Bile saturated with cholesterol is a prerequesite for formation of cholesterol gallstones; saturation probably results from increased biliary cholesterol and possibly decreased biliary bile acids. Saturated bile alone, however, is not sufficient for gallstones to form. One hypothesis is that saturated bile stimulates biliary prostanoids which increase secretion of glycoproteins into bile. The glycoproteins promote precipitation of crystals of cholesterol, the formation of sludge, and, ultimately, the formation of gallstones. Another hypothesis is that saturated bile impairs emptying of the gallbladder, with stasis of bile promoting precipitation of cholesterol. Obese patients are predisposed to cholesterol-saturated bile and have a two to three-fold greater prevalence of cholesterol gallstones than non-obese patients. Weight loss may promote the formation of gallstones by increasing cholesterol saturation or enhancing cholesterol precipitation. This study is a prospective, double-blind, randomized, controlled trial in obese patients enrolled in a program for reduction of weight.
The aim of the study is to determine the effect of loss of weight on composition of biliary lipids, glycoproteins, and prostanoids; the saturation of biliary cholesterol; the synthesis of cholesterol; emptying of the gallbladder; and the formation of biliary cholesterol crystals, sludge and gallstones. The trial also will determine the effects of ursodeoxycholic acid (a bile acid which unsaturates bile) or aspirin (an inhibitor of synthesis of prostanoids) on these same parameters. Design: Forty-five obese patients will participate for four months. Prior to beginning weight reduction, patients wil undergo ultrasonography (to identify sludge and gallstones) and cholescintigraphy of the gallbladder (to measure gallbladder emptying) and duodenal drainage for analysis of bile (biliary lipids, glycoproteins, prostanoids saturation of biliary cholesterol, cholesterol crystal's and synthesis of cholesterol). Patients will receive ursodeoxycholic acid (600 mg BID), aspirin (650 mg BID) or placebo (BID) during weight reduction. Ultrasonography, cholescintigraphy, and duodenal drainage will be repeated at four weeks and ultrasonography and duodenal drainage will be repeated again at 16 weeks (earlier if the patient completes the weight reduction program prior to 16 weeks).
| Yang, H; Petersen, G M; Roth, M P et al. (1992) Risk factors for gallstone formation during rapid loss of weight. Dig Dis Sci 37:912-8 |
