160 results on '"Annika Bergquist"'
Search Results
2. Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis
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Martine Walmsley, Vipul Jairath, Christoph Schramm, Michael Trauner, Christopher Ma, Gideon Hirschfield, Palak J Trivedi, Nasir Hussain, Olalekan Lee Aiyegbusi, Mette Vesterhus, Kris Kowdley, Cyriel Ponsioen, Annika Bergquist, Paula Hanford, Cynthia Levy, David Assis, and Christopher Bowlus
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Medicine - Abstract
Background Primary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging, with several innovative clinical trials in progress. Despite these advancements, there is considerable heterogeneity in the outcomes studied, with lack of consensus as to what outcomes to measure, when to measure and how to measure. Furthermore, there has been a paradigm shift in PSC treatment targets over recent years, moving from biochemistry-based endpoints to histological assessment of liver fibrosis, imaging-based biomarkers and patient-reported outcome measures. The abundance of new interventional trials and evolving endpoints pose opportunities for all stakeholders involved in evaluating novel therapies. To this effect, there is a need to harmonise measures used in clinical trials through the development of a core outcome set (COS).Methods and analysis Synthesis of a PSC-specific COS will be conducted in four stages. Initially, a systematic literature review will be performed to identify outcomes previously used in PSC trials, followed by semistructured qualitative interviews conducted with key stakeholders. The latter may include patients, clinicians, researchers, pharmaceutical industry representatives and healthcare payers and regulatory agencies, to identify additional outcomes of importance. Using the outcomes generated from the literature review and stakeholder interviews, an international two-round Delphi survey will be conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting will be convened to ratify the COS and disseminate findings for application in future PSC trials.Ethics and dissemination Ethical approval has been granted by the East Midlands—Leicester Central Research Ethics Committee (Ref: 24/EM/0126) for this study. The COS from this study will be widely disseminated including publication in peer-reviewed journals, international conferences, promotion through patient-support groups and made available on the Core Outcomes Measurement in Effectiveness Trials (COMET) database.Trial registration number 1239.
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- 2024
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3. The Swedish initiative for the study of Primary sclerosing cholangitis (SUPRIM)Research in context
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Martin Cornillet, Christina Villard, Fredrik Rorsman, Antonio Molinaro, Emma Nilsson, Stergios Kechagias, Erik von Seth, and Annika Bergquist
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Primary sclerosing cholangitis ,Inflammatory bowel disease ,Liver transplantation ,Phenotype ,Outcome ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Despite more than 50 years of research and parallel improvements in hepatology and oncology, there is still today neither a treatment to prevent disease progression in primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, the limited understanding of the underlying biological mechanisms in PSC and its natural history not only affects the identification of new drug targets but implies a lack of surrogate markers that hampers the design of clinical trials and the evaluation of drug efficacy. The lack of easy access to large representative well-characterised prospective resources is an important contributing factor to the current situation. Methods: We here present the SUPRIM cohort, a national multicentre prospective longitudinal study of unselected PSC patients capturing the representative diversity of PSC phenotypes. We describe the 10-year effort of inclusion and follow-up, an intermediate analysis report including original results, and the associated research resource. All included patients gave written informed consent (recruitment: November 2011–April 2016). Findings: Out of 512 included patients, 452 patients completed the five-year follow-up without endpoint outcomes. Liver transplantation was performed in 54 patients (10%) and hepatobiliary malignancy was diagnosed in 15 patients (3%). We draw a comprehensive landscape of the multidimensional clinical and biological heterogeneity of PSC illustrating the diversity of PSC phenotypes. Performances of available predictive scores are compared and perspectives on the continuation of the SUPRIM cohort are provided. Interpretation: We envision the SUPRIM cohort as an open-access collaborative resource to accelerate the generation of new knowledge and independent validations of promising ones with the aim to uncover reliable diagnostics, prognostic tools, surrogate markers, and new treatment targets by 2040. Funding: This work was supported by the Swedish Cancer Society, Stockholm County Council, and the Cancer Research Funds of Radiumhemmet.
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- 2024
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4. Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review
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Annika Bergquist, Carl Jorns, and Christina Villard
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.
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- 2024
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5. Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis
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Jeremy S. Nayagam, Tobias J. Weismüller, Piotr Milkiewicz, Karolina M. Wronka, Emil Bik, Christoph Schramm, Katja Fuessel, Taotao Zhou, Johannes Chang, Martti Färkkilä, Ylva Carlsson, Anastasia Lundman, Nora Cazzagon, Giorgia Corrà, Eirini Rigopoulou, George N. Dalekos, Aiva Lundberg Båve, Annika Bergquist, Karim Ben Belkacem, Marco Marzioni, Martina Mancinelli, Xavier Verhelst, Hanns-Ulrich Marschall, Michael A. Heneghan, and Deepak Joshi
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Primary sclerosing cholangitis ,Intrahepatic cholestasis of pregnancy ,Cholangiopathy ,Pruritus ,Ursodeoxycholic acid ,Bile acids ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.
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- 2024
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6. Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis
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Younghun Han, Jinyoung Byun, Catherine Zhu, Ryan Sun, Julia Y. Roh, Heather J. Cordell, Hyun-Sung Lee, Vikram R. Shaw, Sung Wook Kang, Javad Razjouyan, Matthew A. Cooley, Manal M. Hassan, Katherine A. Siminovitch, Trine Folseraas, David Ellinghaus, Annika Bergquist, Simon M. Rushbrook, Andre Franke, Tom H. Karlsen, Konstantinos N. Lazaridis, The International PSC Study Group, Katherine A. McGlynn, Lewis R. Roberts, and Christopher I. Amos
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Science - Abstract
The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.
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- 2023
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7. Development of a prognostic MRCP-score (DiStrict) for individuals with large-duct primary sclerosing cholangitis
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Aristeidis Grigoriadis, Kristina Imeen Ringe, Johan Bengtsson, Erik Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, and Annika Bergquist
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Cholangitis sclerosing ,Cholangiopancreatography ,Magnetic resonance ,Bile ducts ,Prognosis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Magnetic resonance cholangiopancreatography (MRCP) is used for the diagnosis and follow-up of individuals with primary sclerosing cholangitis (PSC). The aim of our study is to develop an MRCP-score based on cholangiographic findings previously associated with outcomes and assess its reproducibility and prognostic value in PSC. Methods: The score (DiStrict score) was developed based on the extent and severity of cholangiographic changes of intrahepatic and extrahepatic bile ducts (range 0–8) on 3D-MRCP. In this retrospective, multicentre study, three pairs of radiologists with different levels of expertise from three tertiary centres applied the score independently. MRCP examinations of 220 consecutive individuals with PSC from a prospectively collected PSC-cohort, with median follow-up of 7.4 years, were reviewed. Inter-reader and intrareader agreements were assessed via intraclass correlation coefficient (ICC). After consensus, the prognostic value of the score was assessed using Cox-regression and outcome-free survival rates were assessed via Kaplan-Meier estimates. Harrell's C-statistic was calculated. Results: Forty patients developed outcomes (liver transplantation or liver-related death). Inter-reader agreement between experienced radiologists was good (ICC 0.82; 95% CI 0.74–0.87, and ICC 0.81; 95% CI 0.70–0.87, respectively) and better than the agreement for the pair of experienced/less-experienced radiologists (ICC 0.48; 95% CI 0.05–0.72). Agreement between radiologists from the three centres was good (ICC 0.76; 95% CI 0.57–0.89). Intrareader agreement was good to excellent (ICC 0.85–0.93). Harrell's C was 0.78. Patients with a DiStrict score of 5–8 had 8.2-fold higher risk (hazard ratio 8.2; 95% CI 2.97–22.65) of developing outcomes, and significantly worse survival (p
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- 2022
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8. Suppression of bile acid synthesis as a tipping point in the disease course of primary sclerosing cholangitis
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Peder Rustøen Braadland, Kai Markus Schneider, Annika Bergquist, Antonio Molinaro, Anita Lövgren-Sandblom, Marcus Henricsson, Tom Hemming Karlsen, Mette Vesterhus, Christian Trautwein, Johannes Roksund Hov, and Hanns-Ulrich Marschall
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Cholestasis ,Ursodeoxycholic acid ,Liver transplantation ,Liver transplantation-free survival ,Cholestatic liver disease ,7α-Hydroxy-4-cholesten-3-one ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Farnesoid X receptor (FXR) agonists and fibroblast growth factor 19 (FGF19) analogues suppress bile acid synthesis and are being investigated for their potential therapeutic efficacy in cholestatic liver diseases. We investigated whether bile acid synthesis associated with outcomes in 2 independent populations of people with primary sclerosing cholangitis (PSC) not receiving such therapy. Methods: Concentrations of individual bile acids and 7α-hydroxy-4-cholesten-3-one (C4) were measured in blood samples from 330 patients with PSC attending tertiary care hospitals in the discovery and validation cohorts and from 100 healthy donors. We used a predefined multivariable Cox proportional hazards model to evaluate the prognostic value of C4 to predict liver transplantation-free survival and evaluated its performance in the validation cohort. Results: The bile acid synthesis marker C4 was negatively associated with total bile acids. Patients with fully suppressed bile acid synthesis had strongly elevated total bile acids and short liver transplantation-free survival. In multivariable models, a 50% reduction in C4 corresponded to increased hazards for liver transplantation or death in both the discovery (adjusted hazard ratio [HR] = 1.24, 95% CI 1.06–1.43) and validation (adjusted HR = 1.23, 95% CI 1.03–1.47) cohorts. Adding C4 to established risk scores added value to predict future events, and predicted survival probabilities were well calibrated externally. There was no discernible impact of ursodeoxycholic acid treatment on bile acid synthesis. Conclusions: Bile acid accumulation-associated suppression of bile acid synthesis was apparent in patients with advanced PSC and associated with reduced transplantation-free survival. In a subset of the patients, bile acid synthesis was likely suppressed beyond a tipping point at which any further pharmacological suppression may be futile. Implications for patient stratification and inclusion criteria for clinical trials in PSC warrant further investigation. Lay summary: We show, by measuring the level of the metabolite C4 in the blood from patients with primary sclerosing cholangitis (PSC), that low production of bile acids in the liver predicts a more rapid progression to severe disease. Many people with PSC appear to have fully suppressed bile acid production, and both established and new drugs that aim to reduce bile acid production may therefore be futile for them. We propose C4 as a test to find those likely to respond to these treatments.
