Effect of ursodeoxycholic acid on the masses of biliary lipids and alkaline phosphatase within the gallbladder in chronic cholestatic liver disease

Objectives: To verify whether the improvement of the cholestatic indices caused by ursodeoxycholic acid administered for chronic intrahepatic cholestasis is due to a dilution or a removal of the hydrophobic bile acids in the bile. To assess the effect of ursodeoxycholic acid on the masses in the gallbladder of other biliary lipids and alkaline phosphatase. Design: Open prospective study. Methods: Measurement of the masses of total bile acids, bile acid conjugates, cholesterol, phospholipid and alkaline phosphatase within the gallbladder in the fasting state before and after 4-6 weeks of therapy with 600 mg per day oral ursodeoxycholic acid in eight patients with chronic cholestatic liver disease. Results: Ursodeoxycholic acid caused a significant increase in the bile acid mass (from 1976 ± 593 to 4562 ± 1474 μmol; P <0.02), that was entirely due to an increased mass of its conjugates (from 35 ± 20 to 1623 ± 768 μmol; P <0.05), whereas the masses of all the other bile acid conjugates were not modified during therapy. In all eight patients, serum alkaline phosphatase concentration decreased during ursodeoxycholic acid therapy, whereas the alkaline phosphatase mass within the gallbladder increased, from 16 ± 3 IU to 35 ± 9 IU (P <0.02). There was no change in the cholesterol and phospholipid masses. Conclusion: Our results indicate that the mechanism of action of ursodeoxycholic acid in chronic intrahepatic cholestasis is not mediated via a reduction of the hydrophobic bile acids handled by the liver, though these are diluted out by ursodeoxycholic acid. The finding of an increased mass of alkaline phosphatase in the gallbladder is probably due to the well known choleretic effect of ursodeoxycholic acid.