What is the diagnosis and treatment of bile acid diarrhea?

Diagnosis and Treatment of Bile Acid Diarrhea

For patients with chronic diarrhea, SeHCAT testing is the preferred diagnostic test for bile acid diarrhea where available, with 7-day retention <15% confirming the diagnosis, and bile acid sequestrants (cholestyramine or colesevelam) are first-line treatment, with response rates of 96% in severe cases (<5% retention). 1, 2

Clinical Context and High-Risk Populations

Before testing for bile acid diarrhea (BAD), exclude other common causes of chronic diarrhea:

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

Strongly consider BAD testing in these high-risk populations:

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

BAD is more common than initially perceived, with an estimated population prevalence of approximately 1%, and represents a third of patients labeled with diarrhea-predominant IBS. 1

Diagnostic Testing

Preferred Test: SeHCAT

SeHCAT (selenium-75-labeled tauroselcholic acid) is the gold standard diagnostic test with the highest diagnostic yield among all biomarkers for BAD. 1, 2

Interpretation of SeHCAT 7-day retention values:

• <5% = severe BAD (96% response to bile acid sequestrants) 1, 2
• 5-10% = moderate BAD (80% response to treatment) 1, 2
• 10-15% = mild BAD (70% response to treatment) 1, 2
• >15% = normal 1

The British Society of Gastroenterology notes that a systematic review and meta-analysis of 36 studies and 5,028 patients concluded that SeHCAT had the highest diagnostic yield, with 25% of patients previously diagnosed with functional diarrhea actually having primary BAD. 1

Alternative Tests When SeHCAT Unavailable

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

• Levels >47.1 ng/mL indicate BAD 1
• Negative predictive value of 95% (positive predictive value 74%) compared with SeHCAT 1
• Requires fasting sample; undergoes diurnal and postprandial variation 1
• False positives occur in liver disease 1
• Recent research shows C4 <15 ng/mL has 85% negative predictive value; C4 >48 ng/mL has 82% positive predictive value 3

Fecal bile acid measurement:

• Values >2,300 μmol/48 hours indicate BAD 1
• Requires 48-hour stool collection 1
• Not yet commercially available in the UK but available in North America 1

Serum FGF-19 (fibroblast growth factor 19):

• Less reliable than C4 or SeHCAT 1
• Requires fasting sample with diurnal variation 1

Critical Diagnostic Pitfall

The British Society of Gastroenterology strongly recommends AGAINST using empiric bile acid sequestrant trials instead of making a positive diagnosis. 1, 2

This is a crucial point because:

• 44% of confirmed BAD patients fail cholestyramine alone, with half responding to colesevelam 1, 2
• Lack of response to cholestyramine does NOT exclude BAD 1, 2
• Empiric trials lead to diagnostic uncertainty and repeat unnecessary testing 2
• Therapeutic trials are not recommended as they do not constitute proper diagnosis 1

The Canadian Association of Gastroenterology emphasizes that the lack of a universally agreed-upon reference standard for BAD has led to important uncertainties, but response to bile acid sequestrant therapy (BAST) provides the best available, though imperfect, reference standard. 1

Treatment

First-Line: Bile Acid Sequestrants

Cholestyramine:

• First-line treatment for BAD 4, 5
• Anion exchange resin that binds bile acids in the intestine, forming insoluble complexes excreted in feces 6, 5
• Often poorly tolerated due to unpleasant taste and side effects 4
• Dose must be titrated carefully in each patient 7

Colesevelam:

• Second-generation sequestrant, generally better tolerated than cholestyramine 4
• Available in tablets 4
• Start with two tablets twice daily, titrated according to effect 4
• Effective alternative for patients who fail cholestyramine 1, 4
• Demonstrated superiority over placebo in inducing remission in SeHCAT-diagnosed BAD 4

Administration guidelines:

• Take with meals, not on empty stomach 4
• Other medications should be taken at least 1 hour before or 4-6 hours after sequestrants to avoid drug interactions 4

Important Treatment Considerations

Monitor for fat-soluble vitamin deficiencies:

• Prolonged use can interfere with absorption of vitamins A, D, E, and K 4
• Vitamin D deficiency occurs in 20% of patients using bile acid sequestrants 4
• Supplementation may be required 4

Long-term outcomes:

• In primary BAD, 85% of patients need continued medical treatment (median follow-up 8.3 years) 8
• After discontinuation, approximately 41.6% experience symptom recurrence 4
• 14.6% report spontaneous remission after median 2.9 years 8

When Sequestrants Fail

For patients not responding to treatment, seek additional causes:

• Bacterial overgrowth 1
• Pancreatic insufficiency 1
• Microscopic colitis 1

This is important even if SeHCAT testing has been abnormal, as multiple conditions can coexist. 1

Emerging Therapies

Recent research suggests future treatment options may include:

• Farnesoid X receptor agonists 9
• GLP-1 agonists 7, 9

Special Populations

Post-cholecystectomy:

• 82% still need treatment after median 7.7 years 8
• Most respond to cholestyramine 8

Pelvic cancer with chemoradiotherapy:

• 50% have BAD, an under-recognized complication 1

Post-infectious diarrhea:

• BAD has been reported as a complication 1