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P182 Stimulation with chenodeoxycholic acid and meal may increase power of biochemical tests for diagnosis of bile acid diarrhoea

C. Borup*1, S. Wildt2, M. Damgaard3, J. Graff3, P. Nordine Bouchelouche4, D. Rainteau5, J. J. Rumessen6, L. K. Munck7, 8

1Hvidovre University Hospital, Dept. of Medical Gastroenterology, Hvidovre, Denmark, 2Køge University Hospital, Medical Department, Køge-4600, Denmark, 3Hvidovre University Hospital, Clinical Physiology and Nuclear Medicine, Hvidovre, Denmark, 4Køge University Hospital, Clinical Biochemistry, Køge, Denmark, 5Sorbonne University - UPMC, Clinical Biochemistry, Paris, France, 6Gentofte University Hospital, Research Unit, Gentofte, Denmark, 7Køge University Hospital, Medical Department, Køge, Denmark, 8University of Copenhagen, Department of Medical Physiology, Copenhagen, Denmark

Background

Bile acid diarrhoea (BAD) is a common and overlooked cause of chronic watery diarrhoea. Access to SeHCAT for diagnosis is limited. Patients with idiopathic BAD have lower serum levels of fibroblast growth factor 19 (FGF19), but the diagnostic value of fasting FGF19 is limited. FGF19 measured postprandially or following stimulation by chenodeoxycholic acid (CDCA) may have better discriminative power. High levels of 7α-hydroxy-4-cholesten-3-on (C4) in plasma is associated with BAD, but analysis requires high-performance liquid chromatography (HPLC) or tandem mass spectrometry.

Methods

Included were 8 patients with newly diagnosed idiopathic BAD and 8 healthy volunteers. Sequestrates were discontinued 1 week before the study. On 3 separate days, fasting blood samples were collected before each of 3 stimuli: standardised breakfast (toast and eggs), 2g of oral CDCA, and breakfast + 2g of oral CDCA. Blood was drawn repeatedly for 4 hours. FGF19 was analysed by ELISA assay, and C4 and bile acid species were analysed by HPLC.

Results

BAD patients had more stools per day, 2.5 (median, IQR 1.8–3.3) vs 1.0 (1.0–1.3); p < 0.05), and looser stools Bristol 5.6 (4.7–5.9) vs 4.0 (3.5–4.3); p < 0.05). I-BAD patients had SeHCAT ≤ 10%. After meal stimulation, FGF19 differed between groups at 60 to 120 minutes (p < 0.05) with a receiver operated characteristics (ROC) 120 minutes postprandially of 0.70. After breakfast and CDCA stimulation, plasma CDCA peaked at 60 minutes, with higher values in healthy volunteers (p = 0.011). After breakfast + CDCA stimulation FGF19 decreased, from median 56 pg/mL to 48 pg/mL in BAD patients after 90 minutes (p = 0.017), and increased in controls, from median 62 pg/mL to 99 pg/mL (p = 0.012) with ROC 0.84 (95% CI 0.64–1.0). The 90-minute FGF19 values minus fasting FGF19 values separated BAD patients from healthy volunteers (p = 0.001) and a ROC of 1.0.

Figure 1. ROC curves. Fasting (FGF19–0) with area under the curve (AUC) of 0.55. FGF19–90: 90 minutes after meal, and chenodeoxycholic acid; AUC of 0.84. Diff. 90t0 is FGF19 at 90 minutes minus fasting FGF19 AUC of 1.0.

No stimulus affected C4, which consistently was lower in healthy volunteers than in I-BAD and ROC analysis of fasting C4 gave AUC 0.88, and C4 > 2.5 µM had a sensitivity of 83.3% and specificity of 87.5%.

Figure 2. ROC curve for all fasting values of C4. Area under the curve is 0.88. C4 values > 12.6µM have 83.3% sensitivity for bile acid diarrhoea (BAD) and 87.5% specificity for BAD.

Conclusion

Elevated C4 is a marker of I-BAD in patients with SeHCAT verified BAD. Combined stimulation with meal and CDCA improves the discriminative properties of FGF19 for BAD. Larger and prospective trials are needed.