Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones

The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation and/or nucleation time of cholesterol. Ten patients with cholesterol gallstones and functioning gallbladder received 250 mg ursodeoxycholic acid/day at bedtime 6–10 days prior to cholecystectomy. Eleven patients with cholesterol gallstones without treatment served as controls. Cholesterol crystals were present in the gallbladder bile of 7 out of the 10 patients receiving ursodeoxycholic acid and in all control biles. Ursodeoxycholic acid treatment significantly (P < 0.02) decreased the cholesterol saturation index (mean ± S.E.: 0.94 ± 0.05 vs. 1.43 ± 0.18) and led to an approximately 5-fold prolongation (P < 0.005) of the cholesterol nucleation time (mean ± S.E.: 12.0 ± 2,4 vs. 2.3 ± 0.7 days). We conclude that lowdose ursodeoxycholic acid might be effective in the prevention of post-dissolution gallstone recurrence by both decreasing cholesterol saturation and prolonging cholesterol nucieation tim

Lipid composition and cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones under choleretic treatment with febuprol

The effect of a new potent choleretic drug (Febuprol) on lipid composition and cholesterol nucleation time in gallbladder bile was studied in 8 patients with cholesterol gallstones. Nine untreated patients with cholesterol cholecystolithiasis and functioning gallbladder served as controls. Under Febuprol treatment (3 X 100 mg for 6-10 days) mean concentrations of total bile acids (125.4 vs. 59.5 mmol/l), phospholipids (46.1 vs. 25.6 mmol/l) and total lipids (10.4 vs. 5.9 g/dl) were significantly higher (p less than 0.01) than in controls. No significant difference between both groups was calculated for the mean values of cholesterol (17.8 vs. 13.3 mmol/l), cholesterol saturation index (1.5 vs. 2.1) and cholesterol nucleation time (2.1 vs. 2.6 days). Our findings are compatible with a choleretic effect of Febuprol but no alteration of the rapid cholesterol crystallisation in gallbladder bile of patients with cholesterol gallstones was found

Cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined. The cholesterol nucleation time was significantly (p 4 days) nucleation time. However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 ± 0.65 vs. 1.54 ± 0.59, mean ± S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones