Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency
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 p...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Harold Tabori Jochen Schneider Stefan Lüth Carlos Zagoya Anton Barucha Thomas Lehmann Eberhard Kauf Astrid Barth Jochen G. Mainz |
| author_facet | Harold Tabori Jochen Schneider Stefan Lüth Carlos Zagoya Anton Barucha Thomas Lehmann Eberhard Kauf Astrid Barth Jochen G. Mainz |
| author_sort | Harold Tabori |
| collection | DOAJ |
| description | 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 <i>CFTR</i> 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 (<i>p</i> = 0.025, <i>p</i> = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 (<i>p</i> = 0.033) and with pancreatic insufficiency (<i>p</i> = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, <i>p</i> = 0.036). pwCF with severe <i>CFTR</i> 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. |
| first_indexed | 2024-03-09T20:06:16Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:06:16Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d81423af9a064987b5397228eb36cf3b2023-11-24T00:31:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201243610.3390/ijms232012436Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic InsufficiencyHarold Tabori0Jochen Schneider1Stefan Lüth2Carlos Zagoya3Anton Barucha4Thomas Lehmann5Eberhard Kauf6Astrid Barth7Jochen G. Mainz8Cystic Fibrosis Center, Brandenburg Medical School (MHB) University, Klinikum Westbrandenburg, 14770 Brandenburg an der Havel, GermanyCystic Fibrosis Centre, Jena University Hospital, 07740 Jena, GermanyDepartment of Gastroenterology, Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, GermanyCystic Fibrosis Center, Brandenburg Medical School (MHB) University, Klinikum Westbrandenburg, 14770 Brandenburg an der Havel, GermanyCystic Fibrosis Center, Brandenburg Medical School (MHB) University, Klinikum Westbrandenburg, 14770 Brandenburg an der Havel, GermanyInstitute of Medical Statistics, Jena University Hospital, 07743 Jena, GermanyCystic Fibrosis Centre, Jena University Hospital, 07740 Jena, GermanyInstitut für Pharmakologie und Toxikologie, Jena University Hospital, 07743 Jena, GermanyCystic Fibrosis Center, Brandenburg Medical School (MHB) University, Klinikum Westbrandenburg, 14770 Brandenburg an der Havel, GermanyHepatobiliary 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 <i>CFTR</i> 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 (<i>p</i> = 0.025, <i>p</i> = 0.009, respectively). Higher total BAs were seen in pwCF with PIP-scores ≥0.88 (<i>p</i> = 0.033) and with pancreatic insufficiency (<i>p</i> = 0.034). Free CA was higher in patients with CF-related liver involvement without cirrhosis, compared to pwCF without liver disease (2.3-fold, <i>p</i> = 0.036). pwCF with severe <i>CFTR</i> 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.https://www.mdpi.com/1422-0067/23/20/12436cystic fibrosisCF liver diseasehepaticbiliarybile acidhigh performance liquid chromatography |
| spellingShingle | Harold Tabori Jochen Schneider Stefan Lüth Carlos Zagoya Anton Barucha Thomas Lehmann Eberhard Kauf Astrid Barth Jochen G. Mainz Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency International Journal of Molecular Sciences cystic fibrosis CF liver disease hepatic biliary bile acid high performance liquid chromatography |
| title | Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency |
| title_full | Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency |
| title_fullStr | Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency |
| title_full_unstemmed | Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency |
| title_short | Elevated Levels of Toxic Bile Acids in Serum of Cystic Fibrosis Patients with <i>CFTR</i> Mutations Causing Pancreatic Insufficiency |
| title_sort | elevated levels of toxic bile acids in serum of cystic fibrosis patients with i cftr i mutations causing pancreatic insufficiency |
| topic | cystic fibrosis CF liver disease hepatic biliary bile acid high performance liquid chromatography |
| url | https://www.mdpi.com/1422-0067/23/20/12436 |
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