Chenodeoxycholic acid stimulated fibroblast growth factor 19 response – a potential biochemical test for bile acid diarrhoea

C. Borup*, S. Wildt, J. J. Rumessen, P. N. Bouchelouche, J. Graff, M. Damgaard, C. McQuitty, D. Rainteau, L. K. Munck

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

Background: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. Aim: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. Methods: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry. Results: Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41–138] to 99 pg/mL (IQR: 67–147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54–512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42–79); 90 min: 48 pg/mL [IQR: 37–63); 150 min: 57 pg/mL (48–198)]. Receiver operating characteristics (ROCAUC) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROCAUC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation. Conclusions: The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.

OriginalsprogEngelsk
Sider (fra-til)1433-1442
Antal sider10
TidsskriftAlimentary Pharmacology and Therapeutics
Vol/bind45
Udgave nummer11
DOI
StatusUdgivet - jun. 2017

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