Effect of chenodeoxycholate and ursodeoxycholate on nucleation time in human gallbladder bile.

Area of Science:

• Hepatology
• Gastroenterology
• Biliary Physiology

Background:

• Cholesterol gallstones form when bile becomes supersaturated with cholesterol.
• Bile acid therapy aims to dissolve existing gallstones and prevent new ones.
• Understanding the effects of specific bile acids on nucleation and lipid composition is crucial for treatment efficacy.

Purpose of the Study:

• To investigate the impact of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) on biliary nucleation time and lipid composition in cholesterol gallstone patients.
• To compare the mechanisms by which CDCA and UDCA affect biliary cholesterol saturation and vesicular lipid dynamics.

Main Methods:

• Gallbladder bile was collected from 33 cholesterol gallstone patients pretreated with CDCA or UDCA, and from 9 controls.
• Nucleation time, biliary lipid concentration, and vesicular lipid composition were analyzed.
• Cholesterol saturation index was calculated to assess bile's capacity to dissolve cholesterol.

Main Results:

• Both CDCA and UDCA significantly prolonged nucleation time compared to untreated patients.
• Both bile acids reduced cholesterol and phospholipid concentrations in the vesicular phase.
• UDCA decreased the cholesterol saturation index more effectively than CDCA at the doses studied.

Conclusions:

• UDCA prolongs nucleation time primarily by reducing the cholesterol saturation index.
• CDCA prolongs nucleation time through a dual mechanism: lowering cholesterol saturation and shifting cholesterol from vesicles to micelles.
• These findings highlight differential effects of UDCA and CDCA on biliary physiology relevant to gallstone formation and dissolution.