Abstract
Ursodeoxycholic acid has been proposed for the treatment of primary biliary cirrhosis. The aim of this study was to evaluate the effect of ursodeoxycholic acid administration on bile acid metabolism in patients with early-stage primary biliary cirrhosis. Biliary bile acid composition, primary bile acid pool sizes, synthesis, and fractional turnover rate were measured before and after four weeks of ursodeoxycholic acid administration (600 mg/day) in nine patients with biopsy-proven primary biliary cirrhosis (stages I-III). Molar percentages of chenodeoxycholic, cholic, and deoxycholic acids in bile were significantly decreased by ursodeoxycholic acid administration, while its biliary concentration increased to 34.2% at the end of the same four-week period. The cholic and chenodeoxycholic acid pools decreased, although not significantly, while the deoxycholic acid pool was reduced by 60% (from 0.7±0.12 to 0.29±0.07 mmol,P<0.002). Primary bile acid synthesis was slightly increased, and fractional turnover rate was significantly increased. The conversion rate of cholic to deoxycholic acid was measured and found to be significantly increased (P<0.05) after ursodeoxycholic acid administration; however, serum levels of both free and conjugated deoxycholic acid were significantly decreased (from 23.2±9.7 to 3.8±1.9 μmol/liter,P<0.001). We conclude that in patients with primary biliary cirrhosis, ursodeoxycholic acid administration replaces endogenous bile acids in the enterophepatic circulation by increasing bile acid fractional turnover rate without significant increments of their hepatic synthesis.
Similar content being viewed by others
References
Poupon R, Chrétien Y, Poupon RE, Ballet F, Calmus Y, Darnis F: Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1:834–836, 1987
Roda E, Mazzella G, Villanova N, Minutello A, Simoni P, Ronchi M, Poggi C, Festi D, Aldini R, Roda A: Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis. Dig Dis Sci 34(suppl)52s-58s, 1989
Mazzella G, Villanova N, Ronchi M, Clerici C, Minutello A, Simoni P, Bazzoli F, Barbara L, Roda E: Effect of ursodeoxycholic acid on biliary lipid metabolism in primary biliary cirrhosis.In Trends in Bile Acid Research. G Paumgarner, A Stiehl, W Gerok (eds). Kluver Academic Publishers, 1989, pp 373–379
Leuschner U, Fischer H, Kurtz W, Güldütuna S, Hübner K, Hellstern A, Gatzen M, Leuschner M: Ursodeoxycholic acid in primary biliary cirrhosis: Results of a controlled doubleblind trial. Gastroenterology 97:1268–1274, 1989
Poupon RE, Balkau D, Eschwege E, Poupon R, UDCA-PBC Study Group: A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. N Engl J Med 324:1548–1554, 1991
Grundy SM: Effect of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridemia. J Clin Invest 55:269–282, 1975
Vlahcevic ZR, Juttijudata P, Bell CC, Swell L: Bile acid metabolism in patients with cirrhosis II. Cholic and chenodeoxycholic acid metabolism. Gastroenterology 62:1174–1181, 1972
Lindstedt S: Turnover of cholic acid in man. Acta Physiol Scand 40:1–9, 1957
Dowling RH, Mack E, Small DM: Effects of controlled interruption of the enterohepatic circulation of bile salt by biliary diversion and by ileal resection on bile salt secretion, synthesis, and pool size in the rhesus monkey. J Clin Invest 49:232–242, 1970
Van Berge-Henegouwen GP, Ruben A, Brandt KH: Quantitative analysis of bile acids in serum and bile using gasliquid chromatography. Clin Chim Acta 54:249–261, 1974
Mazzella G, Bazzoli F, Festi D, Ronchi M, Aldini R, Roda A, Grigolo B, Simoni P, Villanova N, Roda E: Comparative evaluation of chenodeoxycholic acid and ursodeoxycholic acid in obese patients. Effects on biliary lipid metabolism during weight maintenance and weight reduction. Gastroenterology 101:490–496, 1991
Talalay P: Enzymatic analysis of steroid hormones. Methods Biochem Anal 8:119–143, 1960