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- 2022
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9. Diagnostic yield of endomicroscopy for dysplasia in primary sclerosing cholangitis associated inflammatory bowel disease: a feasibility study
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Aldona Dlugosz, Ammar Mohkles Barakat, Niklas K. Björkström, Åke Öst, and Annika Bergquist
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and study aims: Primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD) is characterized by a high risk of colorectal dysplasia. Surveillance colonoscopies with random biopsies have doubtful power for dysplasia detection. Our aim was to prospectively investigate the feasibility and efficacy of pCLE in surveillance colonoscopies in patients with PSC-IBD. Patients and methods: Sixty-nine patients with PSC-IBD underwent colonoscopy in 2 steps. On the way from rectum to cecum, the mucosa was inspected with high definition endoscopy (HDE) and random biopsies were taken according to the standard routine. On the way from cecum to rectum, fluorescein-enhanced pCLE and chromoendoscopy were performed. Regions where random biopsies had been taken, as well as visible lesions, were examined with pCLE and targeted biopsies were taken of lesions suspicious for dysplasia. Two investigators, blinded to histology and endoscopy results, analyzed all pCLE videos off-line. Results: Nineteen biopsies obtained in 13 patients (17 targeted biopsies, 2 random biopsies) revealed the presence of low-grade dysplasia. Thirteen lesions with dysplasia were endoscopically visible but by using pCLE-targeted biopsies, additional endoscopically invisible dysplasias in 4 biopsies obtained from 3 patients were detected. The sensitivity, specificity, and accuracy of pCLE in predicting dysplasia were respectively 89 % (95 % CI: 65 – 98), 96 % (95 % CI: 94 – 97), and 96 % (95 % CI: 94 – 97). pCLE showed a good performance for differentiating neoplastic from non-neoplastic mucosa with negative predictive value of 99 %. Conclusions: pCLE in PSC-IBD surveillance is feasible and may be a good complement to HDE. Future research should aim at elucidating whether real-time pCLE is applicable in PSC-IBD surveillance.
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- 2016
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10. Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population.
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Sigrid Næss, Benedicte A Lie, Espen Melum, Marita Olsson, Johannes R Hov, Peter J P Croucher, Jochen Hampe, Erik Thorsby, Annika Bergquist, James A Traherne, Erik Schrumpf, Kirsten Muri Boberg, Stefan Schreiber, Andre Franke, and Tom H Karlsen
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Medicine ,Science - Abstract
BackgroundGenetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.Methodology/principal findingsA total of 365 PSC cases and 368 healthy controls of Scandinavian ancestry were included in the study. We incorporated data from HLA typing (HLA-A, -B, -C, -DRB3, -DRB1, -DQB1) and single nucleotide polymorphisms across the MHC (n = 18,644; genotyped and imputed) alongside previously suggested PSC risk determinants in the MHC, i.e. amino acid variation of DRβ, a MICA microsatellite polymorphism and HLA-C and HLA-B according to their ligand properties for killer immunoglobulin-like receptors. Breakdowns of the association signal by unconditional and conditional logistic regression analyses demarcated multiple PSC associated MHC haplotypes, and for eight of these classical HLA class I and II alleles represented the strongest association. A novel independent risk locus was detected near NOTCH4 in the HLA class III region, tagged by rs116212904 (odds ratio [95% confidence interval] = 2.32 [1.80, 3.00], P = 1.35×10-11).Conclusions/significanceOur study shows that classical HLA class I and II alleles, predominantly at HLA-B and HLA-DRB1, are the main risk factors for PSC in the MHC. In addition, the present assessments demonstrated for the first time an association near NOTCH4 in the HLA class III region.
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- 2014
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11. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.
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Lena Berglin, Annika Bergquist, Helene Johansson, Hans Glaumann, Carl Jorns, Sebastian Lunemann, Heiner Wedemeyer, Ewa C Ellis, and Niklas K Björkström
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Medicine ,Science - Abstract
Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.
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- 2014
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12. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis.
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Johannes R Hov, Verena Keitel, Jon K Laerdahl, Lina Spomer, Eva Ellinghaus, Abdou ElSharawy, Espen Melum, Kirsten M Boberg, Thomas Manke, Tobias Balschun, Christoph Schramm, Annika Bergquist, Tobias Weismüller, Daniel Gotthardt, Christian Rust, Liesbet Henckaerts, Clive M Onnie, Rinse K Weersma, Martina Sterneck, Andreas Teufel, Heiko Runz, Adolf Stiehl, Cyriel Y Ponsioen, Cisca Wijmenga, Morten H Vatn, IBSEN Study Group, Pieter C F Stokkers, Severine Vermeire, Christopher G Mathew, Benedicte A Lie, Ulrich Beuers, Michael P Manns, Stefan Schreiber, Erik Schrumpf, Dieter Häussinger, Andre Franke, and Tom H Karlsen
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Medicine ,Science - Abstract
TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants.Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor model, and introduced mutated TGR5 constructs into human epithelial cell lines. By using confocal microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X) were found to reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and UC associated locus at chromosome 2q35 in large patient panels revealed an overall association between the TGR5 single-nucleotide polymorphism rs11554825 and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010) and UC (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7)), but strong linkage disequilibrium precluded demarcation of TGR5 from neighboring genes.Resequencing of TGR5 along with functional investigations of novel variants provided unique insight into an important candidate gene for several inflammatory and metabolic conditions. While significant TGR5 associations were detected in both UC and PSC, further studies are needed to conclusively define the role of TGR5 variation in these diseases.
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- 2010
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13. EASL Clinical Practice Guidelines on sclerosing cholangitis
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Olivier Chazouilleres, Ulrich Beuers, Annika Bergquist, Tom Hemming Karlsen, Cynthia Levy, Marianne Samyn, Christoph Schramm, Michael Trauner, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Adult ,Hepatology ,Cholangitis, Sclerosing ,Humans ,Child ,Prognosis - Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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- 2022
14. Increased risk of cancer in patients with primary sclerosing cholangitis
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Erik von Seth, Anna Warnqvist, Annika Bergquist, Aiva Lundberg Båve, Caroline Nordenvall, and Matteo Bottai
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Crohn’s disease ,medicine.medical_specialty ,Lymphoma ,Colorectal cancer ,Epidemiology ,National register ,Population ,Cholangitis, Sclerosing ,Lower risk ,Gastroenterology ,Inflammatory bowel disease ,Primary sclerosing cholangitis ,Cohort Studies ,Risk Factors ,Pancreatic cancer ,Internal medicine ,Neoplasms ,medicine ,Humans ,education ,Crohn's disease ,education.field_of_study ,Hepatology ,business.industry ,digestive, oral, and skin physiology ,Cancer ,Hepatobiliary cancer ,medicine.disease ,Inflammatory Bowel Diseases ,Ulcerative colitis ,Matched cohort ,Original Article ,business - Abstract
Background and aims Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and colorectal cancer, but the risks of other cancer forms have not been explored. The aim of this study was to evaluate the risk of intestinal and extraintestinal cancers in a large, well-defined cohort of PSC patients. Material and method A matched cohort study of Swedish PSC patients was performed with up to ten comparators for each patient, matched for sex, age, and residency. The data were retrieved from national registers. Patients were followed from PSC diagnosis until cancer diagnosis, liver transplantation, first emigration date, death, or December 31, 2016. The risk of cancer was estimated using the Kaplan–Meier method and Cox regression models. Results In total, 1432 PSC patients with a verified diagnosis and 14,437 comparators were studied. The mean follow-up time was 15.9 years. Eighty-eight percent of the PSC patients had concomitant inflammatory bowel disease. PSC patients ran significantly increased risks of developing any cancer [HR 3.8, 95% confidence interval (CI) 3.3–4.3], hepatobiliary cancer (HR 120.9, 95% CI 72.0–203.1), colorectal cancer (HR 7.5, 95% CI 5.6–10.0), pancreatic cancer (HR 8.0, 95% CI 3.2–20.2), gastric cancer (HR 4.2, 95% CI 1.5–11.3), small bowel cancer (HR 21.1, 95% CI 3.5–128.2), and lymphoma (HR 3.0, 95% CI 1.6–5.7). PSC was not associated with a lower risk of any cancer form. Conclusions PSC patients have a four times overall increased risk of developing cancer compared to the general population, with increased risk of developing hepatobiliary, colorectal, and pancreatic cancer, as well as lymphoma.
