Abstract
Ursodeoxycholic acid (UDCA) has been reported to improve liver function tests when administered to patients with cholestatic liver diseases, such as primary biliary cirrhosis (PBC). However, its effects on biliary lipid metabolism in patients with PBC are still unknown. In this study we report the effect that UDCA (600 mg/day, for four weeks) had on biliary cholesterol saturation index, biliary bile acid pattern and pool size, and biliary lipid output in seven female patients (ages 34–58 years) with PBC, stages I to III. A significant improvement of liver function tests was observed after four weeks of treatment. Saturation index was significantly decreased from 1.23±0.1 to 0.7±0.08 (P<0.02); this effect was due to the significant decrease of biliary cholesterol concentration from 6.7±0.36 to 3.6±0.37 percent molar (P<0.02). A significant decrease of cholesterol output (from 88±9 to 55±10 μmol/hr, P<0.02) was also observed. The amount of cholic acid, the predominant bile acid in bile, significantly decreased (from 47.3±3.5 to 35.4±2.6 percent molar, P<0.02), as did amounts of chenodeoxycholic and deoxycholic acids, while the amount of UDCA rose from 1.6±1.0 to 34.0±1.3 percent molar (P<0.02). Total bile acid pool size was not affected by UDCA, but the evaluation of individual bile acid pool sizes showed an increased proportion of UDCA relative to the endogenous bile acids. The results of the study confirm the beneficial effect of UDCA on liver function tests in PBC patients and support the hypothesis that the improvement of these measurements may be due to replacement of toxic endogenous bile acids with UDCA.
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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
Leuschner U, Fischer H, Kurtz W, Gatzen M, Hubner K, Strohm WD, Hellstern A, Guldutuna S, Leuschner M: Ursodeoxycholic acid (UDCA) treatment of primary biliary cirrhosis (PBC): Preliminary results of a controlled randomized prospective double blind trial.In Pathochemistry, Pathophysiology, and Pathomechanics of the Biliary System. Proceedings of a symposium, March 14–16, Bologna, Italy, 1988, p. 50
Podda M, Battezzati PM, Gezzi C, Crosignani A, Bertolini E, Petroni ML, Camisasca M, Zuin M: Ursodeoxycholic acid (UDCA) in chronic liver disease: A dose response study.In Pathochemistry, Pathophysiology, and Pathomechanics of the Biliary System. Proceedings of a symposium, March 14–16, Bologna, Italy, 1988, p 49
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. Proceedings of a Symposium. G Paumgartner, A Stiehl (eds). Lancaster, England, MTP Press (in press)
Grundy SM, Metzger AL: A physiological method for estimation of hepatic secretion of biliary lipids in man. Gastroenterology 62:1200–1217, 1972
Roda A, Festi D, Sama C, Mazzella G, Aldini R, Roda E, Barbara L: Enzymatic determination of cholesterol in bile. Clin Chim Acta 64:377–381, 1975
Fausa O, Skalhegg BA: Quantitative determination of bile acids and their conjugates using thin layer chromatography and a purified 3 alpha-hydroxysteroid-dehydrogenase. Scand J Gastroenterol 9:249–254, 1974
Roda A, Geminiani S, Rossi R, Festi D, Roda E, Barbara L: Enzymatic determination of phospholipids in bile. Lab J Res Med 2:119–122, 1975
Hyden S: A turbidimetric method for determination of higher polyethylene glycols in biological materials. Ann R Agric Coll Sved 22:139–149, 1955
Abell LL, Levy BB, Brodie BB: Cholesterol in serum.In Standard Methods of Clinical Chemistry, Vol 2. D Saligson (ed). New York, Academic Press, 1958, pp 26–33
