Comparison of ⁷⁵SeHCAT Retention Half-Life and Fecal Content of Individual Bile Acids in Patients with Chronic Diarrheal Disorders

Abstract

Measurement of the retention of 23–⁷⁵Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn’s disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 μCi SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15–10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3–33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2–24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28–216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Bile Acid Diarrhea

“…The whole-body half-life of the tracer can be calculated and compared to controls. The result correlates well with analysis of fecal bile acids but is easier to perform [28,46]. Any source of malabsorption will result in a shortened half-life and this test is more sensitive than the 14 C-cholylglycine breath test and more conveniently employed.…”

Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor

“…4 5 7 8 Patients with IBD have increased faecal excretion of bile salts and decreased absorption of the orally ingested radiolabelled bile acid 75 Se-homotaurocholic acid. 6 In a rabbit model, intestinal inflammation decreased ileal ASBT mRNA levels and experimental ileitis in hamsters decreased active bile acid uptake by 84%. 38 39 The rat ASBT promoter is suppressed by cytokines through binding of a c-fos/c-jun heterodimer to an AP-1 element.…”

“…3 A more common clinical entity associated with intestinal bile acid malabsorption is inflammatory bowel disease (IBD), particularly Crohn's disease. [4][5][6][7][8] Intestinal bile acid absorption is a major determinant of the amount of bile acids that return to the liver and consequently of the bile acid pool size. 9 Faecal bile acid loss can be partly compensated for by de novo hepatic synthesis; however, patients with Crohn's disease have increased bilirubin secretion rates into bile and an increased risk of pigment gall stone formation, presumably due to increased colonic bile salt levels, which solubilise unconjugated bilirubin, prevent calcium complexing, and promote its absorption and enterohepatic cycling.…”

Human Apical Sodium-dependent Bile Salt Transporter Gene (SLC10A2) Is Regulated by the Peroxisome Proliferator-activated Receptor α

“…This feature has led to the evaluation of PPAR␥ ligands such as the thiazolidinedione derivatives as a treatment option in inflammatory bowel disease (IBD) (50). Patients with IBD have increased fecal excretion of bile salts and decreased absorption of the orally ingested radiolabeled bile acid 75 Se-homotaurocholic acid (51). Simultaneous activation of PPAR␣ by novel therapeutic PPAR␥ ligands in IBD could correct the bile salt absorptive defect by inducing ASBT expression.…”