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- 2021
15. Reply: Insurance should cover vancomycin for primary sclerosing cholangitis
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Christopher L. Bowlus, Lionel Arrivé, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Gonzalo Sapisochin, Rachna Shroff, James H. Tabibian, and David N. Assis
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Hepatology - Published
- 2023
16. Reply: Living donor liver transplantation for people with PSC
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Lisa M. Forman, Gonzalo Sapisochin, David N. Assis, Lionel Arrivé, Annika Bergquist, Christopher L. Bowlus, Mark Deneau, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Rachna Shroff, and James H. Tabibian
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Hepatology - Published
- 2023
17. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma
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Christopher L. Bowlus, Lionel Arrivé, Annika Bergquist, Mark Deneau, Lisa Forman, Sumera I. Ilyas, Keri E. Lunsford, Mercedes Martinez, Gonzalo Sapisochin, Rachna Shroff, James H. Tabibian, and David N. Assis
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Hepatology - Published
- 2022
18. Associations of neopterin and kynurenine–tryptophan ratio with survival in primary sclerosing cholangitis
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Christian Rupp, Per Magne Ueland, Annika Bergquist, Trine Folseraas, Johannes R. Hov, Amandeep Kaur Dhillon, Marius Trøseid, Øivind Midttun, Mette Vesterhus, Tom H. Karlsen, Robert Voitl, and Martin Kummen
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medicine.medical_specialty ,Cholangitis, Sclerosing ,Inflammation ,Neopterin ,Gastroenterology ,Primary sclerosing cholangitis ,Pathogenesis ,Biliary disease ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,immune system diseases ,Internal medicine ,medicine ,Humans ,Kynurenine ,Framingham Risk Score ,business.industry ,digestive, oral, and skin physiology ,Tryptophan ,medicine.disease ,Cross-Sectional Studies ,chemistry ,Cohort ,medicine.symptom ,business ,Biomarkers ,Chromatography, Liquid - Abstract
Background and aims Biomarkers of inflammation may be of clinical utility in primary sclerosing cholangitis (PSC). We aimed to investigate the interferon gamma-related biomarkers neopterin and kynurenine–tryptophanratio (KT-ratio) in PSC. Methods Circulating neopterin, tryptophan and kynurenine were measured with LC-MS/MS in multiple cross-sectional cohorts comprising in total of 524 PSC patients and 100 healthy controls from Norway, Germany and Sweden. Results Neopterin and KT-ratio were significantly increased in PSC patients compared with controls in both a discovery and a validation cohort from Norway. Furthermore, high neopterin and KT-ratio levels were associated with a shorter transplantation-free survival in the PSC patients in the Norwegian discovery cohort and the German validation cohort. However, in the validation PSC cohort from Sweden, no relationship between neopterin and KT-ratio and liver transplantation-free survival was observed. The correlations between neopterin and KT-ratio were moderate to strong and similar in all cohorts (rho 0.50–0.67). Neopterin and KT-ratio also correlated with C-reactive protein (rho 0.17-0.63) and revised Mayo risk score (rho 0.23–0.42) in all cohorts. Conclusions Neopterin and KT-ratio were elevated in PSC and associated with liver transplantation-free survival in two independent PSC cohorts, highlighting a possible role of interferon gamma-driven inflammation in the pathogenesis. However, the lack of association with survival in one of the cohorts reduces the potential clinical value of neopterin and KT-ratioas biomarkers and highlights the need to validate new biomarkers in PSC in multiple cohorts. publishedVersion
- Published
- 2021
19. Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile
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Tom H. Karlsen, Guro Elisabeth Lind, Hege Marie Vedeld, Erik von Seth, Vemund Paulsen, Martti Färkkilä, Kim Andresen, Hilde Honne, Heidi D. Pharo, Kirsten Muri Boberg, Annika Bergquist, Marine Jeanmougin, Marit Mæhle Grimsrud, Trine Folseraas, Lars Aabakken, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, University of Helsinki, and Gastroenterologian yksikkö
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Male ,medicine.medical_specialty ,endocrine system diseases ,Cholangitis, Sclerosing ,Malignancy ,DIAGNOSIS ,Gastroenterology ,Polymerase Chain Reaction ,digestive system ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,parasitic diseases ,SURVEILLANCE ,medicine ,Biomarkers, Tumor ,Bile ,Humans ,Digital polymerase chain reaction ,In patient ,CYTOLOGY RISK-FACTORS ,DYSPLASIA ,Early Detection of Cancer ,Neoplasm Staging ,Hepatology ,Receiver operating characteristic ,business.industry ,fungi ,digestive, oral, and skin physiology ,BRUSH CYTOLOGY ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Bile Duct Neoplasms ,ROC Curve ,Dysplasia ,030220 oncology & carcinogenesis ,3121 General medicine, internal medicine and other clinical medicine ,DNA methylation ,030211 gastroenterology & hepatology ,Female ,business ,BILIARY CYTOLOGY ,Follow-Up Studies - Abstract
Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77–0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow-up (> 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSC ≤ 12 patients, all positive for the biomarkers, included both early-stage and late-stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19-9 levels. Conclusions Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.
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- 2022
20. Outcome after resection for perihilar cholangiocarcinoma in patients with primary sclerosing cholangitis: an international multicentre study
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F. Bartsch, J. Hagendoorn, R. Charco, Q.I. Molenaar, Hauke Lang, A. Sultana, F. Heid, J.I. Erdmann, Erik Schadde, G. Kazemier, H.Z. Malik, J. Rolinger, Stefan Buettner, C.L.M. Nota, Andrea Ruzzenente, M.C. Giglio, Mikhail Efanov, Shishir K. Maithel, P. Muiesan, M. Ravaioli, K.J. Roberts, I. Capobianco, Thomas M. van Gulik, J. van Vugt, Ruslan Alikhanov, Hannes Jansson, A. Andreou, Alfredo Guglielmi, Johann Pratschke, M. Malago, Moritz Schmelzle, E. de Savornin Lohman, Silvio Nadalin, Marjolein A P Ligthart, P.R. de Reuver, Bas Groot Koerkamp, S. W. M. Olde Damink, L.E. Nooijen, Francesca Ratti, S. van Laarhoven, C. Gomez-Gavara, B.M. Zonderhuis, C. Benzing, Matteo Serenari, Luca Aldrighetti, L.C. Franken, Annika Bergquist, Cornelis H. C. Dejong, Ernesto Sparrelid, Matteo Cescon, William R. Jarnagin, L.M. Quinn, Pim B. Olthof, J.N.M. IJzermans, Roberto Troisi, RS: NUTRIM - R2 - Liver and digestive health, Surgery, MUMC+: MA Heelkunde (9), Jansson, H., Olthof, P. B., Bergquist, A., Ligthart, M. A. P., Nadalin, S., Troisi, R, Groot Koerkamp, B., Alikhanov, R., Lang, H., Guglielmi, A., Cescon, M., Jarnagin, W. R., Aldrighetti, L., van Gulik, T. M., Sparrelid, E., Andreou, A., Bartsch, F., Benzing, C., Buettner, S., Capobianco, I., Charco, R., de Reuver, P. R., de Savornin Lohman, E., Dejong, C. H. C., Efanov, M., Erdmann, J. I., Franken, L. C., Giglio, M. C., Gomez-Gavara, C., Hagendoorn, J., Heid, F., Ijzermans, J. N. M., Kazemier, G., Maithel, S. K., Malago, M., Malik, H. Z., Molenaar, Q. I., Muiesan, P., Nooijen, L. E., Nota, C. L. M., Olde Damink, S. W. M., Pratschke, J., Quinn, L. M., Ratti, F., Ravaioli, M., Roberts, K. J., Rolinger, J., Ruzzenente, A., Schadde, E., Schmelzle, M., Serenari, M., Sultana, A., van Laarhoven, S., van Vugt, J. L. A., Zonderhuis, B. M., Troisi, R. I., CCA - Cancer Treatment and Quality of Life, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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medicine.medical_specialty ,endocrine system diseases ,Cholangitis ,Cholangitis, Sclerosing ,030230 surgery ,HILAR CHOLANGIOCARCINOMA ,Gastroenterology ,digestive system ,Article ,Sclerosing ,Resection ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,03 medical and health sciences ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Primary outcome ,Internal medicine ,Overall survival ,medicine ,Humans ,In patient ,Perihilar Cholangiocarcinoma ,Retrospective Studies ,Intrahepatic ,RISK ,Hepatology ,business.industry ,digestive, oral, and skin physiology ,Retrospective cohort study ,medicine.disease ,digestive system diseases ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Postoperative mortality ,030220 oncology & carcinogenesis ,Bile Ducts ,business ,Klatskin Tumor - Abstract
Contains fulltext : 245473.pdf (Publisher’s version ) (Open Access) BACKGROUND: Resection for perihilar cholangiocarcinoma (pCCA) in primary sclerosing cholangitis (PSC) has been reported to lead to worse outcomes than resection for non-PSC pCCA. The aim of this study was to compare prognostic factors and outcomes after resection in patients with PSC-associated pCCA and non-PSC pCCA. METHODS: The international retrospective cohort comprised patients resected for pCCA from 21 centres (2000-2020). Patients operated with hepatobiliary resection, with pCCA verified by histology and with data on PSC status, were included. The primary outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. RESULTS: Of 1128 pCCA patients, 34 (3.0%) had underlying PSC. Median overall survival after resection was 33 months for PSC patients and 29 months for non-PSC patients (p = .630). Complications (Clavien-Dindo grade ≥ 3) were more frequent in PSC pCCA (71% versus 44%, p = .003). The rate of posthepatectomy liver failure (21% versus 17%, p = .530) and 90-day mortality (12% versus 13%, p = 1.000) was similar for PSC and non-PSC patients. CONCLUSION: Median overall survival after resection for pCCA was similar in patients with underlying PSC and non-PSC patients. Complications were more frequent after resection for PSC-associated pCCA, with no difference in postoperative mortality.