Roda A, Girotti S, Lodi S, Preti S: Development of a sensitive enzyme immunoassay for plasma and salivary steroids. Talanta 31:895–900, 1984
Roda A, Bolelli GF: Production of a high-titer antibody to bile acids. J Steroid Biochem 13:449–454, 1980
Roda E, Bazzoli F, Morselli Labate AM, Mazzella G, Roda A, Sama C, Festi D, Aldini R, Taroni F, Barbara L: Ursodeoxycholic acid vs chenodeoxycholic acid as cholesterol disolving agents: A comparative randomized study. Hepatology 2:804–810, 1982
Erlinger S, Go AL, Husson JM, Fevery J: Franco-Belgian cooperative study of ursodeoxycholic acid in the medical dissolution of gallstones: A double-blind, randomized, doseresponse study, and comparison with chenodeoxycholic acid. Hepatology 4:308–331, 1984
Fromm H, Roat JW, Gonzalez V, Sarva RP, Farivar S: Comparative efficacy and side effects of ursodeoxycholic and chenodeoxycholic acids in dissolving gallstones. A double-blind study. Gastroenterology 85:1257–1264, 1983
Scholmerich J, Becher MS, Schmidt KH: Influence of hydroxylation and conjugation of bile salts on their membrane damaging properties-studies on isolated hepatocyte and lipid membrane vescicles. Hepatology 4:661–666, 1984
Kitani K, Ohta M, Kanai S: Tauroursodeoxycholate prevents biliary excretion of protein induced by taurocholate and taurochenodeoxycholate in the rat. Hepatology 3:810, 1983 (abstract)
Kani S, Kitani K: Glycoursodeoxycholate (GU) is as effective as tauroursodeoxycholate (TU) in preventing the taurocholate (TC)-induced cholestasis in the rat. Hepatology 3:811, 1983 (abstract)
Kroll T, Kitamura T, Miyai K, Hardison W: Tauroursodeoxycholate (TUDC) reduces ductular proliferation and portal inflammation in bile-duct-ligated hamsters. Hepatology 3:881, 1983 (abstract)
Stiehl A: Disturbances of bile acid metabolism in cholestasis. Clin Gastroenterol 6:45–67, 1977
Greim H, Trülzsch D, Czygan P, Ruduck J, Hutterer F, Schaffner F, Popper H: Mechanism of cholestasis. 6. Bile acids in human livers with or without biliary obstruction. Gastroenterology 63:846–850, 1972
Akashi Y, Miyazaki H, Yanagisawa J, Nakayama F: Bile acid metabolism in cirrhotic liver tissue-altered synthesis and impaired hepatic secretion. Clin Chim Acta 168:199–208, 1987
Vyvoda OS, Coleman R, Holdsworth G: Effects of different bile salts upon the composition and morphology of a liver plasma membrane preparation rich in bile canaliculi: Deoxycholate is more membrane damaging than cholate and its conjugates. Biochim Biophys Acta 465:68–76, 1977
Hatoff DE, Hardison WGM: Bile acid-dependent secretion of alkaline phosphatase in rat bile. Hepatology 2:433–439, 1982
Roda E, Roda A, Sama C, Festi D, Mazzella G, Aldini R, Barbara L: Effect of ursodeoxycholic acid administration on biliary lipid composition and bile acid kinetics in cholesterol gallstone patients. Dig Dis Sci 24:123–128, 1979
Hardison WGM, Grundy SM: Effect of ursodeoxycholate and its taurine conjugates on bile acid synthesis and cholesterol absorption. Gastroenterology 87:130–135, 1984
Nilsell K, Angelin B, Barbro L, Einarsson K: Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion in humans. Gastroenterology 85:1248–1256, 1983
La Russo NF, Hoffman NE, Hofmann AF, Northfield TC, Thistle JF: Effect of primary bile acid ingestion on bile acid metabolism and biliary secretion in gallstone patients. Gastroenterology 69:1301–1314, 1975
Tint GS, Salen G, Shefer S: Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism. Gastroenterology 91:1007–1018, 1986
Stiehl A, Raedsch R, Rudolph G: Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 98:424–428, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mazzella, G., Parini, P., Bazzoli, F. et al. Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. Digest Dis Sci 38, 896–902 (1993). https://doi.org/10.1007/BF01295917
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01295917