Diurnal variation in cholesterol metastability of hepatic bile and its acute modulation with ursodeoxycholic acid in humans.

We studied the alteration of cholesterol metastability of hepatic bile caused by diurnal variations in hepatic biliary lipid excretions and acutely induced changes following ursodeoxycholic acid (UCDA) administration. Hepatic bile was collected at 6-h intervals for 24 h from 6 patients with an indwelling choledochal drainage before and after UDCA administration. A basal diurnal variation showed the highest cholesterol saturation index (p < 0.05) and cholesterol distribution in vesicles (p < 0.01) and the shortest nucleation time (p < 0.05) in the early morning. After the ingestion of ursodeoxycholic acid for 1 day, early morning biliary cholesterol concentrations were reduced. Interestingly, significant decreases in vesicular cholesterol concentrations (1.0 +/- 0.2 to 0.1 +/- 0.04 mM, p < 0.01) and in the vesicular cholesterol/phospholipid ratio (1.6 +/- 0.1 to 0.7 +/- 0.1, p < 0.05) were associated with prolongation of the nucleation time (11.5 +/- 1.2 to 18.7 +/- 1.5 days, p < 0.01). Biliary protein had no diurnal variations and did not decrease significantly with UCDA. These results indicate that during a day the early morning hepatic bile is the most unstable and that UCDA acutely enhances hepatic biliary metastability mainly by decreasing the rate of vesicular cholesterol saturation.