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

Aliment Pharmacol Ther. 2017 Jun;45(11):1433-1442. doi: 10.1111/apt.14056. Epub 2017 Apr 5.

Abstract

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.

MeSH terms

  • Adult
  • Bile Acids and Salts / metabolism*
  • Case-Control Studies
  • Chenodeoxycholic Acid / administration & dosage*
  • Cholestenones / metabolism
  • Diarrhea / diagnosis*
  • Enzyme-Linked Immunosorbent Assay
  • Fasting
  • Female
  • Fibroblast Growth Factors / blood*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies

Substances

  • Bile Acids and Salts
  • Cholestenones
  • FGF19 protein, human
  • Chenodeoxycholic Acid
  • 7 alpha-hydroxy-4-cholesten-3-one
  • Fibroblast Growth Factors