- MeSH
- Autoimmune Diseases diagnosis complications therapy MeSH
- Liver Cirrhosis, Biliary diagnosis etiology therapy MeSH
- Cholangiopancreatography, Endoscopic Retrograde methods MeSH
- Diagnostic Techniques, Digestive System * MeSH
- Drug Therapy * MeSH
- Gastrointestinal Neoplasms diagnosis complications MeSH
- Immunologic Tests methods MeSH
- Comorbidity MeSH
- Chenodeoxycholic Acid administration & dosage adverse effects therapeutic use MeSH
- Ursodeoxycholic Acid administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Cholangiopancreatography, Magnetic Resonance methods MeSH
- Pruritus complications therapy MeSH
- Liver Failure therapy MeSH
- Cholangitis, Sclerosing * diagnosis etiology therapy MeSH
- Statistics as Topic MeSH
- Liver Transplantation methods trends MeSH
- Colitis, Ulcerative diagnosis complications MeSH
- Ultrasonography methods MeSH
- Check Tag
- Humans MeSH
- MeSH
- Hepatitis, Autoimmune * diagnosis etiology therapy MeSH
- Azathioprine administration & dosage adverse effects therapeutic use MeSH
- Liver Cirrhosis, Biliary diagnosis etiology therapy MeSH
- Cholangitis * diagnosis etiology therapy MeSH
- Cholestasis * diagnosis etiology therapy MeSH
- Diagnostic Techniques, Digestive System classification trends MeSH
- Diagnostic Imaging methods MeSH
- Diagnosis, Differential MeSH
- Drug Therapy methods MeSH
- Disease Attributes MeSH
- Comorbidity MeSH
- Chenodeoxycholic Acid administration & dosage adverse effects therapeutic use MeSH
- Ursodeoxycholic Acid administration & dosage adverse effects therapeutic use MeSH
- Humans MeSH
- Prednisone administration & dosage adverse effects therapeutic use MeSH
- Pruritus diagnosis complications therapy MeSH
- Cholangitis, Sclerosing diagnosis etiology therapy MeSH
- Statistics as Topic MeSH
- Liver Transplantation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.
- MeSH
- Administration, Oral MeSH
- Cholestenones blood MeSH
- Adult MeSH
- Fibroblast Growth Factors blood metabolism MeSH
- Liver metabolism MeSH
- Clinical Protocols MeSH
- Chenodeoxycholic Acid administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Cathartics administration & dosage MeSH
- Aged MeSH
- Cholangitis, Sclerosing blood drug therapy metabolism MeSH
- Intestines metabolism MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
