Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study

Mitchell SA, Thyssen M, Orchard TR, Jewell DP, Fleming KA, Chapman RW. Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study. Gut. 2002 Oct;51(4):567-73. doi: 10.1136/gut.51.4.567. PMID: 12235082; PMCID: PMC1773401.

Abstract Background and aims: The strong clinical association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) suggests common factors in their pathogenesis. Smoking, previous appendectomy, and tonsillectomy have been associated with a decreased risk of developing UC. In this study, our aim was to examine these risk factors in patients with PSC with and without underlying inflammatory bowel disease (IBD). Methods: The smoking habits and history of previous appendectomy and/or tonsillectomy of 170 patients with PSC, 41 without underlying IBD, 170 patients with UC but normal liver function tests, and 170 age and sex matched community controls were obtained by questionnaire. Results: A total of 112 PSC patients (66%) had never smoked compared with 66 controls (39%). Only 12 PSC patients (7%) were current smokers versus 43 controls (25%). The resultant odds ratio of having PSC was 0.17 (95% confidence interval (CI) 0.08-0.35) among current smokers and 0.33 (95% CI 0.21-0.52) among ever (former+current) smokers. Among former smokers, the odds of having PSC were also significantly decreased (odds ratio 0.45, 95% CI 0.26-0.73; p<0.05). In the subgroup of PSC patients without IBD, only 5% were current smokers versus 26% of matched controls, and never smokers were overrepresented (68% v 37%). The rate of previous appendectomy was similar in all three study groups (14%, 12%, and 13%) but the frequency of tonsillectomy was reduced in the PSC group (21% v 31%; p=0.05). Conclusion: PSC, like UC, is a disease of non-smokers as the odds of having PSC was significantly decreased among current and former smokers. The association between non-smoking and PSC was independent of whether the PSC patient had underlying IBD. Previous tonsillectomy but not appendectomy may also be associated with a decreased risk of PSC but this warrants further study.

Primary sclerosing cholangitis is associated with nonsmoking: a case-control study

Loftus EV Jr, Sandborn WJ, Tremaine WJ, Mahoney DW, Zinsmeister AR, Offord KP, Melton LJ 3rd. Primary sclerosing cholangitis is associated with nonsmoking: a case-control study. Gastroenterology. 1996 May;110(5):1496-502. doi: 10.1053/gast.1996.v110.pm8613055. PMID: 8613055.

Abstract Background & aims: Cigarette smoking is thought to protect against the development of ulcerative colitis. The relationship between a related disease, primary sclerosing cholangitis, and smoking is unknown. The aim of this study was to determine if the relationship between smoking and sclerosing cholangitis is similar to that found between smoking and ulcerative colitis. Methods: A stratified sample of 184 patients with primary sclerosing cholangitis and age- and sex-matched institutional control subjects were identified. Smoking information was obtained from a medical questionnaire completed at the time of visit. Results: Eighty-one percent of the patients had associated inflammatory bowel disease. Only 4.9% of them were current smokers compared with 26.1% of the controls; 69.6% of the patients had never smoked vs. 46.7% of the controls. The estimated odds of having primary sclerosing cholangitis in current smokers compared with never-smokers was 0.13. The odds of having disease among former and current users of any tobacco relative to never-users was 0.41 regardless of the presence or absence of inflammatory bowel disease. Conclusions: The odds of having primary sclerosing cholangitis was significantly decreased among current smokers. Concomitant ulcerative colitis does not fully explain the association between nonsmoking and primary sclerosing cholangitis. Smoking may exert its protective effect in a systemic, rather than colonic, manner.

Risk of primary sclerosing cholangitis is associated with nonsmoking behavior

van Erpecum KJ, Smits SJ, van de Meeberg PC, Linn FH, Wolfhagen FH, vanBerge-Henegouwen GP, Algra A. Risk of primary sclerosing cholangitis is associated with nonsmoking behavior. Gastroenterology. 1996 May;110(5):1503-6. doi: 10.1053/gast.1996.v110.pm8613056. PMID: 8613056.

Abstract Background & aims: Seventy percent of patients with primary sclerosing cholangitis (PSC) have concomitant ulcerative colitis. Smoking and previous appendectomy may protect against ulcerative colitis. The aim of this study was to examine these factors in patients with PSC. Methods: Fifty-nine patients with PSC, 130 patients with ulcerative colitis and normal liver biochemistry, and 197 control subjects were interviewed about smoking behavior and history of appendectomy. Results: There were less current smokers in the PSC and ulcerative colitis groups than in the control group (19%, 12%, and 38%, respectively). The resulting odds ratio for current smoking was 0.37 (95% confidence interval, (0.18-0.76) in the PSC group and 0.23 (95% confidence interval, 0.13-0.41) in the ulcerative colitis group. Percentage of persons who ever smoked was also significantly less in the PSC group (41% vs. 56% in the control group). Frequency of previous appendectomy in the PSC and ulcerative colitis groups was not significantly different from that of controls (19%, 9%, and 14%, respectively). Conclusions: Smoking but not previous appendectomy is associated with decreased risk of PSC.

Effects of coffee consumption, smoking, and hormones on risk for primary sclerosing cholangitis

Andersen IM, Tengesdal G, Lie BA, Boberg KM, Karlsen TH, Hov JR. Effects of coffee consumption, smoking, and hormones on risk for primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2014 Jun;12(6):1019-28. doi: 10.1016/j.cgh.2013.09.024. Epub 2013 Sep 25. PMID: 24076415.

Abstract Background & aims: Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC. Methods: A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (control subjects). Data were analyzed from 240 patients with PSC and 245 control subjects, matched for gender and age. Results: A lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P = .003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P < .001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and being a coffee drinker at the age of 18 years (P = .048) were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception (51% vs 85%; P < .001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63; P < .001). Conclusions: Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.