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- 2021
21. Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma
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Dan Sun, Joana Dias, Helene Johansson, Martin Cornillet, Hans Glaumann, Otto Strauss, Hannes Jansson, Jesper B. Andersen, Colm J O'Rourke, Erik von Seth, Lena Berglin, Johan K. Sandberg, Espen Melum, Ernesto Sparrelid, Niklas K. Björkström, Iva Filipovic, Christine L. Zimmer, Ewa Ellis, Laura Hertwig, and Annika Bergquist
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Tumor microenvironment ,education.field_of_study ,Hepatology ,medicine.diagnostic_test ,medicine.medical_treatment ,Cell ,Population ,Immunotherapy ,Biology ,Mucosal-Associated Invariant T Cells ,Flow cytometry ,Cholangiocarcinoma ,medicine.anatomical_structure ,Immune system ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Bile Ducts, Extrahepatic ,medicine ,Cancer research ,Tumor Microenvironment ,Immunohistochemistry ,Cytotoxic T cell ,Humans ,education - Abstract
Background and Aims: Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). Approach and Results: Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. Conclusions: MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.
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- 2021
22. A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
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Johannes R. Hov, Marcus Buggert, Laura Hertwig, Jeff E. Mold, Otto Strauss, Kristian Holm, Jakob Michaëlsson, Marcus Reuterwall Hansson, Erik von Seth, Christine L. Zimmer, Åsa V. Keita, Son Nguyen, Annika Bergquist, Martin Cornillet, Alicia Y W Wong, Ewa Ellis, Andrea Ponzetta, Chiara Zotter, Niklas K. Björkström, Johan D. Söderholm, Volkan Özenci, Lena Berglin, Ernesto Sparrelid, and Urban Arnelo
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Neutrophils ,T-Lymphocytes ,digestive, oral, and skin physiology ,Cholangitis, Sclerosing ,Inflammation ,General Medicine ,Biology ,medicine.disease ,digestive system ,Primary sclerosing cholangitis ,Immune system ,Liver ,Biliary tract ,Immunology ,medicine ,Humans ,Interleukin 8 ,medicine.symptom ,Biliary Tract ,Infiltration (medical) ,CXCL16 ,Homing (hematopoietic) - Abstract
The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103+CD69+ effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.
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- 2021
23. Assessment of prognostic value and interreader agreement of ANALI scores in patients with primary sclerosing cholangitis
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Mats Andersson, Nikolaos Kartalis, Kristina Ringe, Annika Bergquist, and Aristeidis Grigoriadis
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medicine.medical_specialty ,education.field_of_study ,medicine.diagnostic_test ,Proportional hazards model ,Intraclass correlation ,business.industry ,Hazard ratio ,Population ,Cholangitis, Sclerosing ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Prognosis ,Magnetic Resonance Imaging ,Primary sclerosing cholangitis ,Transplantation ,Hypertension, Portal ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Decompensation ,Radiology ,Prospective Studies ,education ,business - Abstract
Purpose ANALI-scores are two prognostic magnetic resonance imaging (MRI)-based scores developed for patients with primary sclerosing cholangitis (PSC). Our study aims to assess the interreader agreement between expert radiologists of the two ANALI-scores and of the radiological parameters they utilize, and to test the prognostic performance of the scores in our population. Method Three radiologists evaluated MRIs of 98 PSC-patients from a prospectively collected cohort with median follow-up of 6.7 years. Each parameter of ANALI-scores was assessed, and the scores were calculated. Interreader agreement was assessed with intraclass correlation coefficient (ICC). After consensus reading was reached, the prognostic value of ANALI-scores was assessed with Cox regression, and outcome-free survival rates were evaluated with Kaplan-Meier estimates. Results The ANALI-score without gadolinium had poor to moderate (ICC = 0.56, 95 %CI: 0.42–0.68) and with gadolinium poor (ICC = 0.30, 95 %CI: 0.16–0.44) agreement. Liver deformity (ICC = 0.28, 95 %CI: 0.13–0.44) and parenchymal enhancement heterogeneity (ICC = 0.24, 95 %CI: 0.12–0.38) had poor agreement. Portal hypertension had poor to moderate (ICC = 0.48, 95 %CI: 0.36–0.59) and dilatation of the intrahepatic ducts had moderate (ICC = 0.64, 95 %CI: 0.54–0.73) agreement. Hazard ratios for liver-related death, transplantation or cirrhosis decompensation of the ANALI-scores with and without gadolinium were 3.53 (95 %CI: 1.40–8.93) and 2.25 (95 %CI: 1.56–3.24), respectively. Outcome-free survival was better for patients with low ANALI-scores. Conclusions The ANALI-scores show poor to moderate agreement, which challenges their usefulness in clinical practice. They are associated with clinical outcomes, confirming the value of imaging in prognosis of PSC, but need further multicenter evaluation.
