A study published in The American Journal of Gastroenterology has demonstrated that high-dose ursodeoxycholic acid (UDCA) is associated with an increased risk of colonic neoplasia in patients with primary sclerosing cholangitis (PSC) and ulcerative colitis.

PSC is a chronic cholestatic liver disease characterized by inflammation of the intrahepatic and extrahepatic bile ducts. Nearly 70% of patient with PSC also have IBD, usually ulcerative colitis. Patients with ulcerative colitis have an increased risk of developing colorectal cancer, and patients with both PSC and ulcerative colitis are at an even higher risk of developing colorectal cancer than patients with ulcerative colitis alone.

UDCA is a synthetic bile acid that is commonly used for the treatment of PSC. “Previous studies have suggested that low doses of UDCA (13–15 mg/kg daily) might reduce the risk of colonic neoplasia,” explains Keith Lindor, one of the authors of the study. “We were interested in what effects we might find with higher doses of UDCA (28–30 mg/kg daily), which have recently been shown to be associated with an increased risk of liver problems in patients receiving this agent for PSC.”

The researchers reviewed pathology and colonoscopy reports from patients with PSC and ulcerative colitis who had been enrolled in a prior, multicenter, randomized, placebo-controlled trial of high-dose UDCA. 56 patients were included in the retrospective review: 25 received UDCA and 31 received placebo.

“To our surprise, long-term use of high-dose UDCA was associated with an increased risk of colorectal neoplasia in patients with PSC and ulcerative colitis,” says Lindor. “This is distinctly different from other studies suggesting that low doses may reduce the risk of colorectal neoplasia.”

More research is now needed into understanding the mechanisms underlying the development of colonic neoplasia in patients with PSC and ulcerative colitis.