How do you diagnose bile acid diarrhea?

Diagnostic Approach to Bile Acid Diarrhea

For patients with chronic diarrhea, a positive diagnosis of bile acid diarrhea should be made using either SeHCAT testing or serum 7α-hydroxy-4-cholesten-3-one (C4) measurement, rather than empiric treatment trials. 1

Diagnostic Tests for Bile Acid Diarrhea

First-line Tests (in order of preference)

1. SeHCAT scan (75selenium homocholic acid taurine)

   • Gold standard test with highest diagnostic yield 1
   • Retention values interpretation:
     • 10-15% = mild bile acid loss
     • 5-10% = moderate bile acid loss
     • 0-5% = severe bile acid loss 1
   • Predicts response to therapy with bile acid sequestrants 1
   • Limited availability in North America 1

2. Serum 7α-hydroxy-4-cholesten-3-one (C4)

   • Measures bile acid synthesis
   • Requires fasting sample
   • Diagnostic thresholds:

     • 47.1 ng/mL is indicative of bile acid diarrhea 1

     • <15 ng/mL has 85% negative predictive value 2

     • 48 ng/mL has 82% positive predictive value 2

   • 95% negative predictive value compared to SeHCAT 1
   • Subject to diurnal variation; false positives can occur in liver disease 1

3. Serum Fibroblast Growth Factor 19 (FGF-19)

   • Lower levels correlate with bile acid diarrhea
   • Less accurate than C4 or SeHCAT 3
   • Sensitivity and specificity at 145 pg/ml cutoff: 58% and 79% respectively 3
   • Requires fasting sample and subject to diurnal variation 1

4. Fecal Bile Acid Measurement

   • Values >2300 μmol/48 hours indicate bile acid diarrhea 1
   • Requires 48-hour stool collection
   • Cumbersome and not widely available 1
   • Affected by dietary fat intake 1

When to Test for Bile Acid Diarrhea

Testing for bile acid diarrhea is recommended in the following scenarios:

• Patients with chronic diarrhea (AGA conditional recommendation) 1
• Patients with diarrhea-predominant IBS or functional diarrhea (up to 30% have bile acid diarrhea) 1
• Patients with risk factors:
  • Terminal ileal resection or disease (e.g., Crohn's disease) 1
  • Post-cholecystectomy diarrhea 1
  • History of abdominal/pelvic radiotherapy (>50% have bile acid diarrhea) 1
  • Post-infectious diarrhea 1

Diagnostic Algorithm

1. Initial evaluation: Rule out other causes of chronic diarrhea

   • Screen for celiac disease (IgA tissue transglutaminase) 1
   • Test for inflammation (fecal calprotectin or lactoferrin) 1
   • Test for Giardia 1
   • Consider colonoscopy with biopsies to exclude microscopic colitis 1

2. Bile acid diarrhea testing:

   • If SeHCAT available: Perform test (abnormal if ≤10%)
   • If SeHCAT unavailable: Measure serum C4 (abnormal if >47.1 ng/mL)
   • If neither available: Consider FGF-19 or fecal bile acid measurement

3. Management based on test results:

   • Positive test: Initiate bile acid sequestrant therapy
   • Negative test: Investigate other causes of diarrhea

Common Pitfalls to Avoid

1. Empiric treatment without testing: The British Society of Gastroenterology strongly recommends against empiric trials of bile acid sequestrants without diagnostic testing 1

2. Misinterpreting negative response to cholestyramine: Lack of response to cholestyramine does not exclude bile acid diarrhea; consider alternative sequestrants like colesevelam 1

3. Overlooking bile acid diarrhea in IBS-D: Up to 30% of patients diagnosed with IBS-D actually have bile acid diarrhea 1

4. Ignoring other causes: Even with confirmed bile acid diarrhea, consider additional diagnoses (bacterial overgrowth, pancreatic insufficiency, microscopic colitis) if symptoms persist despite treatment 1

5. Using inappropriate cutoffs: Different diagnostic tests have specific thresholds; using incorrect cutoffs may lead to misdiagnosis 2

Bile acid diarrhea remains underdiagnosed despite being a common condition affecting approximately 1% of the population 4. Using appropriate diagnostic testing rather than empiric treatment trials is essential for proper diagnosis and management of this treatable condition.