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Dive into the research topics where Kirsten Muri Boberg is active.

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Featured researches published by Kirsten Muri Boberg.


Hepatology | 2008

Simplified criteria for the diagnosis of autoimmune hepatitis

E. M. Hennes; Mikio Zeniya; Albert J. Czaja; Albert Parés; George N. Dalekos; Edward L. Krawitt; Paulo Lisboa Bittencourt; Gilda Porta; Kirsten Muri Boberg; Harald Hofer; Francesco B. Bianchi; Minoru Shibata; Christoph Schramm; Barbara Eisenmann de Torres; Peter R. Galle; Ian G. McFarlane; H. P. Dienes; Aw Lohse

Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life‐saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobulins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff ≥6) and 81% sensitivity and 99% specificity (cutoff ≥7) in the validation set. Conclusion: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher. (HEPATOLOGY 2008.)


Hepatology | 2010

Diagnosis and management of primary sclerosing cholangitis

Roger W. Chapman; Johan Fevery; Anthony N. Kalloo; David M. Nagorney; Kirsten Muri Boberg; Benjamin L. Shneider; Gregory J. Gores

Preamble This guideline has been approved by the American Association for the Study of Liver Diseases and represents the position of the Association. These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of the recentlypublished world literature on the topic (Medline search); (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines1; (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and the American Gastroenterological Association Policy Statement on Guidelines2; and (4) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventative aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the available evidence supporting the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1).3 The strength of recommendations in the GRADE system are classified as strong (class 1) or weak (class 2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (level A), moderate (level B), or low-quality (level C).


Gastroenterology | 2010

Genome-Wide Association Analysis in Primary Sclerosing Cholangitis

Tom H. Karlsen; Andre Franke; Espen Melum; Arthur Kaser; Johannes R. Hov; Tobias Balschun; Benedicte A. Lie; Annika Bergquist; Christoph Schramm; Tobias J. Weismüller; Daniel Gotthardt; Christian Rust; Eva Philipp; Teresa Fritz; Liesbet Henckaerts; Rinse K. Weersma; Pieter Stokkers; Cyriel Y. Ponsioen; Cisca Wijmenga; Martina Sterneck; Michael Nothnagel; Jochen Hampe; Andreas Teufel; Heiko Runz; Philip Rosenstiel; Adolf Stiehl; Severine Vermeire; Ulrich Beuers; Michael P. Manns; Erik Schrumpf

BACKGROUND & AIMS We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers. METHODS A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). RESULTS The strongest associations were detected near HLA-B at chromosome 6p21 (rs3099844: odds ratio [OR], 4.8; 95% confidence interval [CI], 3.6-6.5; P = 2.6 x 10(-26); and rs2844559: OR, 4.7; 95% CI, 3.5-6.4; P = 4.2 x 10(-26) in the discovery panel). Outside the HLA complex, rs9524260 at chromosome 13q31 showed significant associations in 3 of 4 study panels. Lentiviral silencing of glypican 6, encoded at this locus, led to the up-regulation of proinflammatory markers in a cholangiocyte cell line. Of 15 established ulcerative colitis susceptibility loci, significant replication was obtained at chromosomes 2q35 and 3p21 (rs12612347: OR, 1.26; 95% CI, 1.06-1.50; and rs3197999: OR, 1.22; 95% CI, 1.02-1.47, respectively), with circumstantial evidence supporting the G-protein-coupled bile acid receptor 1 and macrophage-stimulating 1, respectively, as the likely disease genes. CONCLUSIONS Strong HLA associations and a subset of genes involved in bile homeostasis and other inflammatory conditions constitute key components of the genetic architecture of PSC.


Scandinavian Journal of Gastroenterology | 2002

Cholangiocarcinoma in Primary Sclerosing Cholangitis: Risk Factors and Clinical Presentation

Kirsten Muri Boberg; Annika Bergquist; S. Mitchell; Albert Parés; Floriano Rosina; Ulrika Broomé; Roger W. Chapman; O. Fausa; T. Egeland; Giuseppe Rocca; Erik Schrumpf