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- 2021
24. Development of a novel MRCP-score for patients with primary sclerosing cholangitis, and assessment of agreement and prognostic value
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Aristeidis Grigoriadis, Kristina Ringe, Johan Bengtsson, Erik Fridh Baubeta, Cecilia Forsman, Nafsika Korsavidou-Hult, Fredrik Rorsman, Emma Nilsson, Nikolaos Kartalis, and Annika Bergquist
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Hepatology - Published
- 2022
25. Cholangiocytes cleave surface CD100 from biliary infiltrating T cells and mediate pathogenic Th17 differentiation
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Xiaojun Jiang, Kari Otterdal, Brian K. Chung, Christopher Maucourant, Christine Zimmer, Sverre Holm, Daniel Geanon, Annika Bergquist, Tom Hemming Karlsen, Niklas Björkström, and Espen Melum
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Hepatology - Published
- 2022
26. Sa1438: TIME TO CHOLANGIOCARCINOMA IN PEDIATRIC ONSET PSC-IBD
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Batul Kaj-Carbaidwala, Johan M. Fevery, Douglas G. Adler, Annika Bergquist, Lissy De Ridder, Mark R. Deneau, Corinne Gower, Roger W. Chapman, Kate D. Lynch, Catherine A. Stedman, David Wilson, Uzma Shah, Harland S. Winter, and Jochen K. Lennerz
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Hepatology ,Gastroenterology - Published
- 2022
27. A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis
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Kjetil Taskén, Kimia T. Maleki, Sigrid S. Skånland, Jon K. Laerdahl, Andre Franke, Britt-Sabina Löscher, Espen Melum, Annika Bergquist, Tom H. Karlsen, Martin Cornillet, Niklas K. Björkström, Xiaojun Jiang, Kristian Holm, Geetha Venkatesh, and Jeff E. Mold
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0301 basic medicine ,T-Lymphocytes ,T cell ,Cholangitis, Sclerosing ,Semaphorins ,Biology ,medicine.disease_cause ,Germline ,Primary sclerosing cholangitis ,Pathogenesis ,Interferon-gamma ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Interferon ,medicine ,Homologous chromosome ,Animals ,Missense mutation ,Gene Knock-In Techniques ,Germ-Line Mutation ,Mutation ,General Medicine ,medicine.disease ,Germ Cells ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,medicine.drug - Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease without clear etiology or effective treatment. Genetic factors contribute to PSC pathogenesis, but so far, no causative mutation has been found. We performed whole-exome sequencing in a family with autosomal dominant inheritance of PSC and identified a heterozygous germline missense mutation in SEMA4D, encoding a K849T variant of CD100. The mutation was located in an evolutionarily conserved, unstructured cytosolic region of CD100 affecting downstream signaling. It was found to alter the function of CD100-expressing cells with a bias toward the T cell compartment that caused increased proliferation and impaired interferon-γ (IFN-γ) production after stimulation. Homologous mutation knock-in mice developed similar IFN-γ impairment in T cells and were more prone to develop severe cholangitis when exposed to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Transfer of wild-type T cells to knock-in mice before and during DDC exposure attenuated cholangitis. Taken together, we identified an inherited mutation in the disordered cytosolic region of CD100 resulting in T cell functional defects. Our findings suggest a protective role for T cells in PSC that might be used therapeutically.
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- 2021
28. Neoplastic risk for liver and colon in primary sclerosing cholangitis
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Annika Bergquist and Aiva Lundberg Båve
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medicine.medical_specialty ,business.industry ,medicine.disease ,Hepatobiliary cancer ,Inflammatory bowel disease ,Gastroenterology ,Primary sclerosing cholangitis ,Hepatocellular carcinoma ,Pancreatic cancer ,Internal medicine ,Epidemiology ,medicine ,Gallbladder cancer ,business - Published
- 2021
29. Percutaneous transhepatic cholangiodrainage in patients with PSC: a multicentre, retrospective analysis
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T Zhou, Samuel Huber, Hanno Ehlken, Tobias J. Weismüller, T Rösch, AW Lohse, Annika Bergquist, M Wiestler, C Villard, Marcial Sebode, and G Buescher
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medicine.medical_specialty ,business.industry ,Retrospective analysis ,Medicine ,In patient ,business ,Percutaneous transhepatic cholangiodrainage ,Surgery - Published
- 2021
30. Malmö in Time and Space.
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Annika Bergquist and Lena Wilhelmsson
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- 1993
31. Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities
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Stephanie Roessler, Martti Färkkilä, Daniel Gotthardt, Ivo Buchhalter, Arndt Vogel, Johanna Arola, Krzysztof Grzyb, Cyriel Y. Ponsioen, Gideon M. Hirschfield, Arianeb Mehrabi, Christoph Schramm, Anna-Lena Volckmar, Joanne Verheij, Trine Folseraas, Gary M. Reynolds, Annika Bergquist, Albrecht Stenzinger, Sören Weidemann, Angela Cheung, Erik von Seth, Andre Franke, Matthias Kloor, Heikki Mäkisalo, Giuseppe Mazza, Piotr Milkiewicz, Kirsten Muri Boberg, John C. Cheville, Tor J. Eide, Volker Endris, Tom H. Karlsen, Benjamin Goeppert, Barbara Górnicka, Peter Schirmacher, Marit Mæhle Grimsrud, Michael P. Manns, Konstantinos N. Lazaridis, Pathology, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, HUSLAB, Department of Pathology, Helsinki University Hospital Area, HUS Abdominal Center, IV kirurgian klinikka, Centre of Excellence in Complex Disease Genetics, Department of Medicine, Clinicum, and Gastroenterologian yksikkö
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Cholangitis, Sclerosing ,medicine.disease_cause ,digestive system ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,Proto-Oncogene Proteins p21(ras) ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,medicine ,Humans ,Copy-number variation ,Child ,Pathological ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Cause of death ,RISK ,RECEPTOR ,Hepatology ,MUTATIONS ,business.industry ,digestive, oral, and skin physiology ,Genomics ,Middle Aged ,Genes, p53 ,medicine.disease ,Phenotype ,digestive system diseases ,3. Good health ,030104 developmental biology ,Bile Duct Neoplasms ,3121 General medicine, internal medicine and other clinical medicine ,Mutation ,PATTERNS ,Immunohistochemistry ,Female ,030211 gastroenterology & hepatology ,KRAS ,business - Abstract
Background and Aims Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). Approach and Results We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 patients with PSC-BTC from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations, and copy number variations, along with histomorphological and immunohistochemical characterization. Regardless of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, such asTP53(35.5%),KRAS(28.0%),CDKN2A(14.5%), andSMAD4(11.3%), as well as potentially druggable mutations (e.g.,HER2/ERBB2). We found a high frequency of nontypical/nonductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%). Conclusions Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC shows a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.
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- 2020
32. Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up magnetic resonance imaging/3D magnetic resonance cholangiopancreatography of patients with primary sclerosing cholangitis
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Nikolaos Kartalis, Fabian Morsbach, Aristeidis Grigoriadis, Annika Bergquist, Karouk Said, and Nikolaos Voulgarakis
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cholangiopancreatography, Magnetic Resonance ,Cholangitis, Sclerosing ,Constriction, Pathologic ,Primary sclerosing cholangitis ,Interpretation (model theory) ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Imaging, Three-Dimensional ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Expert Testimony ,Aged ,Cholangiopancreatography, Endoscopic Retrograde ,Magnetic resonance cholangiopancreatography ,medicine.diagnostic_test ,Bile duct ,business.industry ,Gastroenterology ,Reproducibility of Results ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Radiological weapon ,030211 gastroenterology & hepatology ,Female ,Radiology ,Bile Ducts ,Clinical Competence ,business - Abstract
Objectives: Interpretation of MRI/MRCP in primary sclerosing cholangitis (PSC) at a single time point has low inter-reader agreement. Agreement of interpretation of the dynamic course of du...
- Published
- 2020
33. Genomic characterization of cholangiocarcinoma in primary sclerosing cholangitis reveals novel therapeutic opportunities
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Sören Weidemann, Konstantinos N. Lazaridis, Martti Färkkilä, Daniel Gotthardt, Marit Mæhle Grimsrud, Heikki Mäkisalo, E. von Seth, Tom H. Karlsen, Stephanie Roessler, Cyriel Y. Ponsioen, Johanna Arola, Giuseppe Mazza, Gideon M. Hirschfield, Michael P. Manns, Volker Endris, K Grzyb, Angela C. Cheung, Albrecht Stenzinger, Barbara Górnicka, Christoph Schramm, Matthias Kloor, Annika Bergquist, John C. Cheville, Tor J. Eide, Ivo Buchhalter, Andre Franke, Joanne Verheij, Kirsten Muri Boberg, Arndt Vogel, Peter Schirmacher, Piotr Milkiewicz, Trine Folseraas, Benjamin Goeppert, Arianeb Mehrabi, Gary M. Reynolds, and Anna-Lena Volckmar
- Subjects
0303 health sciences ,03 medical and health sciences ,Pathology ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,medicine ,medicine.disease ,business ,030304 developmental biology ,Primary sclerosing cholangitis - Published
- 2020
34. Outcome after Resection for Perihilar Cholangiocarcinoma in Primary Sclerosing Cholangitis - an International Multicenter Study from the Perihilar Cholangiocarcinoma Collaboration Group
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P.B. Olthof, T.M. van Gulik, Annika Bergquist, Ernesto Sparrelid, and Hannes Jansson
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medicine.medical_specialty ,Hepatology ,Multicenter study ,business.industry ,Gastroenterology ,medicine ,Radiology ,Perihilar Cholangiocarcinoma ,medicine.disease ,business ,Primary sclerosing cholangitis ,Resection - Published
- 2021
35. Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients
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E. von Seth, Annika Bergquist, Caroline Nordenvall, Per Nilsson, Ola Olén, Anders Ekbom, Pär Myrelid, and Matteo Bottai
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medicine.medical_specialty ,endocrine system diseases ,Hepatology ,business.industry ,medicine.medical_treatment ,digestive, oral, and skin physiology ,Gastroenterology ,medicine.disease ,digestive system ,Inflammatory bowel disease ,digestive system diseases ,Primary sclerosing cholangitis ,03 medical and health sciences ,0302 clinical medicine ,Close relationship ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Pharmacology (medical) ,business ,Colectomy ,Cohort study - Abstract
Background: Despite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains cont ...
