Increased Risk of Primary Sclerosing Cholangitis and Ulcerative Colitis in First-Degree Relatives of Patients With Primary Sclerosing Cholangitis

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doi:10.1016/j.cgh.2008.03.016 Copyright © 2008 AGA Institute Published by Elsevier Ltd. Original article—liver, pancreas, and biliary tract

Increased Risk of Primary Sclerosing Cholangitis and Ulcerative Colitis in First-Degree Relatives of Patients With Primary Sclerosing Cholangitis

Annika Bergquist, , , M. Montgomery‡, §, Shahram Bahmanyar‡, Rolf Olsson, Åke sson¶, Stefan Lindgren, Hanne Prytz‡‡, Rolf Hultcrantz, L.A.R.S. Lööf§§, Hanna Sandberg–Gertzén, Sven Almer¶¶, Johan Askling‡, Ehlin‡ and Anders Ekbom‡

‡Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm ‡‡Division of Gastroenterology and Hepatology, University Hospital, Lund Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institute, Huddinge and Solna, Stockholm Department of Gastroenterology and Hepatology, University Hospital, Malmö Department of Medicine, Sahlgrenska University Hospital, Gothenburg Division of Gastroenterology and Hepatology, Department of Medicine, Medical Center Hospital, Örebro §Clinical Research Centre, Örebro University Hospital, Örebro §§Centre for Clinical Research, Central Hospital, Västerås ¶Department of Medicine, Section for Gastroenterology and Hepatology, University Hospital, Umeå ¶¶Division of Gastroenterology and Hepatology/IKE, University Hospital, Linköping, Sweden

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Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC.

Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register.

Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9).

Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Abbreviations: CI, confidence interval; IBD, inflammatory bowel disease; ICD, International Classification of Diseases; PSC, primary sclerosing cholangitis; UC, ulcerative colitis

Article Outline

Subjects and Methods

Index Cohort of Patients With Primary Sclerosing Cholangitis Comparison Cohort First-Degree Relatives of Patients With Primary Sclerosing Cholangitis and of the Comparison Subjects Occurrence of Cholangitis, Ulcerative Colitis, and Crohn′s Disease Statistical Analysis

Results

Risk of Primary Sclerosing Cholangitis in First-Degree Relatives Risk of Inflammatory Bowel Disease in First-Degree Relatives Disease Risk in Relatives of Patients With Primary Sclerosing Cholangitis but Not Inflammatory Bowel Disease

Discussion References

Figure 1. The cohort of first-degree relatives of patients with PSC and of controls.

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Table 1.

Clinical Characteristics of 678 Patients With PSC

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Table 2.

Characteristics of First-Degree Relatives

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Table 3.

PSC Among First-Degree Relatives of Patients With PSC: Events and Risks Compared With First-Degree Relatives of a Comparison Cohorta All patients with cholangitis, including gallbladder disease.b proportional hazard modeling was used, with adjustment for attained age and stratified by risk set, producing hazard ratios (with 95% CIs).c Estimated without stratification as a result of sparse data.d Conditional logistic regression was used, stratified on risk set and producing odds ratios (with 95% CIs).e Because of the structure of the data, this estimate did not change after the exclusions.

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Table 4.

IBD Among First-Degree Relatives of Patients With PSC: Events and Risks Compared With First-Degree Relatives of a Comparison Cohorta proportional hazard modeling was used, with adjustment for attained age and stratified by risk set, producing hazard ratios (with 95% CIs).b Conditional logistic regression was used, stratified on risk set and producing odds ratios (with 95% CIs).

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Table 5.

PSC and IBD Among First-Degree Relatives of Patients With PSC Without IBD: Events and Risks Compared With First-Degree Relatives of a Comparison Cohorta proportional hazard modeling was used, with adjustment for attained age and stratified by risk set, producing hazard ratios (with 95% CIs).b Not estimated because of empty cells.c Conditional logistic regression was used, stratified on risk set and producing odds ratios (with 95% CIs).

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Clinical Gastroenterology and HepatologyVolume 6, Issue 8, August 2008, Pages 939-943