Ursodiol and the Risk of Colorectal Cancer or Dysplasia in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Meta-analysis

Abstract

Purpose: Patients with primary sclerosing cholangitis (PSC) and colonic inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. Studies in patients with PSC and IBD have yielded conflicting information on the relationship between ursodiol (UDCA) and the risk of colorectal cancer or dysplasia. Methods: A systematic review and meta-analysis of case-control and cohort studies was performed to evaluate the effect of UDCA on the risk of colorectal cancer or dysplasia in adult PSC and IBD patients. A sub-group analysis by UDCA dose was also performed. UDCA exposure for each study was classified into two dose categories using mean UDCA data: “low to medium dose UDCA” (< 25 mg/kg/day) and “high dose UDCA” (> 25 mg/kg/day).Figure: [1959]Results: Inclusion and exclusion criteria, as well as dependent and independent variables, were determined a priori. Data were collected for: cases of colorectal cancer or dysplasia, gender of participants, UDCA treatment dose and duration, age at PSC diagnosis, type of IBD, and duration of IBD. Seven papers, with 707 participants and greater than 5751 person-years of follow-up time, met the criteria for final analysis. The overall pooled relative risk estimate using a random effects model was not statistically significant (RR=0.872, 95% CI 0.508-1.495, p=0.619). A subgroup analysis by UDCA dose in a random effects model did not demonstrate a statistically significant reduction in colorectal cancer or dysplasia risk (RR=0.636, 95% CI 0.378-1.070, p=0.088) with low to medium dose UDCA exposures. Conclusion: UDCA use did not have a statistically significant effect on the risk of colorectal cancer or dysplasia in adult PSC and IBD patients in this meta-analysis, but the UDCA doses used in the studies were heterogeneous. A trend toward decreased colorectal cancer or dysplasia risk was seen in the low to medium dose UDCA studies. Although not statistically significant, the directionality of the results after subgroup analysis by UDCA dose suggests a trend in risk reduction at low to medium dose exposures that requires further investigation.