Skip to main content
Gut logoLink to Gut
. 1995 Jun;36(6):935–938. doi: 10.1136/gut.36.6.935

Characterisation of patients with a complete biochemical response to ursodeoxycholic acid.

R A Jorgensen 1, E R Dickson 1, A F Hofmann 1, S S Rossi 1, K D Lindor 1
PMCID: PMC1382637  PMID: 7615288

Abstract

Ursodeoxycholic acid (UDCA) leads to biochemical and clinical improvement in many patients with primary biliary cirrhosis (PBC); although, the response is variable. This study compared UDCA treated patients with complete normalisation of biochemical functions to those without such improvement. Of the 65 patients receiving UDCA, 12 (19%) showed normalisation of liver biochemical functions at two years. The remaining 53 patients showed a less complete response. Mean (SD) alkaline phosphatase and total serum bilirubin values were significantly lower at entry in the patients whose liver biochemistry tests normalised (912 (732) U/l v 1417 (1021) U/l, p = 0.003, and 0.7 (12.1 (5.2) mumol/l v 38.9 (48.5) mumol/l, p = 0.0002, respectively), and percentage of UDCA in biliary bile acid was higher (56.3 (9.5)% v 38.3 (21.1)%, p = 0.03). Patients with biochemically and histologically less severe disease, and greater enrichment of biliary bile with UDCA, are more likely to respond favourably to the drug. The main objective of continued study will be to find out if normal liver biochemical functions can retard disease progression. The association of greater UDCA enrichment with complete biochemical responses suggests that higher doses of UDCA should be evaluated.

Full text

PDF
935

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bodenheimer H., Jr, Schaffner F., Pezzullo J. Evaluation of colchicine therapy in primary biliary cirrhosis. Gastroenterology. 1988 Jul;95(1):124–129. doi: 10.1016/0016-5085(88)90300-9. [DOI] [PubMed] [Google Scholar]
  2. Dickson E. R., Fleming T. R., Wiesner R. H., Baldus W. P., Fleming C. R., Ludwig J., McCall J. T. Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med. 1985 Apr 18;312(16):1011–1015. doi: 10.1056/NEJM198504183121602. [DOI] [PubMed] [Google Scholar]
  3. Dickson E. R., Grambsch P. M., Fleming T. R., Fisher L. D., Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. 1989 Jul;10(1):1–7. doi: 10.1002/hep.1840100102. [DOI] [PubMed] [Google Scholar]
  4. Galle P. R., Theilmann L., Raedsch R., Otto G., Stiehl A. Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology. 1990 Sep;12(3 Pt 1):486–491. doi: 10.1002/hep.1840120307. [DOI] [PubMed] [Google Scholar]
  5. Heuman D. M., Vlahcevic Z. R., Pandak W. M., Hylemon P. B., Kim Y. S., Lillienau J., Hofmann A. F. Effect of cholylsarcosine on hepatic cholesterol and bile acid synthesis and bile secretion in rats. Gastroenterology. 1992 Nov;103(5):1641–1648. doi: 10.1016/0016-5085(92)91190-f. [DOI] [PubMed] [Google Scholar]
  6. Hoofnagle J. H., Davis G. L., Schafer D. F., Peters M., Avigan M. I., Pappas S. C., Hanson R. G., Minuk G. Y., Dusheiko G. M., Campbell G. Randomized trial of chlorambucil for primary biliary cirrhosis. Gastroenterology. 1986 Dec;91(6):1327–1334. doi: 10.1016/0016-5085(86)90183-6. [DOI] [PubMed] [Google Scholar]
  7. Kaplan M. M., Alling D. W., Zimmerman H. J., Wolfe H. J., Sepersky R. A., Hirsch G. S., Elta G. H., Glick K. A., Eagen K. A. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med. 1986 Dec 4;315(23):1448–1454. doi: 10.1056/NEJM198612043152304. [DOI] [PubMed] [Google Scholar]
  8. Kaplan M. M. Primary biliary cirrhosis. N Engl J Med. 1987 Feb 26;316(9):521–528. doi: 10.1056/NEJM198702263160907. [DOI] [PubMed] [Google Scholar]
  9. 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 double-blind trial. Gastroenterology. 1989 Nov;97(5):1268–1274. doi: 10.1016/0016-5085(89)91698-3. [DOI] [PubMed] [Google Scholar]
  10. Lillienau J., Schteingart C. D., Hofmann A. F. Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine. J Clin Invest. 1992 Feb;89(2):420–431. doi: 10.1172/JCI115601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lindor K. D., Dickson E. R., Baldus W. P., Jorgensen R. A., Ludwig J., Murtaugh P. A., Harrison J. M., Wiesner R. H., Anderson M. L., Lange S. M. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology. 1994 May;106(5):1284–1290. doi: 10.1016/0016-5085(94)90021-3. [DOI] [PubMed] [Google Scholar]
  12. Ludwig J., Dickson E. R., McDonald G. S. Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol. 1978 Aug 22;379(2):103–112. doi: 10.1007/BF00432479. [DOI] [PubMed] [Google Scholar]
  13. Matloff D. S., Alpert E., Resnick R. H., Kaplan M. M. A prospective trial of D-penicillamine in primary biliary cirrhosis. N Engl J Med. 1982 Feb 11;306(6):319–326. doi: 10.1056/NEJM198202113060602. [DOI] [PubMed] [Google Scholar]
  14. Neuberger J., Christensen E., Portmann B., Caballeria J., Rodes J., Ranek L., Tygstrup N., Williams R. Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis. Gut. 1985 Feb;26(2):114–119. doi: 10.1136/gut.26.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Poupon R. E., Balkau B., Eschwège E., Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med. 1991 May 30;324(22):1548–1554. doi: 10.1056/NEJM199105303242204. [DOI] [PubMed] [Google Scholar]
  16. Rossi S. S., Converse J. L., Hofmann A. F. High pressure liquid chromatographic analysis of conjugated bile acids in human bile: simultaneous resolution of sulfated and unsulfated lithocholyl amidates and the common conjugated bile acids. J Lipid Res. 1987 May;28(5):589–595. [PubMed] [Google Scholar]
  17. Stiehl A., Rudolph G., Raedsch R., Möller B., Hopf U., Lotterer E., Bircher J., Fölsch U., Klaus J., Endele R. Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology. 1990 Sep;12(3 Pt 1):492–497. doi: 10.1002/hep.1840120308. [DOI] [PubMed] [Google Scholar]
  18. Wiesner R. H., Ludwig J., Lindor K. D., Jorgensen R. A., Baldus W. P., Homburger H. A., Dickson E. R. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N Engl J Med. 1990 May 17;322(20):1419–1424. doi: 10.1056/NEJM199005173222003. [DOI] [PubMed] [Google Scholar]
  19. Yoshikawa M., Tsujii T., Matsumura K., Yamao J., Matsumura Y., Kubo R., Fukui H., Ishizaka S. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology. 1992 Aug;16(2):358–364. doi: 10.1002/hep.1840160213. [DOI] [PubMed] [Google Scholar]
  20. van Berge Henegouwen G. P., Brandt K. H., Eyssen H., Parmentier G. Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. Gut. 1976 Nov;17(11):861–869. doi: 10.1136/gut.17.11.861. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES