Ursodeoxycholic Acid for Gallstone Dissolution
For dissolving small, uncalcified cholesterol gallstones, ursodeoxycholic acid (UDCA) should be administered at 8-10 mg/kg/day in 2-3 divided doses, with bedtime dosing offering enhanced efficacy at the lower end of this range. 1, 2
Patient Selection Criteria
The success of UDCA therapy depends critically on appropriate patient selection:
- Optimal candidates: Patients with radiolucent (non-calcified), floating cholesterol stones less than 5-10 mm in diameter achieve dissolution rates up to 80-81% 1, 3
- Acceptable candidates: Stones up to 20 mm in diameter can be treated, though success rates decline significantly with increasing stone size 1
- Poor candidates: Patients with calcified gallstones, stones >20 mm diameter, or gallbladder nonvisualization rarely achieve dissolution and should not be treated 1
- Essential requirement: A functioning gallbladder demonstrated by oral cholecystogram is necessary for therapy 1
Dosing Regimen
Standard dosing: 8-10 mg/kg/day divided into 2-3 doses 1, 3, 4
Optimized regimen: 8.4 mg/kg/day administered as a single bedtime dose reduces the minimum effective dose while maintaining efficacy 2. This bedtime administration strategy achieves superior bile desaturation compared to mealtime dosing at equivalent or lower doses 2.
The FDA-approved dosing range is 8-10 mg/kg/day given in 2 or 3 divided doses 1.
Treatment Duration and Monitoring
- Initial monitoring: Obtain ultrasound images at 6-month intervals during the first year to assess stone response 1
- Expected timeline: Most patients achieving complete dissolution show partial dissolution within 6 months, with 74% of complete dissolutions occurring within the first 6 months 5
- Continuation criteria: If partial stone dissolution is not evident by 12 months, the likelihood of success is greatly reduced and therapy should be reconsidered 1
- Confirmation: Once stones appear dissolved, continue UDCA and confirm dissolution on repeat ultrasound within 1-3 months 1
Expected Outcomes
Overall success rates:
- Unselected patients with radiolucent stones <20 mm: approximately 30% complete dissolution at 2 years 1
- Selected patients with floating stones <10-15 mm: up to 80% complete dissolution 3
- Stones up to 5 mm diameter: 81% complete dissolution 1
Comparative efficacy: UDCA at 8-10 mg/kg/day achieves results equivalent to chenodeoxycholic acid at 15 mg/kg/day, but with significantly better tolerability 3, 5. UDCA was significantly more effective than chenodeoxycholic acid at 3 and 6 months of treatment 5.
Safety Profile
UDCA demonstrates remarkable tolerability compared to alternative bile acid therapy:
- Diarrhea: Occurs in only a very small proportion of patients, unlike chenodeoxycholic acid which commonly causes this side effect 3, 5
- Liver function: Laboratory studies including liver function tests are not adversely affected 4
- Lithocholic acid: Biliary lithocholic acid concentrations do not increase during therapy 4
- Symptom relief: Most biliary symptoms disappear within 3 months of initiating therapy 4
Critical Pitfalls
Gallbladder nonvisualization during treatment: If the gallbladder becomes nonvisualizing after initiating UDCA therapy, this predicts failure of complete stone dissolution and therapy should be discontinued 1. However, a nonvisualizing gallbladder prior to treatment initiation is not a contraindication 1.
Stone recurrence: Recurrence occurs in 30% of patients within 2 years and up to 50% within 5 years after complete dissolution 1. Serial ultrasonographic monitoring is essential to detect recurrence, and radiolucency should be re-established before instituting another course of UDCA 1.
Calcification development: Patients who develop stone calcification during treatment rarely achieve dissolution and should discontinue therapy 1.