When to give or withhold ursodeoxycholic acid (UDCA) to patients?

When to Give and Not Give Ursodeoxycholic Acid (UDCA)

Give UDCA in Primary Biliary Cholangitis (PBC)

UDCA at 13-15 mg/kg/day is the established first-line treatment for primary biliary cholangitis and should be given lifelong. 1, 2

Dosing and Administration for PBC

• Standard dose: 13-15 mg/kg/day divided in 2-3 doses 1, 3
• This dose provides optimal biochemical improvement and bile acid enrichment without additional benefit from higher doses 3, 4
• Lower doses (5-7 mg/kg/day) are inadequate and should not be used 3
• Higher doses (23-25 mg/kg/day) offer no additional benefit over standard dosing 3

Expected Benefits in PBC

• Significantly reduces serum bilirubin, alkaline phosphatase, gamma-glutamyl transferase, and cholesterol levels 1, 5
• Delays histological progression when started at early disease stages 1, 2
• Reduces likelihood of liver transplantation or death in patients with moderate to severe disease 1, 2
• Continue UDCA lifelong after liver transplantation in PBC patients to prevent disease recurrence 1

Monitoring Response in PBC

• Assess biochemical response after 1 year of therapy to identify patients at risk for progressive disease 2
• AMA-positive individuals with normal liver tests should undergo annual reassessment of cholestasis markers 1, 2
• UDCA does not significantly improve symptoms like pruritus or fatigue, so symptom response should not guide treatment decisions 1

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Do NOT Give UDCA in Primary Sclerosing Cholangitis (PSC)

UDCA is not recommended for routine treatment of PSC and may be harmful at high doses. 1, 2

Evidence Against UDCA in PSC

• Multiple guidelines strongly recommend against UDCA use in adult PSC patients 1, 2
• Standard doses (13-15 mg/kg/day) improve liver biochemistry but do not improve clinical outcomes including death, transplantation, or histological progression 1
• High-dose UDCA (28-30 mg/kg/day) is associated with increased serious adverse events, higher rates of death, liver transplantation, and variceal development 1
• A large multicenter trial of high-dose UDCA was terminated early due to harm in the treatment group 1

Exception: PSC/AIH Overlap Syndrome

• In patients with PSC and autoimmune hepatitis overlap features, use corticosteroids and immunosuppressive agents instead of UDCA 1
• These patients are more likely to respond to immunosuppressive treatment 1

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Do NOT Give UDCA in Hepatic Steatosis (NAFLD/NASH)

UDCA is explicitly not recommended for treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. 6

Evidence Against UDCA in Steatosis

• The American Association for the Study of Liver Diseases states UDCA should not be used for NAFLD/NASH (Strength 1, Quality B) 6
• A large multicenter randomized controlled trial demonstrated no histological benefit over placebo in NASH patients 6
• While UDCA may improve liver biochemistry, this does not translate to improved clinical outcomes 6

Alternative Treatments for NASH

• For non-diabetic adults with biopsy-proven NASH: Vitamin E (α-tocopherol) 800 IU/day is first-line pharmacotherapy 6
• Lifestyle modifications with weight loss through diet and exercise remain the cornerstone of management 6

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Give UDCA for Gallstone Dissolution and Prevention

Gallstone Dissolution

• Indicated for radiolucent, non-calcified gallbladder stones <20 mm in patients who are poor surgical candidates 7
• Dose: 8-10 mg/kg/day divided in 2-3 doses 7
• Monitor with ultrasound at 6-month intervals during the first year 7
• If partial dissolution is not seen by 12 months, likelihood of success is greatly reduced 7
• Safety beyond 24 months is not established 7

Gallstone Prevention During Rapid Weight Loss

• Indicated for obese patients experiencing rapid weight loss 7
• Dose: 600 mg/day (300 mg twice daily) 7

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Important Safety Considerations

Contraindications and Warnings

• Hold UDCA if patient develops obstructive gastrointestinal symptoms 7
• Rare cases of enteroliths (bezoars) requiring surgical intervention have occurred in patients with intestinal stenosis or stasis (e.g., Crohn's disease, surgical enteroanastomoses) 7

Pregnancy and Breastfeeding

• UDCA is considered safe during pregnancy and breastfeeding, particularly for women with PBC who require continued treatment 2
• For intrahepatic cholestasis of pregnancy, initial dose is 10-15 mg/kg/day divided in 2-3 doses 2

Common Pitfalls to Avoid

• Do not use high-dose UDCA (>25 mg/kg/day) in any condition - associated with harm in PSC 1
• Do not prescribe UDCA for PSC based solely on biochemical improvement - this does not correlate with clinical benefit 1
• Do not continue UDCA in PSC patients already on high doses (28-30 mg/kg/day) - consider discontinuation due to potential harm 1
• Do not expect symptom improvement in PBC - UDCA primarily affects biochemistry and disease progression, not pruritus or fatigue 1