We have located links that may give you full text access.
IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients with an S1251N or a G551D gating mutation.
Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society 2018 September 30
OBJECTIVE: Disruption of the enterohepatic circulation of bile acids (BAs) is part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, improves pulmonary function in CF patients with class III gating mutations. We studied the effect of ivacaftor on the enterohepatic circulation by assessing markers of BA homeostasis and their changes in CF patients.
METHODS: In CF patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor.
RESULTS: At baseline, median FGF19 was lower (52% and 53%, P < .001) and median C4 higher (350% and 364%, P < .001), respectively, for the S1251 N and G551D mutation patient groups compared to healthy controls. Treatment with ivacaftor significantly increased FGF19 and reduced C4 levels towards normalization in both cohorts but this did not correlate with CFTR function in other organs, as measured by sweat chloride levels or pulmonary function.
CONCLUSIONS: We demonstrate that patients with CFTR gating mutations display interruption of the enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels. Treatment with ivacaftor partially restored this disruption of BA homeostasis. The improvement did not correlate with established outcome measures of CF, suggesting involvement of modulating factors of CFTR correction in different organs.
METHODS: In CF patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor.
RESULTS: At baseline, median FGF19 was lower (52% and 53%, P < .001) and median C4 higher (350% and 364%, P < .001), respectively, for the S1251 N and G551D mutation patient groups compared to healthy controls. Treatment with ivacaftor significantly increased FGF19 and reduced C4 levels towards normalization in both cohorts but this did not correlate with CFTR function in other organs, as measured by sweat chloride levels or pulmonary function.
CONCLUSIONS: We demonstrate that patients with CFTR gating mutations display interruption of the enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels. Treatment with ivacaftor partially restored this disruption of BA homeostasis. The improvement did not correlate with established outcome measures of CF, suggesting involvement of modulating factors of CFTR correction in different organs.
Full text links
Trending Papers
A Personalized Approach to the Management of Congestion in Acute Heart Failure.Heart International 2023
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium-Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.International Journal of Molecular Sciences 2024 Februrary 21
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app