Background: Primary sclerosing cholangitis (PSC) confers a high risk of cholangiocarcinoma (CC) development. Since patients at risk of CC may be selected for early liver transplantation, it is a challenge to identify any predisposing factors. We compared the presentation and natural history of a large number of PSC patients with and without later CC development to identify features associated with risk of CC. Methods: Clinical and laboratory data from presentation and follow-up were collected from 394 PSC patients from five European countries. The cohort included 48 (12.2%) patients with CC. Results: CC was diagnosed within the first year after diagnosis of PSC in 24 (50%) cases and in 13 (27%) patients at intended liver transplantation. Jaundice, pruritus, abdominal pain and fatigue were significantly more frequent at diagnosis of PSC in the group that developed CC, but not after exclusion of cases diagnosed within the first year. Inflammatory bowel disease was diagnosed at least 1 year before PSC more often among patients with CC development than among those without (90% and 65%, respectively; P = 0.001). The duration of inflammatory bowel disease before diagnosis of PSC was significantly longer in patients who developed CC than in the remaining group (17.4 years and 9.0 years, respectively; P = 0.009 in multivariate analysis). Conclusions: A high proportion of CC cases is diagnosed within the first year after diagnosis of PSC. A long history of inflammatory bowel disease is a risk factor for CC development.


Gastroenterology | 2008

The natural history of small-duct primary sclerosing cholangitis.

Einar Björnsson; Rolf Olsson; Annika Bergquist; Stefan Lindgren; Barbara Braden; Roger W. Chapman; Kirsten Muri Boberg; Paul Angulo

BACKGROUND & AIMS The long-term prognosis of patients with small-duct primary sclerosing cholangitis (PSC) remains incompletely characterized. We aimed at determining the natural history and long-term outcomes of a large number of patients with small-duct PSC. METHODS Data from 83 patients with well-characterized small-duct PSC from several medical institutions in Europe and the United States were combined. Each patient with small-duct PSC was randomly matched to 2 patients with large-duct PSC by age, gender, calendar year of diagnosis, and institution. RESULTS The median age at diagnosis in both groups was 38 years (61% males). Nineteen (22.9%) of the 83 patients with small-duct PSC progressed to large-duct PSC in a median of 7.4 (interquartile range [IQR], 5.1-14) years. One patient with small-duct PSC who progressed to large-duct PSC was diagnosed with cholangiocarcinoma but after progression to large-duct PSC; 20 patients with large-duct PSC developed cholangiocarcinoma. Patients with small-duct PSC had a significantly longer transplantation-free survival compared with large-duct PSC patients (13 years [IQR, 10-17] vs 10 years [IQR, 6-14], respectively; hazard ratio, 3.04; 95% confidence interval: 1.82-5.06; P < .0001). Two patients with small-duct PSC who underwent liver transplantation had recurrence of small-duct PSC in the graft 9 and 13 years, respectively, after transplantation. CONCLUSIONS Small-duct PSC is a disease of progressive potential but associated with a better long-term prognosis as compared with large-duct PSC. Small-duct PSC may recur after liver transplantation. Cholangiocarcinoma does not seem to occur in patients with small-duct PSC, unless the disease has progressed to large-duct PSC.


Nature Genetics | 2011

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Espen Melum; Andre Franke; Christoph Schramm; Tobias J. Weismüller; Daniel Gotthardt; Felix Offner; Brian D. Juran; Jon K. Laerdahl; Verena Labi; Einar Björnsson; Rinse K. Weersma; Liesbet Henckaerts; Andreas Teufel; Christian Rust; Eva Ellinghaus; Tobias Balschun; Kirsten Muri Boberg; David Ellinghaus; Annika Bergquist; Peter Sauer; Euijung Ryu; Johannes R. Hov; Jochen Wedemeyer; Björn Lindkvist; Michael Wittig; Robert J. Porte; Kristian Holm; Christian Gieger; H-Erich Wichmann; Pieter Stokkers

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4–7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10−16 and P = 4.1 × 10−8, respectively).


Genes and Immunity | 2005

Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases.

Marte K. Viken; Silja S. Amundsen; Tore K. Kvien; Kirsten Muri Boberg; I.-M. Gilboe; Vibke Lilleby; Ludvig M. Sollid; Øystein Førre; Erik Thorsby; A Smerdel; B. A. Lie

A functional single nucleotide polymorphism, 1858C>T, in the PTPN22 gene, encoding a tyrosine phosphatase, has been reported to be associated with type I diabetes and some other autoimmune diseases. To further investigate whether this polymorphism may be a general susceptibility factor for autoimmunity, we performed an association study in five different autoimmune diseases, three previously not tested. We found an association with juvenile idiopathic arthritis (OR=1.41; P=0.04), not previously reported, and a tendency for an association with coeliac disease (OR=1.35; P=0.08). In primary sclerosing cholangitis, no association was observed (OR=0.95; P=0.8). Furthermore, we confirmed the increased risk in rheumatoid arthritis (OR=1.58; P=0.001), but could not find support for an association with systemic lupus erythematosus (OR=0.94; P=0.8). Altogether, we have provided further evidence of an association between autoimmune diseases and the 1858C>T polymorphism in PTPN22.