- Published
- 2017
36. Optimizing the detection of biliary dysplasia in primary sclerosing cholangitis before liver transplantation
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Maria Castedal, Karouk Said, Ammar Majeed, Urban Arnelo, Gunnar Söderdahl, and Annika Bergquist
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Cholangitis, Sclerosing ,Bile Duct Neoplasm ,Liver transplantation ,Sensitivity and Specificity ,digestive system ,Gastroenterology ,Primary sclerosing cholangitis ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Metaplasia ,Internal medicine ,medicine ,Humans ,In Situ Hybridization, Fluorescence ,Cholangiopancreatography, Endoscopic Retrograde ,Sweden ,medicine.diagnostic_test ,business.industry ,Biliary Dysplasia ,Middle Aged ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Dysplasia ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Histopathology ,medicine.symptom ,business ,Precancerous Conditions ,Fluorescence in situ hybridization - Abstract
Background: Patients with primary sclerosing cholangitis (PSC) have increased risk of cholangiocarcinoma (CCA). We evaluated pre-transplant work-up in PSC patients, to search for the most effective strategy for the detection of biliary dysplasia or early CCA. Methods: Two hundred and twenty five consecutive PSC patients undergoing liver transplantation (LTx) in Sweden between 1999 and 2013 were studied. Patients with CCA or dysplasia in the explanted liver were compared with those with benign histopathology. Measures of test performance were calculated for patients having brush cytology on one endoscopic retrograde cholangiopancreaticography (ERCP) occasion, for those having repeated examinations with or without cholangioscopy, and for fluorescence in situ hybridization (FISH). Survival after LTx was analyzed. Results: Brush cytology on a single ERCP occasion had moderate sensitivity (57%) and high specificity (94%) for the detection of CCA/high grade dysplasia (HGD) in the explanted liver. The corresponding sensitivity and specificity for FISH were 84% and 90%, respectively. Utilizing repeated ERCP and brush cytology to confirm the initial finding improved sensitivity to 82%. Using single operator cholangioscopy (SOC) for targeted examination at the second ERCP improved sensitivity (100%) and specificity (97%) significantly. Mortality rate in patients with incidentally discovered CCA (n = 16) in the explanted liver was significantly higher than in patients with HGD or benign histopathology (HR 16.0; 95% CI, 5.6–45.4; p Conclusions: Repeated brush cytology especially when combined with targeted examination under SOC guidance is superior to single brush examinations. This strategy improves the detection of malignancy in PSC and is of importance for selection of patients for LTx.
- Published
- 2017
37. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
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Martina Sterneck, Wolfgang Lieb, Christian Rust, Tom H. Karlsen, Massimo Pinzani, Erik Schrumpf, John E. Eaton, Gideon M. Hirschfield, Christoph Schramm, Richard Sandford, Ulrich Beuers, Andrew Mason, Espen Melum, Daniel Gotthardt, A. Boudewijn de Vries, I. Franceschet, Konstantinos N. Lazaridis, Floris Imhann, Marco Carbone, Pietro Invernizzi, Mark S. Silverberg, Simon Hohenester, Maria Consiglia Bragazzi, Andreas Teufel, Bart van Hoek, Martti Färkkilä, Einar Bjornsson, Cyriel Y. Ponsioen, Brijesh Srivastava, Joanne Verheij, Roger W. Chapman, Krista Rombouts, Niklas K. Björkström, Johannes R. Hov, Weiwei Wang, F. Sampaziotis, Ludovic Vallier, Albert Parés, Eleonora A. M. Festen, Kristian Holm, Kalliopi Zachou, Katrin Böttcher, Christopher L. Bowlus, Xiaojun Jiang, Trine Folseraas, Elisabeth M.G. de Vries, Simon M. Rushbrook, Piotr Milkiewicz, Carl A. Anderson, Georgios N. Dalekos, David Ellinghaus, Hanns-Ulrich Marschall, Rinse K. Weersma, Marco Marzioni, Olivier Chazouillères, Domenico Alvaro, Christian Rupp, Angela M. Cheung, Jimmy Z. Liu, Brian D. Juran, Michael P. Manns, Rudi Alberts, Bertus Eksteen, Tobias J. Weismüller, Graeme J.M. Alexander, Annarosa Floreani, Tobias Müller, Stefan Schreiber, Andre Franke, Elizabeth C. Goode, Henrike Lenzen, Arnau Vich Vila, Annika Bergquist, Kirsten Muri Boberg, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Pathology, Alberts, R, De Vries, E, Goode, E, Jiang, X, Sampaziotis, F, Rombouts, K, Böttcher, K, Folseraas, T, Weismüller, T, Mason, A, Wang, W, Alexander, G, Alvaro, D, Bergquist, A, Björkström, N, Beuers, U, Björnsson, E, Boberg, K, Bowlus, C, Bragazzi, M, Carbone, M, Chazouillères, O, Cheung, A, Dalekos, G, Eaton, J, Eksteen, B, Ellinghaus, D, Färkkilä, M, Festen, E, Floreani, A, Franceschet, I, Gotthardt, D, Hirschfield, G, Hoek, B, Holm, K, Hohenester, S, Hov, J, Imhann, F, Invernizzi, P, Juran, B, Lenzen, H, Lieb, W, Liu, J, Marschall, H, Marzioni, M, Melum, E, Milkiewicz, P, Müller, T, Pares, A, Rupp, C, Rust, C, Sandford, R, Schramm, C, Schreiber, S, Schrumpf, E, Silverberg, M, Srivastava, B, Sterneck, M, Teufel, A, Vallier, L, Verheij, J, Vila, A, Vries, B, Zachou, K, Chapman, R, Manns, M, Pinzani, M, Rushbrook, S, Lazaridis, K, Franke, A, Anderson, C, Karlsen, T, Ponsioen, C, Weersma, R, Centre of Excellence in Complex Disease Genetics, Doctoral Programme in Drug Research, Department of Medicine, Clinicum, Gastroenterologian yksikkö, HUS Abdominal Center, and Universitat de Barcelona
- Subjects
Male ,0301 basic medicine ,Oncology ,Candidate gene ,Cholangitis ,medicine.medical_treatment ,Medizin ,Trasplantament hepàtic ,Genome-wide association study ,Kaplan-Meier Estimate ,LIVER FIBROSIS ,Liver transplantation ,Bioinformatics ,Sclerosing ,Oral and gastrointestinal ,Primary sclerosing cholangitis ,genetics ,liver transplantation ,Cohort Studies ,ACTIVATION ,0302 clinical medicine ,MED/12 - GASTROENTEROLOGIA ,MULTIPLE ,2.1 Biological and endogenous factors ,EPIDEMIOLOGY ,Aetiology ,CIRRHOSIS ,Bilious diseases and biliousness ,Liver Disease ,digestive, oral, and skin physiology ,Gastroenterology ,Single Nucleotide ,Primary sclerosing cholangiti ,Middle Aged ,3. Good health ,ULCERATIVE-COLITIS ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,Adult ,medicine.medical_specialty ,Cholangitis, Sclerosing ,Chronic Liver Disease and Cirrhosis ,Clinical Sciences ,Malalties del tracte biliar ,Single-nucleotide polymorphism ,HEPATIC STELLATE CELLS ,Polymorphism, Single Nucleotide ,International PSC Study Group ,Article ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,Internal medicine ,Genetics ,medicine ,Humans ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Allele ,Digestive Diseases - (Gallbladder) ,Survival analysis ,Proportional Hazards Models ,MALIGNANCY ,The UK PSC Consortium ,Transplantation ,Gastroenterology & Hepatology ,business.industry ,Proportional hazards model ,medicine.disease ,RISK LOCI ,Logistic Models ,030104 developmental biology ,3121 General medicine, internal medicine and other clinical medicine ,genetic ,Hepatic transplantation ,Thrombospondins ,Digestive Diseases ,business ,Genètica - Abstract
ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.ResultsWe identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10–9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.ConclusionWe present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
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- 2017
38. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease
