Ursodeoxycholic Acid Treatment in IBD-patients with Colorectal Dysplasia and/or DNA-aneuploidy: a Prospective, Double-blind, Randomized Controlled Pilot Study

Background & Aims: There is an increased risk of colorectal carcinoma (CRC) in patients with longstanding, extensive colonic inflammatory bowel disease (IBD). Primary sclerosing cholangitis, family history of CRC, mucosal dysplasia and DNA-aneuploidy are other risk factors. Recently, results from animal studies have shown that the bile acid ursodeoxycholic acid (UDCA) has a favourable impact on experimentally-induced CRC/neoplasia in rats. The aim of this proof of the concept study was to explore the possible preventive/reverting effects of UDCA in patients with colorectal IBD with existing findings of low grade dysplasia and/or DNA- aneuploidy. Patients and Methods: Nineteen patients (13 UC, 6 CD, median age 43 years) with long-standing, extensive IBD (median duration 21 years), with previous findings of low-grade dysplasia and/or DNA-aneuploidy, were randomized to receive either UDCA (500 mg b.i.d) (n=10) or placebo (n=9) in a controlled, double-blind, two-year study. Colonoscopy with multiple biopsies for histopathology and for DNA-flow cytometry was performed at the start and at six-month intervals during the study period. The primary outcome was the need for colectomy due to progression of dysplasia. Changes in dysplasia and DNA- aneuploidy scores were also assessed. Results: There were no significant differences in the overall composed score between the two groups, either at study start or during the study period. In the placebo group one patient had a progression of dysplasia into high-grade and one patient developed DALM with low- grade dysplasia; both had a colectomy. In contrast, no UDCA- treated patient had progression of dysplasia. Conclusion: UDCA may prevent further progression of manifest low-grade dysplasia in colorectal IBD. Prolonged treatment or an increased dose may be needed to fully exploit the chemopreventive properties of this compound. There is an increased incidence of colorectal carcinoma (CRC) in patients with long-standing, extensive ulcerative colitis (UC). The cumulative risk for CRC is 10-15% after 25