title: Risk factors for primary sclerosing cholangitis.
abstract: OBJECTIVE
  Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease of unknown cause, but strongly associated with inflammatory bowel disease (IBD). Potential risk factors triggering PSC have never been studied on a population level. The aim of this study was to evaluate smoking, appendectomy, family history and geographical distribution in a population-based cohort of PSC patients, as compared to IBD control patients and healthy controls (HC).
  
  
  METHODS
  For this case-control study 343 PSC patients, 370 IBD controls and 232 HC's living in a geographically defined area in the Netherlands filled-out a questionnaire concerning smoking, appendectomy and family history of IBD and autoimmune liver diseases.
  
  
  RESULTS
  Smoking was associated with a lower risk of developing PSC in PSC-ulcerative colitis (UC) patients (adjusted OR 0.21; 95% CI 0.12-0.34; P < 0.001). Comparable results were found for PSC-Crohn's disease (CD) patients (16% former smokers) compared to CD patients (55% former smokers) (adjusted OR 0.17; 95% CI 0.08-0.39; P < 0.001). Frequency of appendectomy did not differ between PSC and HC, but PSC-UC patients had undergone appendectomy more often than UC patients (13% vs. 6%) (adjusted OR 2.51; 95%CI 1.04-6.07; P = 0.041). We found no association between family history of IBD or autoimmune liver disease and risk of PSC. Degree of urbanization was not associated with PSC incidence.
  
  
  CONCLUSIONS
  In this large population-based case-control study we confirm that smoking is associated with a lower risk of developing PSC, independent of its protective effect for developing UC. Appendectomy is not associated with the risk of developing PSC.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Boonstra
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Elisabeth M G
authors.initials: EM
authors.lastname: de Vries
authors.affiliation: Clinical Research Unit, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Nan
authors.initials: N
authors.lastname: van Geloven
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Spanier
authors.affiliation: Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Poen
authors.affiliation: Department of Gastroenterology and Hepatology, VU Medical Center, Amsterdam, the Netherlands.
authors.forename: Carin M
authors.initials: CM
authors.lastname: van Nieuwkerk
authors.affiliation: Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, the Netherlands.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Witteman
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center Alkmaar, Alkmaar, the Netherlands.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Tuynman
authors.affiliation: Department of Gastroenterology and Hepatology, Tergooiziekenhuizen, Hilversum/Blaricum, the Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: Naber
authors.affiliation: Department of Gastroenterology and Hepatology, Tergooiziekenhuizen, Hilversum/Blaricum, the Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingma
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
mesh_terms: D000328:Adult; D001062:Appendectomy / Q000706:statistics & numerical data*; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000453:epidemiology*; D003710:Demography; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D065840:Protective Factors; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*
keywords: appendectomy; primary sclerosing cholangitis; risk factors; smoking