Grundy SM: Effects of polyunsaturated fats on lipid metabolism in patients with hypertrigliceridemia. J Clin Invest 55:269–282, 1975
Bennion LJ, Grundy SM: Effect of obesity and caloric intake on biliary metabolism in man. J Clin Invest 56:996–1011, 1975
Shaffer EA, Small DM: Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest 59:828–840, 1977
Van Berge-Henegouwen GP, Ruben A, Brandt K-H: Quantitative analysis of bile acids in serum and bile using gasliquid chromatography. Clin Chim Acta 54:249–261, 1974
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 E, Mazzella G, Roda A, Aldini R, Festi D, Bazzoli F, Messale E, Morselli AM, Barbara L: Effect of chenodeoxycholic and ursodeoxycholic acid administration on biliary lipid secretion in normal weight and obese gallstone patients.In Bile Acids and Lipids. G Paumgartner, A Stiehl, W Gerok (eds). Lancaster, England, MTP Press, 1981, pp 189–193
Nilsell K, Angelin B, Leijd B, Einarsson K: Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid in bile acid kinetics and biliary lipid secretion in humans. Evidence for different modes of action on bile acid synthesis. Gastroenterology 86:1248–1256, 1983
Schölmerich J, Becher MS, Schmidt K, Schubert R, Kremer B, Feldhaus S, Gerok W: Influence of hydroxylation and conjugation of bile salts on their membrane damaging properties. Studies on isolated hepatocytes and lipid membrane vesicles. Hepatology 4:661–666, 1984
Kitani K, Ohta M, Kanai S: Tauroursodeoxycholate prevents biliary excretion of protein induced by taurocholate and tauroursodeoxycholate in the rat. Hepatology 3:810, 1983
Kanai S, Kitani K: Glycoursodeoxycholate (GU) is as effective as tauroursodeoxycholate (TU) in preventing taurocholate (TC)-induced cholestasis in the rat. Hepatology 3:811, 1983
Krol, Kitamura T, Miyai K, Hardison W: Tauroursodeoxycholate (TUDC) reduces ductular proliferation and portal inflammation in bile-ductligated hamsters. Hepatology 3:881, 1983
Roda A, Fini A, Grigolo B, Simoni P, Rusticali GA, Natalini B: Factor analysis of physico-chemical properties of bile acids. Ann Chim 78:15–23, 1988
Sherlock S: Primary biliary cirrhosis.In Liver and Bile. L Bianchi, W Gerok, U Sickinger (eds). Lancaster, England, MTP Press, 1977, pp 319–326
Bouchier IAD: Postmortem study of the frequency of gallstones in patients with cirrhosis of the liver. Gut 10:705–710, 1969
Van Berge-Henegouwen GP, Brandt K-H, Ruben THA, Schalm SW, Tall B: High frequency of lithogenic bile in primary biliary cirrhosis. Neth J Med 25:89–93, 1982
Roda E, Bazzoli F, Mazzella G, Villanova N, Simoni P, Festi D, Frabboni R, Ronchi M, Barbara L: Effect of age and sex on bile acid metabolism and biliary lipid secretion in normal subjects and gallstone patients.In Bile Acids and the Liver. G Paumgartner, A Stiehl, W Gerok (eds). Lancaster, England, MTP Press, 1987, pp 225–227
Stiehl A, Ast E, Czygan P, Frohling W, Raedsch R, Kommerel B: Pool size, synthesis and turnover of sulfated and nonsulfated cholic acid and chenodeoxycholic acid in patients with cirrhosis of the liver. Gastroenterology 74:572–577, 1978
Barbara L, Roda A, Roda E, Aldini R, Mazzella G, Festi D, Sama C: Diurnal variations of serum primary bile acids in healthy subjects and hepatobiliary disease patients. Rendic Gastroenterol 8:194–198, 1976
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Roda, E., Mazzella, G., Bazzoli, F. et al. Effect of ursodeoxycholic acid administration on biliary lipid secretion in primary biliary cirrhosis. Digest Dis Sci 34 (Suppl 12), S52–S58 (1989). https://doi.org/10.1007/BF01536664
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DOI: https://doi.org/10.1007/BF01536664