What is the diagnostic approach for bile acid diarrhea?

Diagnostic Approach for Bile Acid Diarrhea

In patients with chronic diarrhea after excluding other causes, diagnose bile acid diarrhea using SeHCAT testing (if available) or serum 7α-hydroxy-4-cholesten-3-one (C4), rather than empiric treatment trials. 1

Initial Clinical Context

Before pursuing bile acid diarrhea (BAD) testing, complete first-line evaluation to exclude other common causes:

• Screen for celiac disease with IgA tissue transglutaminase plus total IgA level (sensitivity and specificity >90%) 1, 2
• Test for Giardia using antigen test or PCR 1, 2
• Exclude inflammatory bowel disease with fecal calprotectin in patients under age 40 1
• Consider colonoscopy with biopsies from right and left colon (not rectum) to exclude microscopic colitis, which can coexist with BAD 1

High-Risk Populations for BAD

Strongly consider BAD testing in patients with:

• Terminal ileal resection or Crohn's disease affecting the ileum 1, 2
• Post-cholecystectomy diarrhea (>50% may have BAD) 1
• Pelvic radiotherapy or chemotherapy (>50% prevalence) 1
• Diarrhea-predominant IBS symptoms (up to 30% actually have BAD) 1
• Post-infectious diarrhea that persists 1

Preferred Diagnostic Tests

SeHCAT Testing (Gold Standard)

SeHCAT is the preferred test where available, with the highest diagnostic yield among all biomarkers for BAD 1:

• 7-day retention <15% indicates bile acid malabsorption 1
• Severity grading: <5% = severe, 5-10% = moderate, 10-15% = mild 1
• Predicts treatment response: 96% response to bile acid sequestrants with <5% retention, 80% with <10%, and 70% with <15% 1
• Limitations: Not available in North America, involves radiation exposure, expensive 1, 3

Serum 7α-Hydroxy-4-Cholesten-3-One (C4)

Use serum C4 as an alternative where SeHCAT is unavailable 1, 2:

• Cutoff value >47.1 ng/mL indicates bile acid diarrhea 1
• Negative predictive value 95%, positive predictive value 74% compared to SeHCAT 1
• Requires fasting sample due to diurnal and postprandial variation 1
• False positives occur in patients with liver disease 1

Alternative Tests (Limited Availability)

• 48-hour fecal bile acid measurement: Values >2300 μmol/48 hours indicate BAD, but cumbersome collection and not commercially available in many regions 1
• Serum FGF-19: Lower levels suggest BAD, but requires fasting and has diurnal variation 1

Critical Pitfall: Empiric Treatment Trials

The British Society of Gastroenterology strongly recommends against using empiric bile acid sequestrant trials instead of making a positive diagnosis 1:

• Lack of response to cholestyramine does not exclude BAD—44% of confirmed BAD patients fail cholestyramine alone, with half responding to colesevelam 1
• Empiric trials lead to diagnostic uncertainty and repeat unnecessary testing 1
• Exception: The AGA acknowledges empiric trials may be considered when commercial assays are unavailable, but this is a conditional recommendation with low-quality evidence 1

When BAD Testing is Negative or Unavailable

If SeHCAT or C4 testing is truly unavailable and empiric treatment is attempted:

• Use cholestyramine or colesevelam for 4-6 weeks 1
• Clinical response suggests but does not confirm BAD 1
• If no response, consider colesevelam as alternative (better tolerated) before abandoning diagnosis 1, 4
• Investigate other causes even if SeHCAT was abnormal, including small intestinal bacterial overgrowth, pancreatic insufficiency, or microscopic colitis 1

Diagnostic Algorithm Summary

1. Complete first-line chronic diarrhea workup (celiac, Giardia, inflammatory markers) 1, 2
2. Identify high-risk features for BAD (ileal disease, cholecystectomy, radiotherapy) 1, 2
3. Order SeHCAT if available (preferred test) 1
4. If SeHCAT unavailable, order fasting serum C4 1
5. Avoid empiric treatment trials unless no testing available 1
6. Consider colonoscopy with biopsies to exclude microscopic colitis, which frequently coexists 1