Journal of Hepatology | 2012

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

Trine Folseraas; Espen Melum; Philipp Rausch; Brian D. Juran; Eva Ellinghaus; Alexey Shiryaev; Jon K. Laerdahl; David Ellinghaus; Christoph Schramm; Tobias J. Weismüller; Daniel Gotthardt; Johannes R. Hov; O. P. F. Clausen; Rinse K. Weersma; Marcel Janse; Kirsten Muri Boberg; Einar Björnsson; Hanns-Ulrich Marschall; Isabelle Cleynen; Philip Rosenstiel; Kristian Holm; Andreas Teufel; Christian Rust; Christian Gieger; H-Erich Wichmann; Annika Bergquist; Euijung Ryu; Cyriel Y. Ponsioen; Heiko Runz; Martina Sterneck

BACKGROUND & AIMS A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). METHODS We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. RESULTS Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication) <0.05) in the replication. The most robust novel association was detected at chromosome 1p36 (rs3748816; p(combined)=2.1 × 10(-8)) where the MMEL1 and TNFRSF14 genes represent potential disease genes. Eight additional novel loci showed suggestive evidence of association (p(repl) <0.05). FUT2 at chromosome 19q13 (rs602662; p(comb)=1.9 × 10(-6), rs281377; p(comb)=2.1 × 10(-6) and rs601338; p(comb)=2.7 × 10(-6)) is notable due to its implication in altered susceptibility to infectious agents. We found that FUT2 secretor status and genotype defined by rs601338 significantly influence biliary microbial community composition in PSC patients. CONCLUSIONS We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC.


Gut | 2002

Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis

Einar Björnsson; Kirsten Muri Boberg; S Cullen; Kenneth A. Fleming; O. P. F. Clausen; O. Fausa; Erik Schrumpf; Roger W. Chapman

Background: Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but a normal cholangiogram are considered to have small duct PSC. The natural history of this condition is unknown. Methods: Thirty three patients with small duct PSC were identified among patients admitted for diagnostic workup of cholestatic liver function tests in one centre in the UK (Oxford) and one centre in Norway (Oslo). A total of 260 patients with large duct PSC were compared, and prognosis in terms of death, cholangiocarcinoma, biochemical features, histological features, and symptoms analysed. Results: Mean age at diagnosis was 38 years and 39 years in small duct and large duct PSC, respectively. Mean follow up was 106 months in small duct and 105 months in large duct patients. Four patients originally considered to have small duct developed large duct PSC. Two of these underwent liver transplantation during follow up. Of the remainder who did not develop large duct PSC, two patients died during follow up: one of liver failure and the other of cardiac death unrelated to her liver disease. A total of 122 (47%) large duct patients either required liver transplantation (34 patients) or died (88 patients). Small duct patients had a significantly better survival compared with large duct patients. Among small duct patients, none developed cholangiocarcinoma compared with 28 of 260 (11%) large duct patients. Conclusions: Patients with small duct PSC seem to have a good prognosis in terms of survival and development of cholangiocarcinoma. Small duct PSC progresses to large duct PSC in a small proportion of patients.


Nature Reviews Gastroenterology & Hepatology | 2016

Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Jesus M. Banales; Vincenzo Cardinale; Guido Carpino; Marco Marzioni; Jesper B. Andersen; Pietro Invernizzi; Guro E. Lind; Trine Folseraas; Stuart J. Forbes; Laura Fouassier; Andreas Geier; Diego F. Calvisi; Joachim C. Mertens; Michael Trauner; Antonio Benedetti; Luca Maroni; Javier Vaquero; Rocio I.R. Macias; Chiara Raggi; M.J. Perugorria; Eugenio Gaudio; Kirsten Muri Boberg; Jose J.G. Marin; Domenico Alvaro

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the “European Network for the Study of Cholangiocarcinoma” (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.

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Erik Schrumpf

Oslo University Hospital

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Tom H. Karlsen

Oslo University Hospital

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Annika Bergquist

Karolinska University Hospital

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Espen Melum

Rikshospitalet–Radiumhospitalet

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Aksel Foss

Oslo University Hospital

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