Ursodeoxycholic acid therapy in primary biliary cirrhosis.

In a total of 1004 patients in 11 controlled trials, treatment with ursodeoxycholic acid (UDCA) 8-15 mg/kg bodyweight per day led to a decrease of pruritus in 30-60% of cases, a decrease in aminotransferases and cholestasis-indicating enzymes in serum by 20-80%, and a decrease of serum bilirubin by 3-40%. A statistically significant improvement in liver histology was found in only two of these studies; in three others there was a positive trend. In three more trials histology was not examined, and in three studies there was no improvement. In the four studies investigating the time elapsed before liver transplantation and the number of deaths, only one definitely found that this was prolonged by UDCA, although in two of the other three there was a positive trend. During treatment, UDCA constitutes 30-50% of the total bile acids in bile and serum; however, its influence on the toxic bile acids is debatable. Cholic acid decreases, but deoxycholic acid and chenodeoxycholic acid are reduced to a lesser degree. UDCA therapy has now been practiced for 12 years and all authors consider the treatment to be safe, but the mode of action of UDCA is still unknown.

[1]  K. Hübner,et al.  Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late stages of primary biliary cirrhosis. , 1994, Journal of hepatology.

[2]  S. Kuriyama,et al.  Effects of ursodeoxycholic acid on antigen presentation , 1993 .

[3]  U. Leuschner,et al.  Molecular aspects of membrane stabilization by ursodeoxycholate , 1993 .

[4]  R. Sokol,et al.  Evidence for involvement of oxygen free radicals in bile acid toxicity to isolated rat hepatocytes , 1993, Hepatology.

[5]  Y. Chrétien,et al.  Serum bile acids in primary biliary cirrhosis: Effect of ursodeoxycholic acid therapy , 1993, Hepatology.

[6]  J. Boyer,et al.  Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes. , 1993, Gastroenterology.

[7]  J. Senior,et al.  Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. , 1993, The American journal of gastroenterology.

[8]  W. Gerok,et al.  Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. , 1993, Journal of hepatology.

[9]  W. Pandak,et al.  Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: In vitro studies in rat hepatocytes and human erythrocytes , 1991, Hepatology.

[10]  Y. Nakanuma,et al.  Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy. , 1991, The American journal of gastroenterology.

[11]  K. Einarsson,et al.  Effect of ursodeoxycholic acid treatment on ileal absorption of bile acids in man as determined by the SeHCAT test. , 1991, Gut.

[12]  P. Hylemon,et al.  Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. , 1991, Gastroenterology.

[13]  J. Bircher,et al.  Ursodeoxycholic acid–induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis , 1990, Hepatology.

[14]  P. Galle,et al.  Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes , 1990, Hepatology.

[15]  É. Doucet,et al.  Bile acids mobilise internal Ca2+ independently of external Ca2+ in rat hepatocytes. , 1990, European journal of biochemistry.

[16]  S. Erlinger Hypercholeretic bile acids: A clue to the mechanism? , 1990, Hepatology.

[17]  S. Orrenius,et al.  Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver. , 1990, The Journal of clinical investigation.

[18]  P. Gane,et al.  Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: Effect of ursodeoxycholic acid , 1990, Hepatology.

[19]  S. Katz,et al.  Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. , 1989, Journal of lipid research.

[20]  M. Anwer,et al.  Hepatotoxic bile acids increase cytosolic Ca++ activity of isolated rat hepatocytes , 1988, Hepatology.

[21]  L. Combettes,et al.  Release of calcium from the endoplasmic reticulum by bile acids in rat liver cells. , 1988, The Journal of biological chemistry.

[22]  M. Fayer,et al.  Effect of cholesterol on viscoelastic properties of dipalmitoylphosphatidylcholine multibilayers as measured by a laser-induced ultrasonic probe. , 1986, Biochemistry.

[23]  P. Yeagle Cholesterol and the cell membrane. , 1985, Biochimica et biophysica acta.

[24]  W. Hardison,et al.  Bile Acid‐Dependent Secretion of Alkaline Phosphatase in Rat Bile , 2007, Hepatology.

[25]  K. Kitani,et al.  Tauroursodeoxycholate prevents taurocholate induced cholestasis. , 1982, Life sciences.

[26]  W. Hardison,et al.  Bile Acids Modify Alkaline Phosphatase Induction and Bile Secretion Pressure After Bile Duct Obstruction in the Rat , 1981 .

[27]  S. Massarrat,et al.  Daily fluctuation of cholestatic enzymes in bile and its relationship to the total bile salts concentration. , 1979, Clinical biochemistry.

[28]  K. Miyai,et al.  Subcellular pathology of rat liver in cholestasis and choleresis induced by bile salts. 1. Effects of lithocholic, 3beta-hydroxy-5-cholenoic, cholic, and dehydrocholic acids. , 1977, Laboratory investigation; a journal of technical methods and pathology.

[29]  D. Zakim,et al.  Membrane fluidity and the regulation of membrane-bound enzymes. , 1974, Horizons in biochemistry and biophysics.

[30]  O. Zelder,et al.  Effect of taurocholate, dehydrocholate and secretin on biliary output of alkaline phosphatase and GOT. , 1973, Helvetica medica acta.

[31]  D. Papahadjopoulos,et al.  Phospholipid requirements for (Na + + K + )-ATPase activity: head-group specificity and fatty acid fluidity. , 1972, Biochimica et biophysica acta.

[32]  J. B. Carey,et al.  Relief of the pruritus of jaundice with a bile-acid sequestering resin. , 1961, JAMA.