences
N2  - Hepatobiliary involvement is a hallmark in cystic fibrosis (CF), as the causative CF Transmembrane Conductance Regulator (CFTR) defect is expressed in the biliary tree. However, bile acid (BA) compositions in regard to pancreatic insufficiency, which is present at an early stage in about 85% of CF patients, have not been satisfactorily understood. 
We assess the pattern of serum BAs in people with CF (pwCF) without CFTR modulator therapy in regard to pancreatic insufficiency and the CFTR genotype. 
In 47 pwCF, 10 free and 12 taurine- and glycine-conjugated BAs in serum were prospectively assessed. 
Findings were related to genotype, pancreatic insufficiency prevalence (PIP)-score, and hepatic involvement indicated by serum liver enzymes, as well as clinical and ultrasound criteria for CF-related liver disease. 
Serum concentrations of total primary BAs and free cholic acid (CA) were significantly higher in pwCF with higher PIP-scores (p = 0.025, p = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores >= 0.88 (p = 0.033) and with pancreatic insufficiency (p = 0.034). 
Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, p = 0.036). pwCF with severe CFTR genotypes, as assessed by the PIP-score, reveals more toxic BA compositions in serum. Subsequent studies assessing changes in BA homeostasis during new highly effective CFTR-modulating therapies are of high interest.
KW  - cystic fibrosis
KW  - CF liver disease
KW  - hepatic
KW  - biliary
KW  - bile acid
KW  - high performance liquid chromatography
Y1  - 2022
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/65401
SN  - 1422-0067
VL  - 23
IS  - 20
PB  - MDPI
CY  - Basel
ER  -