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Annika Bergquist group

The liver disease Primary Sclerosing Cholangitis (PSC)

We study different aspects on primary sclerosing cholangitis (PSC). PSC is an autoimmune liver disease, characterized by inflammation in intra and extra hepatic bile ducts with close association to inflammatory bowel disease.

We focus our studies on the increased risk of malignancy in PSC in the colon and the liver. We search for and evaluate new diagnostic tools and early markers for malignancy, chemoprevention as well as treatment issues.

Our large cohort of patients of this rare disease provides good opportunities to perform epidemiological, clinical and translational research (see Liver Immunology Lab). We participate in the national study group for liver diseases (SILK), the Nordic liver transplant group (NLTG) and in the International PSC Study Group (IPSCSG) network.

Key words: Primary sclerosing cholangitis, cholangiocarcinoma, colorectal cancer, biomarkers

Members

Annika Bergquist, Group Leader, Adjunct Professor, Senior Consultant and head of the Clinical Department of Gastroenterology and Hepatology, Phone: +46-70-721 4907

Karouk Said, Postdoc

Erik von Seth, Postdoc

Charlotte Söderman, senior forskare, handledare

Lina Lindström, Postdoc

Aris Grigoriadis, PhD-student (CLINTEC)

Aiva Båve, PhD-student

Kajsa Edfors, PhD-student

Amanda Klein, forskningskoordinator

Sirje Laur (SLL), forskningssjuksköterska

Projects

Diagnosis and early markers for malignancy

We are conducting a national surveillance study in patients with PSC where we through consecutive yearly registration of clinical data together with magnetic resonance imaging, colonoscopies and bio-banking search aim for identification of early diagnostic markers for malignancy. One part of this work is performed in collaboration with the International PSC Study Group where we search for genetic markers for disease and risk of malignancy. The utility of cholangioscopy of this purpose is also under evaluation.

Biliary epithelial cells, the immune system and PSC pathogenesis

(Lena Berglin PhD project - see Liver Immunology Lab)

The overall aim is to study how the immune system contributes to the pathogenesis of primary sclerosing cholangitis. One focus is to study the role of autoantibodies in PSC patients, targeted against biliary epithelial cells. Another goal is to characterize the immunogenicity of biliary epithelial cells in PSC patients with respect to natural killer cell recognition.

Aspects on inflammatory bowel disease in PSC

(Lina Lindström PhD project)

The aim is to study inflammatory bowel disease (IBD) in PSC where we specifically aim to study the clinical course and risk of colorectal cancer in PSC- IBD. One focus is the clinical characteristics of Crohn´s disease in PSC. I also aim to assess the risk of colorectal cancer or dysplasia in a large cohort of transplanted patients and to study the potential chemopreventive effect if ursodeoxycholic acid.

Colorectal cancer development: improved early diagnosis and enhanced understanding of pathogenic mechanisms

(Ammar Barakat, PhD project)

PSC is an independent risk factor for development of colorectal cancer (CRC). This project is focused on improving diagnostics for early detection of CRC, as well as enhancing our understanding of why CRC develops. We evaluate the efficacy of laser-based endomicroscopy as a complement to white light colonoscopy for detection of colon dysplasia in patients with PSC-IBD and perform studies of natural killer cell tumor surveillance in dysplastic colon lesions of high-risk PSC-IBD patients.

Diagnosis and treatment of bile duct strictures in primary sclerosing cholangitis

(Erik von Seth PhD project)

Malignant biliary strictures are especially difficult to distinguish from benign in patients with PSC. This project aims to evaluate available diagnostic methods for CCA and outcome in patients with primary sclerosing cholangitis in a prospective study. Furthermore the complications after endoscopic retrograde cholangiography is evaluated using the large nationwide quality register GallRiks.

Selected publications

 

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.
Ellinghaus D, Folseraas T, Holm K, Ellinghaus E, Melum E, Balschun T, et al
Hepatology 2013 Sep;58(3):1074-83

 

Alcohol consumption in patients with primary sclerosing cholangitis.
Hagström H, Stål P, Stokkeland K, Bergquist A
World J. Gastroenterol. 2012 Jun;18(24):3105-11

 

Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study.
Jørgensen K, Lindström L, Cvancarova M, Castedal M, Friman S, Schrumpf E, et al
Scand. J. Gastroenterol. 2012 Sep;47(8-9):1021-9

 

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.
Folseraas T, Melum E, Rausch P, Juran BD, Ellinghaus E, Shiryaev A, et al
J. Hepatol. 2012 Aug;57(2):366-7522521342

 

The value of thioredoxin family proteins and proliferation markers in dysplastic and malignant gallbladders in patients with primary sclerosing cholangitis.
Said K, Glaumann H, Björnstedt M, Bergquist A
Dig. Dis. Sci. 2012 May;57(5):1163-70

 

High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.
Lindström L, Boberg KM, Wikman O, Friis-Liby I, Hultcrantz R, Prytz H, et al
Aliment. Pharmacol. Ther. 2012 Feb;35(4):451-7

 

Increased risk of colorectal cancer and dysplasia in patients with Crohn's colitis and primary sclerosing cholangitis.
Lindström L, Lapidus A, Ost A, Bergquist A
Dis. Colon Rectum 2011 Nov;54(11):1392-7

 

Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.
Janse M, Lamberts LE, Franke L, Raychaudhuri S, Ellinghaus E, Muri Boberg K, et al
Hepatology 2011 Jun;53(6):1977-85

 

Electrostatic modifications of the human leukocyte antigen-DR P9 peptide-binding pocket and susceptibility to primary sclerosing cholangitis.
Hov JR, Kosmoliaptsis V, Traherne JA, Olsson M, Boberg KM, Bergquist A, et al
Hepatology 2011 Jun;53(6):1967-76

 

Pancreatic duct changes are not associated with early signs of chronic pancreatitis at magnetic resonance imaging (MRI) in patients with primary sclerosing cholangitis.
Said K, Albiin N, Lindberg B, Brismar TB, Karrar A, Permert J, et al
Scand. J. Gastroenterol. 2010 Aug;45(7-8):980-6

 

Genome-wide association analysis in primary sclerosing cholangitis.
Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, et al
Gastroenterology 2010 Mar;138(3):1102-11

 

Gallbladder emptying in patients with primary sclerosing cholangitis.
Said K, Edsborg N, Albiin N, Bergquist A
World J. Gastroenterol. 2009 Jul;15(28):3498-503

 

High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.
Olsson R, Glaumann H, Almer S, Broomé U, Lebrun B, Bergquist A, et al
Eur. J. Intern. Med. 2009 Mar;20(2):190-6


 

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.
Bergquist A, Montgomery SM, Bahmanyar S, Olsson R, Danielsson A, Lindgren S, et al
Clin. Gastroenterol. Hepatol. 2008 Aug;6(8):939-43

 

An interleukin-6 (IL-6) receptor polymorphism affecting serum levels of IL-6 does not increase the risk of cholangiocarcinoma in primary sclerosing cholangitis.
Melum E, Karlsen TH, Bergquist A, Schrumpf E, Boberg KM
Am. J. Gastroenterol. 2008 Apr;103(4):1045; author reply 1045-6

 

Annika Bergquist - Adjunct Professor in Gastroenterology and Hepatology

Annika Bergquist - Adjunct Professor in Gastroenterology and Hepatology

Interview with Anna Bergquist in conjunction with her adjunct professorship.