Autoimmune, Cholestatic, and Biliary Disease

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High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis†

  1. Keith D. Lindor1,‡,*,
  2. Kris V. Kowdley2,
  3. Velimir A. C. Luketic3,
  4. M. Edwyn Harrison4,
  5. Timothy McCashland5,
  6. Alex S. Befeler6,
  7. Denise Harnois7,
  8. Roberta Jorgensen1,
  9. Jan Petz1,
  10. Jill Keach1,
  11. Jody Mooney2,
  12. Carol Sargeant3,
  13. Julie Braaten4,
  14. Tamara Bernard5,
  15. Debra King6,
  16. Ellen Miceli7,
  17. Jeff Schmoll8,
  18. Tanya Hoskin8,
  19. Prabin Thapa8,
  20. Felicity Enders8

Article first published online: 20 MAY 2009

DOI: 10.1002/hep.23082

Issue

Hepatology

Hepatology

Volume 50, Issue 3, pages 808–814, September 2009

Additional Information

How to Cite

Lindor, K. D., Kowdley, K. V., Luketic, V. A. C., Harrison, M. E., McCashland, T., Befeler, A. S., Harnois, D., Jorgensen, R., Petz, J., Keach, J., Mooney, J., Sargeant, C., Braaten, J., Bernard, T., King, D., Miceli, E., Schmoll, J., Hoskin, T., Thapa, P. and Enders, F. (2009), High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology, 50: 808–814. doi: 10.1002/hep.23082

Author Information

  1. 1

    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

  2. 2

    Center for Liver Disease, Virginia Mason Medical Center, Seattle, WA

  3. 3

    Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA

  4. 4

    Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ

  5. 5

    Department of Internal Medicine, University of Nebraska, Lincoln, NE

  6. 6

    Division of Gastroenterology and Hepatology; Saint Louis University, St. Louis, MO

  7. 7

    Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL

  8. 8

    Biostatistics and Health Sciences Research; Mayo Clinic, Rochester, MN

  1. ‡

    fax: 507-266-4531.

*Mayo Clinic, Fiterman Center for Digestive Diseases, 200 First Street, SW, Rochester, MN 55905

  1. †

    Potential conflicts of interest: none.

Publication History

  1. Issue published online: 27 AUG 2009
  2. Article first published online: 20 MAY 2009
  3. Accepted manuscript online: 20 MAY 2009 12:00AM EST
  4. Manuscript Accepted: 11 MAY 2009
  5. Manuscript Received: 19 MAR 2009

Funded by

  • National Institute of Diabetes and Digestive and Kidney Diseases. Grant Number: 56924
  • Axcan Pharma
  • National Center for Research Resources (awarded to Virginia Commonwealth University). Grant Number: M01RR000065

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Abstract

Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (HEPATOLOGY 2009.)

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