Diurnal Variation in Biliary Lipid Composition: Possible Role in Cholesterol Gallstone Formation

Biliary lipid composition was determined on gallbladder bile and on hepatic bile during the diurnal cycle of feeding and fasting in American Indians with and without gallstones and in Caucasian women without gallstones. Fasting hepatic bile was consistently more lithogenic than gallbladder bile or hepatic bile obtained during feeding. Although lithogenicity was greater in Indians, even Caucasian women regularly produce more highly lithogenic bile during the fasting period, apparently because of an uncoupling of cholesterol and bile acid secretion. Although bile acids were sequestered in the gallbladder during late fasting, cholesterol secretion continued somewhat independently of bile acids, thus enhancing lithogenicity. This effect was more pronounced in Indian women, who have reduced pools of bile acids and increased cholesterol secretion. An increasing lithogenicity of hepatic bile throughout fasting might contribute to cholesterol gallstone formation if mixing in the gallbladder is incomplete so that levels of lithogenic bile become segregated. THE majority of patients with cholesterol gallstones have an abnormal bile lipid composition characterized by an excessive amount of cholesterol in relation to the solubilizing lipids — bile acids and phospholipids.^1,2 This abnormal bile has been designated “lithogenic bile.” Several lines of evidence support the concept that this abnormality results from alteration in hepatic secretion of biliary lipids³ that is associated with a decrease in the bile acid pool size^{4 5 6 7 8} and an increased hepatic secretion of cholesterol.^{8 9} However, in 30 to 40 per cent of patients with gallstones gallbladder bile is not lithogenic by the usual criteria on a single.