When should a SeHCAT (75Se‑hydroxyselenocholyl‑taurine) test be ordered for chronic watery diarrhoea after negative work‑up for infection, inflammatory bowel disease, celiac disease, or medication‑induced diarrhoea, and what are the interpretation criteria and subsequent management?

SeHCAT Test for Chronic Watery Diarrhoea

When to Order SeHCAT Testing

Order a SeHCAT test in patients with chronic watery diarrhoea after excluding infection, inflammatory bowel disease, celiac disease, and medication-induced causes, particularly when specific risk factors for bile acid malabsorption are present. 1

High-Priority Indications for Testing

• Terminal ileal disease or resection: Over 90% of patients with terminal ileal resection demonstrate abnormal SeHCAT retention, making this the strongest indication for testing 1
• Post-cholecystectomy diarrhoea: Up to 10% develop chronic diarrhoea through bile acid malabsorption 2
• Post-infectious diarrhoea: Well-documented association with subsequent bile acid malabsorption 1
• Crohn's disease in remission: Test when patients have ileal involvement without objective evidence of active inflammation but persistent diarrhoea 1, 3
• Idiopathic chronic diarrhoea or IBS-D: After negative first-line investigations, as approximately one-third of these patients have bile acid malabsorption 1
• Post-radiation therapy: Increasingly common given the three-fold rise in cancer survivors 1

Testing Sequence

The SeHCAT test should be positioned as a second-line investigation after basic screening has excluded common causes 1, 4. First-line testing must include complete blood count, C-reactive protein, IgA tissue transglutaminase with total IgA, faecal calprotectin, and Giardia testing 4, 3.

Test Methodology and Interpretation

How the Test Works

The patient ingests 75Se-homotaurocholic acid (a synthetic analogue of natural conjugated bile acid taurocholic acid), and retained radioactivity is measured by gamma camera at 7 days 1.

Interpretation Criteria

• Normal retention: ≥15% at 7 days 1
• Mild bile acid malabsorption: 10-15% retention 1
• Moderate bile acid malabsorption: 5-10% retention 1
• Severe bile acid malabsorption: <5% retention 1

Predictive Value for Treatment Response

Patients with SeHCAT retention <5% have the highest treatment response rates, with all patients in this category responding to cholestyramine in key studies. 1, 5

• <5% retention: Nearly 100% response to bile acid sequestrants 1, 5
• 5-10% retention: Approximately 38% response rate 1
• 10-15% retention: Minimal response (symptoms often compatible with IBS rather than true bile acid malabsorption) 1
• >15% retention: Only 15% response to treatment 5

Alternative Diagnostic Approaches

When SeHCAT is Unavailable

Use serum C4 (7α-hydroxy-4-cholesten-3-one) assay as the alternative diagnostic test when SeHCAT is not available. 1, 4

• Serum C4 correlates well with SeHCAT results and avoids radiolabels 1
• Sensitivity 40% and specificity 85% when compared to 48-hour faecal bile acid measurement 1
• FGF19 assay has lower diagnostic accuracy (sensitivity 20%, specificity 75%) and cannot be recommended over C4 1

Empiric Treatment Trial

Empiric trials of cholestyramine may be considered when neither SeHCAT nor C4 testing is available, though formal diagnosis is strongly preferred. 1, 4

The British Society of Gastroenterology guidelines note that "the value of this approach has not been the subject of study" 1, and the 2018 guidelines emphasize making a positive diagnosis rather than blind empirical therapy 1.

Subsequent Management Based on Results

For Positive SeHCAT Results (<15% retention)

Start cholestyramine 4g once or twice daily with meals, titrating gradually to 2-12g/day based on symptom response. 2, 3

• Begin with gradual dose titration to minimize side effects (bloating, constipation, drug interactions) 3
• Approximately 70% of patients achieve clinical response overall 2
• Response rates approach 100% when retention is <5% 1, 5
• Alternative sequestrants (colesevelam or colestipol) can be used if cholestyramine is not tolerated 2, 3

For Negative SeHCAT Results (≥15% retention)

• Only 15% of patients with normal SeHCAT respond to bile acid sequestrants 5
• Pursue alternative diagnoses including microscopic colitis (requires colonoscopy with biopsies from right and left colon, not rectum) 1
• Consider lactose malabsorption, small bowel bacterial overgrowth, or functional diarrhoea 1

Critical Pitfalls to Avoid

• Do not assume terminal ileal resection patients need testing before treatment: Given the extremely high pretest probability (>90%), diagnostic testing may not be necessary before initiating bile acid sequestrants in documented ileal resection 2
• Do not use bile acid sequestrants in extensive ileal resection (>100cm): These patients have fat malabsorption rather than bile acid diarrhoea and require different management 2, 3
• Do not rely on symptom presentation alone: No symptoms reliably predict bile acid diarrhoea diagnosis 3
• Do not overlook coexisting conditions: Treat underlying Crohn's disease, microscopic colitis, or small intestinal bacterial overgrowth in addition to bile acid diarrhoea therapy when these conditions coexist 3
• Do not assume Rome IV criteria exclude organic disease: These criteria have only 52-74% specificity and do not reliably exclude bile acid diarrhoea 4, 3

Diagnostic Yield

Studies demonstrate that 56% of patients with unexplained chronic diarrhoea after full investigation have abnormal SeHCAT retention, making this a high-yield second-line test 5. In idiopathic chronic diarrhoea or IBS-D specifically, approximately one-third have evidence of bile acid malabsorption 1.