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Azathioprine in PSC does not increase risk for cholangiocarcinoma

Azathioprine did not increase the risk for cholangiocarcinoma in patients with primary sclerosing cholangitis, according to recent findings published in Clinical Gastroenterology and Hepatology.

“This is the first study on cholangiocarcinoma (CCA) development in primary sclerosing cholangitis (PSC) patients investigating azathioprine as a risk factor,” Roman Zenouzi, at the University Medical Center Hamburg-Eppendorf in Germany, and colleagues wrote. “Most investigators believe that CCA in PSC arises through an inflammation-dysplasia-carcinoma sequence. This concept was mainly supported by studies evaluating the frequency of bile duct dysplasia of PSC liver explants.”

Patients with PSC are at increased risk for CCA, the researchers wrote. Further, patients with PSC can have IBD or features of autoimmune hepatitis (AIH), both of which require azathioprine, which has been associated with increased risk for skin cancer and lymphoma.

To assess whether azathioprine increases the risk for CCA in patients with PSC, Zenouzi and colleagues performed a retrospective study of 638 patients with PSC in three tertiary care centers in Germany and Norway.

Of the 91 patients who received azathioprine, 3.3% developed CCA vs. 6.8% of the remaining patients. Overall, azathioprine was not significantly associated with increased risk for CCA. Age older than 35 years at PSC diagnosis was associated with an increased risk for CCA (HR = 3.87; 95% CI, 1.96-7.67) whereas sex, concomitant IBD and AIH were not associated. The cumulative 10-year CCA incidence was 4.6% and the 15-year incidence was 7.7%.

The researchers concluded that there was no evidence that azathioprine increases the risk for CCA in these patients. Further, there are no data on the effect of azathioprine on CCA development in other autoimmune liver diseases.

“In patients with PSC and concomitant IBD and/or AIH, treatment with azathioprine should not be withheld,” the researchers wrote. “Furthermore, the relatively low incidence of CCA in PSC patients treated with azathioprine should be reevaluated in a larger multicentric cohort, in order to assess the effect of an anti-inflammatory treatment on CCA development. – by Will Offit

Disclosure: The researchers report no relevant financial disclosures.