No Evidence That Azathioprine Increases Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis

Abstract Background & Aims Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Patients with PSC can also have inflammatory bowel diseases (IBD) or features of autoimmune hepatitis (AIH), and are therefore treated with azathioprine. Azathioprine has been associated with an increased risk for malignancy, so we investigated whether azathioprine use affects the risk of CCA in persons with PSC. Methods We performed a retrospective study of well-defined patients with PSC using data collected from 3 large-volume tertiary care centers in Germany or Norway. We analyzed data from 638 patients (70% male; 5900 patient-years of follow up); 91 patients had received azathioprine therapy (considered to be effective at 90 days after first intake). Risk analysis was performed using the Cox proportional hazard model when risks competing with study endpoints were present. Results Of patients who received azathioprine treatment, 3.3% developed CCA, compared to 6.8% of patients without azathioprine treatment. However, azathioprine did not significantly affect risk for CCA (hazard ratio, 0.96; 95% CI, 0.29–3.13; P =.94). The only factor associated with an increased risk of CCA was age 35 years or more at PSC diagnosis (hazard ratio, 3.87; 95% CI, 1.96–7.67; P