What is the effect of ursodeoxycholic acid (UDCA) on gallstones?

Effect of Ursodeoxycholic Acid on Gallstones

Ursodeoxycholic acid (UDCA) at 8-10 mg/kg/day effectively dissolves cholesterol gallstones in approximately 30% of unselected patients with uncalcified stones <20 mm treated for up to 2 years, with dissolution rates reaching 81% for stones ≤5 mm in diameter. 1

Mechanism of Gallstone Dissolution

UDCA works through multiple mechanisms to dissolve cholesterol gallstones:

• Suppresses hepatic cholesterol synthesis and secretion while inhibiting intestinal cholesterol absorption 1
• Solubilizes cholesterol through two pathways: incorporation into micelles and dispersion as liquid crystals in aqueous media 1
• Converts bile from cholesterol-precipitating to cholesterol-solubilizing, creating an environment conducive to stone dissolution 1
• Prolongs cholesterol nucleation time approximately 5-fold (from 2.3 to 12.0 days) while decreasing cholesterol saturation index 2

Optimal Dosing and Patient Selection

Dosing strategy:

• Standard dissolution dose: 8-10 mg/kg/day appears most effective based on 868 patients across 8 clinical trials 1
• Treatment duration typically requires up to 2 years for complete dissolution 1
• Steady-state bile concentrations achieved in approximately 3 weeks 1

Ideal candidates for UDCA therapy:

• Radiolucent (uncalcified) gallstones <20 mm in maximal diameter 1
• Floating or floatable stones (high cholesterol content) achieve up to 50% dissolution rates 1
• Smaller stones respond better: 81% complete dissolution for stones ≤5 mm versus 30% for stones up to 20 mm 1
• Functioning gallbladder required (though nonvisualization on initial cholecystogram is not a contraindication) 1

Predictors of Treatment Failure

Discontinue UDCA if:

• Calcified gallstones present before or develop during treatment 1
• Gallbladder nonvisualization develops during therapy (predicts failure) 1
• Stones >20 mm in diameter (rarely dissolve) 1

Patient factors that do NOT affect dissolution: Age, sex, weight, obesity degree, and serum cholesterol levels are unrelated to dissolution success 1

Comparative Efficacy

UDCA demonstrates superior efficacy compared to chenodeoxycholic acid (CDCA):

• UDCA significantly more effective than CDCA at 3 and 6 months of treatment 3
• 74% of total dissolutions with UDCA occur within first 6 months versus 42% with CDCA 3
• UDCA equally effective at high and low doses on both small and large stones, while CDCA requires higher doses for efficacy 3
• UDCA has superior safety profile: no diarrhea or transaminase elevation, unlike CDCA 3

Prevention of Stone Recurrence

Low-dose UDCA (250 mg/day at bedtime) may prevent post-dissolution recurrence by:

• Decreasing cholesterol saturation index (0.94 vs. 1.43 in controls) 2
• Prolonging cholesterol nucleation time 5-fold 2
• Preliminary data suggests reduced recurrence rates in younger patients 2

Important Caveats and Limitations

Treatment failures occur in specific populations:

• Cystic fibrosis patients: UDCA ineffective even at 15-20 mg/kg/day because stones are not primarily cholesterol-based 4
• Non-cholesterol stones: UDCA only dissolves cholesterol gallstones, not pigment or mixed stones 4

Rare paradoxical complication:

• UDCA can form stones itself via unknown mechanism, causing recurrent cholangitis from UDCA stones in the common bile duct 5
• Withdrawal of UDCA highly effective if recurrent cholangitis occurs shortly after starting therapy 5
• Rethink UDCA indication if cholangitis from CBD stones recurs frequently over short periods 5

Post-treatment considerations:

• Bile acid concentration falls exponentially after stopping UDCA, declining to 5-10% of steady-state in approximately 1 week 1
• High stone recurrence rate remains a drawback of non-surgical therapy 2

Clinical Bottom Line

UDCA represents the medical treatment of choice for dissolving small (<20 mm), radiolucent, cholesterol gallstones in patients with functioning gallbladders, achieving best results with stones ≤5 mm diameter. However, only 30% of unselected patients achieve complete dissolution, and treatment requires prolonged therapy (up to 2 years). Surgical cholecystectomy remains definitive treatment for most symptomatic gallstone disease given UDCA's limited efficacy and high recurrence rates after dissolution.