Increased prevalence of primary sclerosing cholangitis among first-degree relatives Annika Bergquist * , Greger Lindberg, Susanne Saarinen, Ulrika Broome ´ Department of Gastroenterology and Hepatology, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, 141 86 Huddinge, Sweden Background/Aims: The aim of the present study was to investigate the familial occurrence of autoimmune diseases in a large group of patients with primary sclerosing cholangitis (PSC). Methods: All patients with PSC treated at Huddinge University Hospital between 1984 and 1999 were included (nZ145). For every patient with PSC and inflammatory bowel disease (IBD) (nZ126) we randomly selected a control patient with IBD (nZ126), matched for age, sex and type of IBD. A questionnaire comprising information about autoimmune diseases among first-degree relatives was answered by all patients and controls. Results: We identified 22 index cases with PSC from 21 families with a first-degree relative with either chronic liver disease and/or IBD. Five patients with PSC had a first-degree relative with PSC (3.4%). The prevalence of PSC among first-degree relatives was 0.7% (5/717). In siblings the prevalence was 1.5% (4/269). The prevalence of first-degree relatives with autoimmune diseases outside the liver was similar in PSC patients and controls. Conclusions: First-degree relatives of patients with PSC have a PSC prevalence of 0.7%. This represents a nearly 100-fold increased risk of developing PSC compared with the general population, supporting the hypothesis that genetic factors are of importance for development of PSC. q 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. 1. Introduction The aetiology of PSC is unknown but the disease is generally defined as an autoimmune liver disease. This is supported by the presence of autoantibodies and increased levels of specific T-cells found in the portal tracts in the liver [1,2]. In addition, the close association between IBD and PSC, with approximately 80% of PSC patients having a concomitant IBD [3,4], and the fact that patients with PSC have an increased frequency of other autoimmune disorders also speaks in favour of involvement of the immune system in the aetiopathogenesis of PSC [5]. However, PSC lacks some characteristics of autoimmune diseases such as a female preponderance and good response to immunosup- pression. The genetic basis of human autoimmune diseases is receiving increased attention. It is well established that genetic factors play an important role in modulating autoimmune diseases by conferring susceptibility to or providing protection from disease onset, progression and/or severity. The importance of genetic factors for the development of PSC is not fully understood. Studies have shown an association between PSC and HLA alleles such as B8, DR B1*03, and DRB1*13 [6] and this speaks in favour of genetic factors being important for the susceptibility of PSC. Further evidence supporting a genetic predisposition for PSC comes from a few case reports of familial occurrence of PSC [7–9]. However, no evaluation of familial occurrence in a large group of patients with PSC has previously been done. The aim of the present study was to investigate the familial occurrence of autoimmune diseases, including chronic liver diseases, IBD, rheumatoid arthritis, diabetes, thyroid disease and other autoimmune diseases in a large group of patients with PSC. Since PSC is strongly associated with IBD we also studied a control group of patients with IBD Journal of Hepatology 42 (2005) 252–256 www.elsevier.com/locate/jhep 0168-8278/$30.00 q 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2004.10.011 Received 2 June 2004; received in revised form 20 September 2004; accepted 19 October 2004; available online 2 November 2004 * Corresponding author. Tel.: C46 8 585 86999; fax: C46 8 585 82335. E-mail address: annika.bergquist@medhs.ki.se (A. Bergquist). Abbreviations IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis; PBC, primary biliary cirrhosis; UC, ulcerative colitis; CD, Crohn’s disease; ERCP, endoscopic retrograde cholangio pancreatico graphy; MRCP, magnetic resonance cholangio pancreatico graphy.