Ursodiol Use Is Associated with Lower Prevalence of Colonic Neoplasia in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

  1. Bruce Y. Tung, MD;
  2. Mary J. Emond, PhD;
  3. Rodger C. Haggitt, MD;
  4. Mary P. Bronner, MD;
  5. Michael B. Kimmey, MD;
  6. Kris V. Kowdley, MD; and
  7. Teresa A. Brentnall, MD
  1. From University of Washington School of Medicine, Seattle, Washington.

    Abstract

    Background: Patients with ulcerative colitis and primary sclerosing cholangitis are at high risk for colonic dysplasia and cancer. This risk approaches 50% after 25 years of colitis. Ursodiol has been shown to protect against development of colorectal neoplasia in animal models.

    Objective: To assess the relationship between ursodiol use and colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis.

    Design: Cross-sectional study.

    Setting: University medical center.

    Patients: 59 patients with ulcerative colitis and primary sclerosing cholangitis who were undergoing colonoscopic surveillance for colonic dysplasia.

    Measurements: Use of ursodiol was assessed in all patients. The presence or absence of colonic dysplasia was evaluated by colonoscopic surveillance. Other variables assessed were age at onset and duration of ulcerative colitis; duration of primary sclerosing cholangitis; Child–Pugh classification; and use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, and methotrexate.

    Results: Ursodiol use was strongly associated with decreased prevalence of colonic dysplasia (odds ratio, 0.18 [95% CI, 0.05 to 0.61]; P = 0.005). The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01). Younger age at onset of colitis was associated with an increased risk for dysplasia.

    Conclusions: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted.

    Article and Author Information

    • †Deceased.

    • Note: This manuscript honors the memory of Rodger C. Haggitt, one of the coauthors. His contribution to these research efforts has been invaluable, and he will be deeply missed by colleagues, friends, and family.

    • Disclosure: Dr. Kowdley is on the Speakers' Bureau for Axcan Schwartz, a manufacturer of ursodiol, and receives research support from them. Axcan Schwartz is providing ursodiol for a prospective study by these authors of the chemoprotective role of ursodiol in ulcerative colitis.

    • Grant Support: By grants R01CA68124 and P01CA74184 from the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

    • Requests for Single Reprints: Teresa A. Brentnall, MD, Division of Gastroenterology, University of Washington, 1959 NE Pacific Street, Box 356424, Seattle, WA 98195; e-mail, teribr{at}u.washington.edu.

    • Current Author Addresses: Drs. Tung, Kimmey, Kowdley, and Brentnall: Division of Gastroenterology, University of Washington, 1959 NE Pacific Street, Box 356424, Seattle, WA 98195.

    • Dr. Emond: Department of Biostatistics, University of Washington, 1959 NE Pacific Street, Box 357232, Seattle, WA 98195.

    • Dr. Bronner: Department of Pathology, University of Washington, 1959 NE Pacific Street, Box 356100, Seattle, WA 98195.

    • Author Contributions: Conception and design: B.Y. Tung, M.J. Emond, R.C. Haggitt, M.P. Bronner, M.B. Kimmey, K.V. Kowdley, T.A. Brentnall.

    • Analysis and interpretation of the data: B.Y. Tung, M.J. Emond, T.A. Brentnall.

    • Drafting of the article: B.Y. Tung, M.J. Emond, T.A. Brentnall.

    • Critical revision of the article for important intellectual content: B.Y. Tung, M.J. Emond, R.C. Haggitt, M.P. Bronner, M.B. Kimmey, K.V. Kowdley, T.A. Brentnall.

    • Final approval of the article: B.Y. Tung, M.J. Emond, R.C. Haggitt, M.P. Bronner, M.B. Kimmey, K.V. Kowdley, T.A. Brentnall.

    • Provision of study materials or patients: M.B. Kimmey, K.V. Kowdley, T.A. Brentnall.

    • Statistical expertise: M.J. Emond.

    • Collection and assembly of data: B.Y. Tung, R.C. Haggitt, M.P. Bronner, M.B. Kimmey, K.V. Kowdley.

    Summary for Patients

    • Summaries for Patients:Ursodiol Is Associated with Fewer Precancerous Abnormalities of the Colon in Certain Patients with Ulcerative Colitis Ann Intern Med January 16, 2001 134:S69
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    1. Ann Intern Med January 16, 2001 vol. 134 no. 2 89-95
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