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Christopher L. Bowlus, Sören Mucha, Piotr Milkiewicz, Jennifer G. Sambrook, Michael P. Manns, Peter R. Durie, Daniel J. Gaffney, Catalina Coltescu, Konstantinos N. Lazaridis, David Ellinghaus, Daniel Gotthardt, George F. Mells, Espen Melum, Joseph A. Odin, Mattias Laudes, Cisca Wijmenga, Kris V. Kowdley, Annarosa Floreani, Tejas S. Shah, Richard Sandford, Erik M. Schlicht, Kirsten Muri Boberg, Javier Gutierrez-Achury, Felix Braun, Martina Sterneck, Carl A. Anderson, Tom H. Karlsen, Andre Franke, Velimir A. Luketic, Brijesh Srivastava, Aliya Gulamhusein, Elizabeth C. Goode, Kelly Spiess, Gunnar Jacobs, Olivier Chazouillères, Wolfgang Lieb, Tobias Müller, Andreas Teufel, Trine Folseraas, Roger W. Chapman, Hanns-Ulrich Marschall, David J. Roberts, Christoph Schramm, Sun-Gou Ji, Albert Parés, Mariza de Andrade, Stefan Schreiber, Elizabeth J. Atkinson, Kimmo Kontula, Pietro Invernizzi, Simon M. Rushbrook, Luke Jostins, Carmel Moore, Naga Chalasani, Jimmy Z. Liu, Brian D. Juran, Willem H. Ouwehand, Graeme J.M. Alexander, John E. Eaton, Gideon M. Hirschfield, Natsuhiko Kumasaka, Martti Färkkilä, Annika Bergquist, Kapil B. Chopra, John Danesh, Bertus Eksteen, Tobias J. Weismüller, Rinse K. Weersma, Ulrich Beuers, Severine Vermeire, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Ji, S, Juran, B, Mucha, S, Folseraas, T, Jostins, L, Melum, E, Kumasaka, N, Atkinson, E, Schlicht, E, Liu, J, Shah, T, Gutierrez Achury, J, Boberg, K, Bergquist, A, Vermeire, S, Eksteen, B, Durie, P, Farkkila, M, Müller, T, Schramm, C, Sterneck, M, Weismüller, T, Gotthardt, D, Ellinghaus, D, Braun, F, Teufel, A, Laudes, M, Lieb, W, Jacobs, G, Beuers, U, Weersma, R, Wijmenga, C, Marschall, H, Milkiewicz, P, Pares, A, Kontula, K, Chazouillères, O, Invernizzi, P, Goode, E, Spiess, K, Moore, C, Sambrook, J, Ouwehand, W, Roberts, D, Danesh, J, Floreani, A, Gulamhusein, A, Eaton, J, Schreiber, S, Coltescu, C, Bowlus, C, Luketic, V, Odin, J, Chopra, K, Kowdley, K, Chalasani, N, Manns, M, Srivastava, B, Mells, G, Sandford, R, Alexander, G, Gaffney, D, Chapman, R, Hirschfield, G, de Andrade, M, Rushbrook, S, Franke, A, Karlsen, T, Lazaridis, K, Anderson, C, and Universitat de Barcelona
- Subjects
0301 basic medicine ,Genome-wide association study ,VARIANTS ,Bioinformatics ,Gastroenterology ,Inflammatory bowel disease ,0302 clinical medicine ,Risk Factors ,Gastroenterologia ,education.field_of_study ,digestive, oral, and skin physiology ,REGIONS ,Ulcerative colitis ,Inflamació ,3. Good health ,Malalties inflamatòries intestinals ,ULCERATIVE-COLITIS ,030211 gastroenterology & hepatology ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,Population ,Cholangitis, Sclerosing ,Locus (genetics) ,Biology ,Inflammatory bowel diseases ,digestive system ,Polymorphism, Single Nucleotide ,Article ,Primary sclerosing cholangitis ,03 medical and health sciences ,Internal medicine ,REVEALS ,Genetics ,medicine ,SNP ,Humans ,RNA, Messenger ,Allele ,TRANSCRIPTOME ,education ,METAANALYSIS ,Alleles ,Adaptor Proteins, Signal Transducing ,Inflammation ,medicine.disease ,Inflammatory Bowel Diseases ,digestive system diseases ,030104 developmental biology ,PSORIATIC-ARTHRITIS ,Colitis, Ulcerative ,Genome-Wide Association Study - Abstract
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; similar to 75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (r(G)) between PSC and ulcerative colitis (UC) (r(G) = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (r(G) = 0.04) (P = 2.55 x 10(-15)). UC and CD were genetically more similar to each other (r(G) = 0.56) than either was to PSC (P
- Published
- 2016
39. Reply
- Author
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Karin Söderberg-Löfdal, Matteo Bottai, Annika Bergquist, and Knut Stokkeland
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Drug ,medicine.medical_specialty ,Hepatology ,business.industry ,media_common.quotation_subject ,Cholangitis, Sclerosing ,Gastroenterology ,medicine.disease ,Inflammatory bowel disease ,Primary sclerosing cholangitis ,Internal medicine ,Medicine ,Humans ,In patient ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,media_common - Published
- 2019
40. Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis
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Karima Ben Belkacem, Neta Gotlieb, Severine Vermeire, Christoph Schramm, Roger W. Chapman, Nicholas Fonseca Nogueira, Emma Nilsson, Henriette Ytting, Hanns-Ulrich Marschall, João Sabino, Sven Almer, Cyriel Y. Ponsioen, Geir Larsson, Kate D. Lynch, Gina Sado, Ellina Lytvyak, Douglas Thorburn, Bjørn Moum, Olivier Chazouillères, Oren Shibolet, Kim N. van Munster, Christian Rupp, Alessandra Zago, Fredrik Rorsman, Christopher L. Bowlus, K. K. Jørgensen, Cynthia Levy, Mette Vesterhus, Alessio Gerussi, Charlotte R H Hedin, Francesca Saffioti, Aldo J. Montano-Loza, Andrew Mason, Nora Cazzagon, Annika Bergquist, Nelson Ndegwa, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Hedin, C, Sado, G, Ndegwa, N, Lytvyak, E, Mason, A, Montano-Loza, A, Gerussi, A, Saffioti, F, Thorburn, D, Nilsson, E, Larsson, G, Moum, B, van Munster, K, Ponsioen, C, Levy, C, Nogueira, N, Bowlus, C, Gotlieb, N, Shibolet, O, Lynch, K, Chapman, R, Rupp, C, Vesterhus, M, Jorgensen, K, Rorsman, F, Schramm, C, Sabino, J, Vermeire, S, Zago, A, Cazzagon, N, Marschall, H, Ytting, H, Ben Belkacem, K, Chazouilleres, O, Almer, S, and Bergquist, A
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Exacerbation ,Cholangitis, Sclerosing ,digestive system ,Inflammatory bowel disease ,Gastroenterology ,Primary sclerosing cholangitis ,Anti-Inflammatory ,03 medical and health sciences ,0302 clinical medicine ,Hepatic ,MED/12 - GASTROENTEROLOGIA ,Interquartile range ,Internal medicine ,medicine ,Adalimumab ,Humans ,Retrospective Studies ,Hepatology ,Tumor Necrosis Factor-alpha ,business.industry ,Inflammatory Bowel Diseases ,medicine.disease ,Infliximab ,digestive system diseases ,Intestine ,Liver Transplantation ,030220 oncology & carcinogenesis ,Tumor Necrosis Factor Inhibitors ,030211 gastroenterology & hepatology ,Liver function ,MED/09 - MEDICINA INTERNA ,Calprotectin ,business ,medicine.drug - Abstract
Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. Results: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P =.035). Factors associated with lower ALP were normal ALP at baseline (P
- Published
- 2020
41. Clinical features and MRI progression of small duct primary sclerosing cholangitis (PSC)
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Kristina Ringe, Aristeidis Grigoriadis, Frank Wacker, Michael P. Manns, Nikolaos Kartalis, Henrike Lenzen, and Annika Bergquist
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cholangitis, Sclerosing ,Medizin ,030218 nuclear medicine & medical imaging ,Primary sclerosing cholangitis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cholangiography ,Liver Function Tests ,medicine ,Deformity ,Humans ,Radiology, Nuclear Medicine and imaging ,Biliary Tract ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Hilar lymphadenopathy ,Magnetic resonance imaging ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Biliary tract ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Radiology ,medicine.symptom ,Liver function tests ,business ,Duct (anatomy) - Abstract
Purpose First, to evaluate and describe the clinical and MRI progression of patients with small duct primary sclerosing cholangitis (sdPSC), and second, to look for MRI features associated with disease progression to large duct PSC. Method 16 patients (7 female, 9 male; median age 27 years) with diagnosis of sdPSC and available MR imaging were included in this retrospective dual-center study. Liver function tests (LFTs) and imaging was reviewed in consensus by two radiologists at baseline and follow-up, and compared by means of non-parametric tests, with p Results At baseline and follow-up patients had a cholestatic liver profile with elevated LFTs. Progressive liver deformity, heterogeneous enhancement and hilar lymphadenopathy were common findings. In 9 patients follow-up MRI was available with a mean interval between imaging of 10.6 years (range 3.6−15.3 years). 5 patients (55.5 %) developed cholangiographic changes diagnostic of large duct PSC. No correlation was observed between MRI findings or LFTs at baseline and the endpoint of developing PSC typical cholangiographic changes at follow-up imaging (p > 0.05). Conclusions More than half of sdPSC patients developed cholangiographic changes, supporting that sdPSC may be an early stage of large duct PSC rather than an entity of its own. Larger studies are needed to address the value of MRI for prediction of sdPSC disease progression.
