title: No Evidence That Azathioprine Increases Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  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: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: rzenouzi@uke.de.
authors: Roman
authors: R
authors: Zenouzi
authors: Department of Internal Medicine 1, University of Bonn, Bonn, Germany.
authors: Tobias J
authors: TJ
authors: Weismüller
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
authors: Kristin K
authors: KK
authors: Jørgensen
authors: Biostatistics Department, Rouen University Hospital-Charles Nicolle, Rouen, France.
authors: Michael
authors: M
authors: Bubenheim
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Henrike
authors: H
authors: Lenzen
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Peter
authors: P
authors: Hübener
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Kornelius
authors: K
authors: Schulze
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Christina
authors: C
authors: Weiler-Normann
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Marcial
authors: M
authors: Sebode
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Hanno
authors: H
authors: Ehlken
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Nadine
authors: N
authors: Pannicke
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Johannes
authors: J
authors: Hartl
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Moritz
authors: M
authors: Peiseler
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Sina
authors: S
authors: Hübener
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors: Tom H
authors: TH
authors: Karlsen
authors: Norwegian Primary Sclerosing Cholangitis Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: Kirsten M
authors: KM
authors: Boberg
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Michael P
authors: MP
authors: Manns
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Ansgar W
authors: AW
authors: Lohse
authors: 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: cschramm@uke.de.
authors: Christoph
authors: C
authors: Schramm
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use*; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000453:epidemiology*; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: Bile Duct Tumor; Dysplasia; Immunosuppressant; Surveillance; Thiopurines