Lipid solubilization in human gallbladder versus hepatic biles

Background/Aims: Cholesterol crystallizes more rapidly in gallbladder than in hepatic biles, supposedly due to formation of cholesterol-supersaturated vesicles in concentrated gallbladder biles because of preferential micellization of phospholipids compared to cholesterol. We therefore aimed to compare lipid solubilization in hepatic and gallbladder biles. Methods: Mixed micellar and vesicular phases were separated from hepatic and associated gallbladder biles of seven cholesterol gallstone patients by using state-of-the-art gel filtration with bile salts at intermixed micellar/intervesicular compositions and concentrations in the eluant. Results: Vesicles were found in 6 out of 7 hepatic biles, but only in 2 of the corresponding gallbladder biles. Both percentage (7.8±5.1 vs. 36.3±7.6%; p=0.01) and amount (0.9±0.2 vs. 1.7±0.3 mM; p=0.06) of vesicular cholesterol were lower in gallbladder biles. Similar results were found for vesicular phospholipids (1.3±0.8 vs. 11.6±6.0%; p=0.05; and 0.3±0.1 vs. 1.1±0.5 mM; p=0.07). The vesicular cholesterol/phospholipid ratio was 1.7±0.5 in hepatic bile but 4.3 and 1.8 in the 2 gallbladder biles which contained vesicles. Mixed micelles in gallbladder biles had a higher cholesterol saturation index than mixed micelles in hepatic biles (1.43±0.11 vs. 1.15±0.07; p=0.02). Conclusions: Concentration of bile in the gallbladder leads to decreased vesicular lipid contents. The finding of supersaturated mixed micelles in the absence of vesicles in a significant number of patients points to the possibility of non-vesicular modes of crystallization.