What are the management options for biliary (bile acid) diarrhea?

Diagnostics and Management of Biliary Diarrhoea

Diagnostic Approach

For patients with chronic diarrhea, bile acid diarrhea (BAD) should be actively considered when risk factors are present, particularly terminal ileal resection, cholecystectomy, or abdominal radiotherapy, and diagnostic testing with SeHCAT (where available) or serum 7α-hydroxy-4-cholesten-3-one (C4) is preferred over empiric treatment. 1

Risk Factor Assessment

• Identify high-risk patients including those with terminal ileal resection, cholecystectomy, abdominal radiotherapy, Crohn's disease without active inflammation, irritable bowel syndrome with diarrhea (IBS-D), or functional diarrhea 1, 2
• Post-cholecystectomy diarrhea has particularly high rates of BAD, with 88% response to cholestyramine in confirmed cases 3
• Approximately 30% of patients diagnosed with IBS-D or functional diarrhea have underlying BAD 4

Diagnostic Testing Strategy

• SeHCAT testing is the preferred diagnostic test when available, with retention <15% indicating BAD 1, 2
• Serum C4 (7α-hydroxy-4-cholesten-3-one) serves as an alternative where SeHCAT is unavailable 1, 2
• Testing is suggested over empiric bile acid sequestrant therapy, as it predicts treatment response and avoids unnecessary medication trials 1, 3
• The Canadian Association of Gastroenterology recommends testing even in patients with IBS-D, functional diarrhea, and Crohn's disease without inflammation 1

Clinical Presentation

• Patients typically present with chronic, watery diarrhea without blood or mucus 5
• The severity of bile acid loss determines presentation: mild to moderate BAD causes watery diarrhea alone, while severe BAD causes both diarrhea and steatorrhea 5

Treatment Algorithm

First-Line Therapy

Cholestyramine is recommended as initial therapy for confirmed or suspected BAD, starting at 4 g once or twice daily with meals, then titrating to 2-12 g/day based on symptom response. 1, 3

• Cholestyramine achieves clinical response in approximately 70% of patients overall 1, 6
• Response rates vary by SeHCAT retention: 67% with retention <5%, 73% with retention <8-11.7%, and 59% with retention <15% 1
• The medication works by binding bile acids in the intestine to form an insoluble complex that is excreted in feces, preventing colonic secretion 7

Dosing and Administration

• Start with 4 g once or twice daily with meals to minimize gastrointestinal side effects 3
• Titrate upward based on symptom response, with typical effective doses ranging from 2-12 g/day 3
• Administer other medications either 1 hour before or 4-6 hours after cholestyramine to avoid binding interactions 3

Alternative Bile Acid Sequestrants

• When cholestyramine is not tolerated, consider colesevelam as an alternative with potentially better tolerability 1, 6
• Colesevelam has fewer drug interactions and may be better tolerated than cholestyramine 8
• Colestipol is another alternative, though less studied than cholestyramine 6
• Hydroxypropyl cellulose may have some efficacy, though evidence is limited 1, 3

Management of Treatment Failures

• For patients with extensive ileal Crohn's disease or resection, bile acid sequestrants are suggested against, as these patients may have severe BAD with steatorrhea that worsens with sequestrant therapy 1, 5
• In severe BAD with steatorrhea, use a low-fat diet supplemented with medium-chain triglycerides instead of bile acid sequestrants 5
• If bile acid sequestrants are not tolerated, consider alternative antidiarrheal agents such as loperamide 3

Addressing Comorbid Conditions

• Before or concurrent with BAD treatment, address other remediable causes of gastrointestinal symptoms, with therapy order guided by severity of each condition 1
• In patients with microscopic colitis and BAD, 86% benefit from bile acid sequestrants, but those without BAD do not improve and may require corticosteroids, antibiotics, or immunosuppressive therapies 1
• Patients with small intestinal bacterial overgrowth (SIBO) require antibiotic therapy as the primary treatment, though some may also benefit from bile acid sequestrants 1

Long-Term Management

Maintenance Therapy

• Maintain treatment at the lowest effective dose to minimize side effects and cost 1, 9
• Consider a trial of intermittent, on-demand administration rather than continuous therapy 1
• Approximately 39-94% of patients experience recurrent diarrhea when cholestyramine is withdrawn, depending on underlying cause and severity 3

Monitoring for Adverse Effects

• Monitor for fat-soluble vitamin deficiencies (vitamins A, D, E, K), as prolonged cholestyramine use causes malabsorption in 20% of patients 3
• Check serum bicarbonate and chloride levels to detect hyperchloremic metabolic acidosis, particularly in patients with renal impairment or volume depletion 3
• Review concurrent medications regularly, as bile acid sequestrants reduce bioavailability of many co-administered drugs 6

Management of Persistent Symptoms

• If symptoms persist despite bile acid sequestrant therapy, conduct medication review and reinvestigation for alternative diagnoses 1, 9
• Consider colonoscopy with biopsies if not previously performed, as microscopic colitis and other conditions may coexist 1, 2
• Reassess for other causes of chronic diarrhea including celiac disease, inflammatory bowel disease, and medication-induced diarrhea 2

Common Pitfalls to Avoid

• Do not assume functional diarrhea based on Rome IV criteria alone, as these have only 52-74% specificity and do not reliably exclude BAD, microscopic colitis, or IBD 2
• Do not overlook BAD in patients with prior cholecystectomy or ileal resection, as this is a frequently missed diagnosis 2
• Do not use bile acid sequestrants in patients with severe BAD and steatorrhea, as this worsens fat malabsorption; instead use low-fat diet with medium-chain triglycerides 5
• Do not administer other medications concurrently with cholestyramine without appropriate timing separation, as binding reduces their bioavailability 3, 6
• Do not neglect vitamin supplementation in patients on long-term bile acid sequestrant therapy, particularly vitamin D 3

Emerging Therapies

• GLP-1 receptor agonists such as liraglutide show effectiveness for BAD, though mechanisms and class effects require further validation 8
• FXR agonists including obeticholic acid show promise in proof-of-concept studies, though require further validation before routine use 6, 8