Diagnostic Tests for Bile Acid Diarrhea
The SeHCAT (75Se-homotaurocholic acid) retention test is the preferred diagnostic test for bile acid diarrhea where available, with 7-day retention <15% indicating bile acid malabsorption. 1, 2
Primary Diagnostic Tests
SeHCAT Test (Gold Standard in Europe/UK)
- The SeHCAT test involves oral administration of radiolabeled synthetic bile acid with gamma camera imaging at day 7 to measure retention. 1
- Retention values <15% indicate bile acid malabsorption, with severity grading as follows: <5% = severe, 5-10% = moderate, 10-15% = mild. 1, 2
- Treatment response correlates with severity: 96% respond to bile acid sequestrants with <5% retention, 80% with <10%, and 70% with <15%. 2
- This test is widely used in Europe but not available in North America. 1
- The SeHCAT test has the highest diagnostic yield among all biomarkers for bile acid diarrhea. 2
Alternative Tests (Available in North America)
Serum C4 (7α-hydroxy-4-cholesten-3-one)
- Serum C4 measures bile acid synthesis and is recommended as an alternative where SeHCAT is unavailable. 1, 2
- This test avoids radiolabels and correlates with SeHCAT results, though the standard material is not commercially available in many locations. 1
- C4 levels >28 ng/ml suggest increased bile acid synthesis consistent with bile acid malabsorption. 3
Serum Fibroblast Growth Factor 19 (FGF19)
- FGF19 measures defective feedback of bile acid synthesis and is available in the United States. 1
- FGF19 and C4 are significantly inversely related (r=-0.64), with lower FGF19 values indicating bile acid malabsorption. 3
- FGF19 <145 pg/ml has 58% sensitivity and 79% specificity for detecting elevated C4 >28 ng/ml. 3
48-Hour Fecal Bile Acid Measurement
- Total bile acid measurement in a 48-hour stool collection documents increased fecal bile acids and is available in North America. 1
- Recent advances include assays of primary bile acids in addition to total bile acids. 1
- This test quantifies excreted bile acids directly but requires prolonged stool collection. 1
Older/Less Used Tests
14C-Glycocholate Breath Test
- This breath test measures bacterial deconjugation of bile salts, but sensitivity and specificity are generally poor. 1
14C-Glycocholate Fecal Recovery
- This involves quantifying fecal recovery of 14C-glycocholate over 48-72 hours after oral administration. 1
Critical Clinical Pitfall: Empiric Treatment Trials
Empiric bile acid sequestrant trials should NOT replace definitive diagnostic testing. 2
- The British Society of Gastroenterology strongly recommends against using empiric trials instead of making a positive diagnosis. 2
- Lack of response to cholestyramine does not exclude bile acid diarrhea—44% of confirmed cases fail cholestyramine alone, with half responding to colesevelam. 2
- Empiric trials lead to diagnostic uncertainty and unnecessary repeat testing. 2
- However, when diagnostic tests are unavailable, a therapeutic trial may be considered, though its value has not been formally studied. 1
High-Risk Populations Requiring Testing
Testing should be strongly considered in specific high-risk groups: 2
- Terminal ileal resection or Crohn's disease affecting the ileum (90% of patients with ileal resection have abnormal SeHCAT <5%). 1, 2
- Post-cholecystectomy diarrhea (>50% may have bile acid diarrhea). 2
- Pelvic radiotherapy or chemotherapy (>50% prevalence). 2
- Diarrhea-predominant IBS symptoms (up to 30% actually have bile acid diarrhea). 1, 2
Recommended Diagnostic Algorithm
Before testing for bile acid diarrhea, exclude other causes: 2
- Screen for celiac disease with IgA tissue transglutaminase plus total IgA level. 2
- Test for Giardia using antigen test or PCR. 2
- Exclude inflammatory bowel disease with fecal calprotectin in patients under age 40. 2
- Consider colonoscopy with biopsies from right and left colon (not rectum) to exclude microscopic colitis, which can coexist with bile acid diarrhea. 2