High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

Abstract

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.

Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

“…However, this result contrasts with studies by Sjöqvist et al and Wolf et al which found no protective effect of UDCA (Sjöqvist et al, 2004;Wolf et al, 2005). In addition, higher doses of UDCA (28-30 mg/kg body weight/day) have been recently associated to an increased risk of CAC in UC patients with PSC (Eaton et al, 2011). Therefore, at the present time, the protective role of UDCA remains controversial and it could not be recommended as a chemopreventive treatment, at least at doses higher than 15 mg/kg body weight/day.…”

Carcinogenesis in Ulcerative Colitis

“…A prospective, randomised control trial of ursodeoxycholic acid in patients with ulcerative colitis and PSC, demonstrated significantly lower rates of colorectal dysplasia and cancer in the treatment group, with an odds ratio of 0.26 (95% CI, 0.06-0.92; P < 0.03) (Pardi et al, 2003). However other studies have not confirmed this observed reduction (Wolf et al, 2005), and a recent long-term study of patients with UC and PSC taking high dose ursodeoxycholic acid reported an increased rate of colorectal neoplasia (Eaton et al, 2011). Thus this is a controversial area and longterm ursodeoxycholic acid cannot currently be recommended as chemoprevention in patients with ulcerative colitis (Chapman et al, 2010).…”

Colorectal Adenocarcinoma and Inflammatory Bowel Disease: An Update and Review

“…Follow-up studies have demonstrated mixed results [77][78][79], with some studies even noting an increase CRC risk in when high-doses of ursodoxycholic acid were employed [80].…”