Cholesterol Gallstone Formation
Cholesterol supersaturates bile, then crystallizes into a stone.
- 80%: Cholesterol stone share (of all gallstones)
- 2–30 mm: Typical stone size range (variable diameter)
- <15 mm: Ideal UDCA candidate size (radiolucent stones)
- 10–15%: US adult prevalence (have gallstones)
Cholesterol supersaturation
Bile carries more cholesterol than it can dissolve.
Nucleation and crystal growth
Cholesterol monohydrate crystals aggregate into a solid stone.
Radiolucent vs radiopaque stones
Pure cholesterol stones lack calcium and stay radiolucent.
Only radiolucent, cholesterol-rich stones respond well to UDCA.
Ursodeoxycholic Acid Treatment Begins
Oral UDCA gradually replaces toxic bile acids in circulation.
- 8–10: Typical daily dose (mg/kg per day)
- ~90%: Ileal bioavailability (absorbed efficiently)
- 2–4 wks: Onset of bile pool shift (to change composition)
- Ursodiol: Common brand name (generic UDCA)
Mechanism of action
UDCA displaces cholesterol-rich bile acids from the circulating pool.
Hepatic cholesterol secretion
UDCA reduces how much cholesterol the liver secretes.
Tolerability profile
UDCA is well tolerated, with only mild side effects.
Therapy typically continues for six to twenty-four months.
Bile Cholesterol Desaturation
The cholesterol saturation index of bile falls below one.
- >1.0: Saturation index before (supersaturated bile)
- <0.7: Saturation index after (undersaturated bile)
- +40%: Micelle carrying capacity (more cholesterol held)
- 1–3 mo: Time to desaturate bile (typical range)
Micelle and vesicle changes
UDCA reshapes bile carriers so they hold more cholesterol.
The driver of dissolution
Undersaturated bile pulls cholesterol back out of the stone.
Monitoring desaturation
Ultrasound tracks stone size every few months.
Desaturated bile is the prerequisite for any dissolution.
Gradual Layer-by-Layer Dissolution
The stone surface shrinks slowly, month after month.
- ~1 mm/mo: Typical dissolution rate (for small stones)
- <10 mm: Best candidate stone size (fastest full dissolution)
- 70–90%: Success rate, small stones (complete dissolution)
- <30%: Success rate, large stones (often incomplete)
Surface-limited kinetics
Only the exposed outer layer dissolves each cycle.
Size dependence
Larger stones need proportionally much longer therapy.
Recurrence risk
Stones can reform if therapy stops too early.
Small stones under ten millimeters dissolve fastest and best.
Complete or Partial Dissolution Outcome
Small stones vanish; large stones often remain, unchanged.
- 6–24 mo: Complete dissolution window (for small stones)
- 30–50%: Recurrence within 5 years (after stopping therapy)
- >20 mm: Non-response threshold (rarely fully dissolves)
- Surgery: Alternative if therapy fails (cholecystectomy option)
Confirming complete dissolution
Repeat ultrasound confirms the stone has disappeared.
Partial response management
Persisting stones may continue therapy or change approach.
Long-term follow-up
Recurrence monitoring continues after successful dissolution.
Even dissolved stones can recur without lasting diet change.