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 also can have inflammatory bowel diseases (IBDs) or features of autoimmune hepatitis (AIH), and therefore are treated with azathioprine. Azathioprine has been associated with an increased risk for malignancy, therefore 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 and Norway. We analyzed data from 638 patients (70% men; 5900 patient-years of follow-up evaluation); 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 end points were present.

RESULTS:

Of patients who received azathioprine treatment, 3.3% developed CCA, compared with 6.8% of patients without azathioprine treatment. However, azathioprine did not significantly affect the risk for CCA (hazard ratio, 0.96; 95% confidence interval, 0.29-3.13; P = .94). The only factor associated with an increased risk of CCA was age 35 years or older at PSC diagnosis (hazard ratio, 3.87; 95% confidence interval, 1.96-7.67; P < .01). Patient sex, concomitant IBD, or AIH did not affect the risk of CCA. Overall, the cumulative 10-year incidence of CCA was 4.6% and the cumulative 15-year incidence was 7.7%.

CONCLUSIONS:

A retrospective analysis of patients with PSC treated at tertiary centers in Europe found no evidence that azathioprine significantly affects the risk of CCA. Azathioprine therefore should not be withheld from patients with PSC and concomitant IBD and/or AIH.

• Authors: Roman Zenouzi, Tobias J Weismüller, Kristin K Jørgensen, Michael Bubenheim, Henrike Lenzen, Peter Hübener, Kornelius Schulze, Christina Weiler-Normann, Marcial Sebode, Hanno Ehlken, Nadine Pannicke, Johannes Hartl, Moritz Peiseler, Sina Hübener, Tom H Karlsen, Kirsten M Boberg, Michael P Manns, Ansgar W Lohse, Christoph Schramm
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 14 Issue 12 Pg. 1806-1812 (12 2016) ISSN: 1542-7714 [Electronic] United States
• PMID: 27521513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Azathioprine

Topics

• Adult
• Azathioprine (adverse effects, therapeutic use)
• Cholangiocarcinoma (chemically induced, epidemiology)
• Cholangitis, Sclerosing (complications, drug therapy)
• Female
• Germany (epidemiology)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Male
• Middle Aged
• Norway (epidemiology)
• Retrospective Studies
• Risk Assessment
• Tertiary Care Centers
• Young Adult