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P217 The role of 7-alfa-hydroxy-4-cholesten-3-one (C4) as a biomarker for bile acid malabsorption in inflammatory bowel disease and microscopic colitis

I. Lyutakov MD1, V. Lozanov2, P. Sugareva2, R. Nakov1, H. Valkov1, A. Dimov3, B. Vladimirov1, P. Penchev1

1Department of Gastroenterology, University Hospital ‘Tsaritsa Yoanna - ISUL’, Sofia, Bulgaria, 2Department of Medical Chemistry and Biochemistry, Medical University Sofia, Sofia, Bulgaria, 3Department of Statistics and Econometrics, University of National and World Economy, Sofia, Bulgaria

Background

Bile acid diarrhoea (BAD) is a condition when excessive bile acids (BAs) enter the colon due to bile acid malabsorption (BAM). Impaired metabolism of BAs and BAM interaction are involved in the pathophysiology of microscopic colitis (MC) and inflammatory bowel disease (IBD), especially in Crohn’s disease (CD). Plasma levels of 7-alfa-hydroxy-4-cholesten-3-one (C4) is a new biomarker of BA synthesis. Little is known about the mechanisms of BAs dysregulation and levels of C4 in patients with IBD, irritable bowel syndrome (IBS-D) and microscopic colitis (MC).

Methods

The aim was to evaluate the diagnostic accuracy of plasma levels of C4 for finding BAM in patients with IBD, IBS-D and MC. We enrolled 109 adult patients with chronic diarrhoea and 11 healthy controls who underwent standard laboratory tests, colonoscopy, serum C4 and faecal calprotectin (FC). Patients were split into six groups: 30 patients with active IBD, 21 patients with IBD in remission reporting a high number of bowel movements per day, 21 patients with IBD after surgery (ileal resection), 23 patients with IBS- D, 14 patients with MC and 11 healthy subjects (controls). Fasting serum C4 were measured by high-performance liquid chromatography (HPLC) analysis and FC by the quantitative immunochromatographic method.

Results

Based on cut-off levels of C4 (above 48.4 ng/ml) diagnosis of BAM was confirmed in 66 of 109 patients (60.5%) and excluded in 43 patients (39.4%) compare to healthy controls. Median levels of C4 in patients with IBD active were 53.1 ng/ml, IBD remission was 52.2 ng/ml, IBD after surgery was 85.7 ng/ml, IBS-D were 7.5 ng/ml, MC was 69.3 ng/ml and healthy controls were with 3.7 ng/ml. A cut-off concentration of C4 of 48.4 ng/ml or higher identified patients with MC and IBD with diarrhoea attributable to BAM with an AUROC 0.89 and sensitivity 79.8%, specificity 90.9%, positive predictive value (PPV) of 96.1% and negative predictive value (NPV) of 88.6% compared with healthy controls (p < 0.001). IBD patients in remission (FC < 100 µg/g) with up to 4 bowel movements daily was n = 16 (76.2%) and concentration of C4 above 48.4 ng/ml were found in n = 13 (61%) of the patients.

Conclusion

BAM in IBD and MC is a common and very under-diagnosed condition. Serum C4 could be used for screening biomarker for BAM in patients with IBD, IBD after surgery (ileal resection) and MC. We found that serum concentrations of C4 above 48.4 ng/ml identify patients with diarrhoea likely attributable to BAM with high diagnostic accuracy and IBD patients in remission with found bile acid diarrhoea can benefit from additional treatment with bile acid binders. Further bigger studies are needed to establish the efficacy of serum C4 in patients with suspected BAM in IBD and MC.