Effect of Chenodeoxycholate and Ursodeoxycholate on Nucleation Time in Human Gallbladder Bile

The effects of treatment with chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) on nucleation time, biliary lipid concentration, and vesicular lipid composition were studied. Gallbladder bile was collected at the time of surgery from 33 cholesterol gallstone patients who were divided into three groups: 16 untreated, 9 pretreated with CDCA (400 mg/day), and 8 pretreated with UDCA (600 mg/day) for 1-3 weeks before surgery. Control bile samples were also collected from nine patients without cholelithiasis. Nucleation time was prolonged significantly in both CDCA- and UDCA-treated groups [12.6 +/- 8.5 (SD) and 21.0 +/- 0 days, respectively] compared with the untreated gallstone group (3.3 +/- 3.2 days). Both treatments significantly decreased the proportion and concentration of both cholesterol and phospholipids present in the vesicular phase. Treatment with UDCA decreased the cholesterol saturation index more than did CDCA at the dose used in this study. In the CDCA-treated group, patients without much change in cholesterol saturation index (greater than 1.0) showed a prolongation of the nucleation time with a significant decrease in vesicular cholesterol concentration, indicating a shift of cholesterol from vesicles to micelles. UDCA-treated patients and CDCA-treated patients with decreased cholesterol saturation index (less than 1.0) showed a greater effect. The authors conclude that UDCA prolongs the nucleation time mainly by decreasing the cholesterol saturation index, whereas CDCA does so by the dual effect of lowering the cholesterol saturation index and shifting cholesterol from vesicles to micelles.