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- 2020
42. Diagnostic performance of a stepwise cytological algorithm for biliary malignancy in primary sclerosing cholangitis
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Stephan L. Haas, Katalin Dobra, Annika Bergquist, Erik von Seth, Urban Arnelo, Helena Ouchterlony, and Anders Hjerpe
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Adult ,Male ,Adolescent ,CA-19-9 Antigen ,Cytodiagnosis ,Cholangitis, Sclerosing ,Primary sclerosing cholangitis ,Biliary malignancy ,Cholangiocarcinoma ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Predictive Value of Tests ,Cytology ,medicine ,Biomarkers, Tumor ,Humans ,In patient ,Biliary Tract ,Early Detection of Cancer ,In Situ Hybridization, Fluorescence ,Aged ,Retrospective Studies ,Cholangiopancreatography, Endoscopic Retrograde ,Sweden ,Hepatology ,business.industry ,Brush cytology ,Middle Aged ,medicine.disease ,University hospital ,Data Accuracy ,Liver Transplantation ,Bile Duct Neoplasms ,Dysplasia ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,business ,Algorithm ,Stepwise approach ,Algorithms - Abstract
Background and aims Detection of early cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) is challenging. The aim of this study was to evaluate the diagnostic accuracy of a stepwise approach to biliary brush cytology with sequential use of fluorescence in-situ hybridization (FISH) for the detection of biliary malignancy in PSC. Method We retrospectively studied consecutive patients with PSC who underwent biliary brushings at Karolinska University Hospital between 2009 and 2015 (n = 208). Brush samples were categorized as benign, equivocal (atypical or suspicious) and malignant. Equivocal cases were further analysed with FISH. Samples with a malignant cytology or positive FISH were considered positive. The diagnosis was determined after 12 months of follow-up. Results The diagnosis CCA was confirmed in 15 patients (7%), high-grade dysplasia in three patients, and low-grade dysplasia in five patients at follow-up. Using the diagnostic algorithm, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for a diagnosis of CCA were 80% (95%CI 52%-96%), 96% (95%CI 92%-98%), 60% (95%CI 36%-81%) and 98% (95% CI 95%-100%). In patients with equivocal cytology (n = 61), the sensitivity for CCA diagnosis increased to 100% (95%CI 72%-100%) with a lower PPV of 58% (95%CI 34%-78%). The diagnostic accuracy for detection of CCA in all patients was 95% (95%CI 91%-97%). Conclusion Biliary brush cytology with sequential use of FISH in equivocal cases seems to be a highly predictive diagnostic test for CCA in PSC. These results support the use of FISH when cytology is equivocal for detection of biliary malignancy in PSC.
- Published
- 2018
43. Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells
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Urban Arnelo, Marcus Reuterwall-Hansson, Ammar Barakat, Erik von Seth, Christine L. Zimmer, Annika Bergquist, Martin A. Ivarsson, and Niklas K. Björkström
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0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Immunology ,Cell ,Cholangitis, Sclerosing ,Inflammation ,Mucosal associated invariant T cell ,Biology ,Chronic liver disease ,digestive system ,Inflammatory bowel disease ,Mucosal-Associated Invariant T Cells ,Primary sclerosing cholangitis ,Immunophenotyping ,Pathogenesis ,03 medical and health sciences ,Immune system ,medicine ,Escherichia coli ,Immunology and Allergy ,Humans ,Cells, Cultured ,Escherichia coli Infections ,Aged ,digestive, oral, and skin physiology ,Middle Aged ,medicine.disease ,digestive system diseases ,030104 developmental biology ,medicine.anatomical_structure ,Blood Circulation ,Cytokines ,Female ,Bile Ducts ,medicine.symptom - Abstract
Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC-patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.
- Published
- 2018
44. Restorative Surgery in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis Following a Colectomy
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Matteo Bottai, Ola Olén, Anders Ekbom, Pär Myrelid, Caroline Nordenvall, Per Nilsson, and Annika Bergquist
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Male ,endocrine system diseases ,medicine.medical_treatment ,Gastroenterology ,Cohort Studies ,0302 clinical medicine ,Risk Factors ,Immunology and Allergy ,Registries ,Child ,Colectomy ,Aged, 80 and over ,digestive, oral, and skin physiology ,Hazard ratio ,Proctocolectomy, Restorative ,Middle Aged ,Ulcerative colitis ,030220 oncology & carcinogenesis ,Child, Preschool ,030211 gastroenterology & hepatology ,Female ,Cohort study ,Adult ,medicine.medical_specialty ,Adolescent ,Cholangitis, Sclerosing ,digestive system ,Primary sclerosing cholangitis ,Stoma ,03 medical and health sciences ,Young Adult ,Age Distribution ,Internal medicine ,medicine ,Humans ,Sex Distribution ,Aged ,Sweden ,business.industry ,Proportional hazards model ,Infant, Newborn ,Infant ,Plastic Surgery Procedures ,medicine.disease ,Survival Analysis ,digestive system diseases ,Concomitant ,Multivariate Analysis ,Colitis, Ulcerative ,business - Abstract
Background Studies on surgical procedures in patients with concomitant primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have mainly been restricted to single centers. The aim was to compare surgical treatment of UC with or without PSC in a nationwide study. Methods A cohort study including all patients diagnosed with UC between 1987 and 2014 in Sweden was undertaken. The impact of PSC on the risk of colectomy, the chance of restorative surgery, and risk of failure (presence of a stoma) following restorative surgery were estimated. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models. Results Of 49 882 UC patients, 2079 had a PSC diagnosis at the end of follow-up. The risk of colectomy was unaffected by PSC diagnosis, whereas the chance of restorative surgery was elevated in PSC-UC patients (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.02-1.44). Ileorectal anastomosis (IRA) was performed in 63% of the PSC-UC patients and 43% of the non-PSC-UC-patients, and the corresponding numbers for ileal pouch anal anastomosis (IPAA) were 35% and 53%. There was no significantly increased risk of failure following restorative surgery in PSC patients (HR, 1.44; 95% CI, 0.93-2.22). In PSC-UC patients, the cumulative failure rates following an IRA at 3 and 5 years were 15% and 18%, and following an IPAA they were 11% and 18%, respectively. Conclusions Presence of PSC is not associated with the risk of colectomy, whereas the chance of restorative surgery in PSC-UC patients is higher than in UC alone.
- Published
- 2018
45. Editorial: the role of colonic inflammation in the progression of liver disease in primary sclerosing cholangitis-Authors' reply and Letter: the effects of colectomy prior to the diagnosis of primary sclerosing cholangitis on prognosis may have been overestimated
- Author
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Annika Bergquist and Caroline Nordenvall
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Cholangitis, Sclerosing ,Inflammation ,Gastroenterology ,Primary sclerosing cholangitis ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Colectomy ,Hepatology ,business.industry ,Liver Diseases ,medicine.disease ,Prognosis ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Published
- 2018
46. Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study
- Author
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Maria Castedal, Allan Rasmussen, Lina Lindström, Kirsten Muri Boberg, Helena Isoniemi, Matteo Bottai, Andreas A. Rostved, Kristin Kaasen Jørgensen, and Annika Bergquist
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Cholangitis, Sclerosing ,Liver transplantation ,Scandinavian and Nordic Countries ,Inflammatory bowel disease ,Gastroenterology ,Tacrolimus ,Primary sclerosing cholangitis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Primary biliary cirrhosis ,Recurrence ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,Registries ,Child ,Colectomy ,Aged ,Proportional Hazards Models ,Immunosuppression Therapy ,business.industry ,Graft Survival ,Immunosuppression ,Middle Aged ,medicine.disease ,Inflammatory Bowel Diseases ,Prognosis ,digestive system diseases ,3. Good health ,Liver Transplantation ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,business ,Cholangiography - Abstract
The risk for recurrent primary sclerosing cholangitis (rPSC) after liver transplantation is associated with inflammatory bowel disease (IBD). We assessed the frequency of rPSC and studied risk factors for recurrent disease with special focus on IBD. We also evaluated the importance of rPSC for prognosis.All liver transplanted PSC patients in the Nordic countries between 1984 and 2007 (n = 440), identified by the Nordic Liver Transplant Registry, were studied. Data were retrieved from patients' chart reviews. Multivariable Cox regression models were used to calculate risk factors for rPSC and death.Of the 440 patients with a follow-up time after liver transplantation of 3743 patient years, rPSC was diagnosed in 19% (n = 85). Colectomy before liver transplantation was associated with a reduced risk of rPSC (HR 0.49; 95% CI, 0.26-0.94, p = 0.033). Neither high IBD activity nor presence of IBD flares before or after liver transplantation was associated with rPSC. Treatment with tacrolimus was an independent risk factor associated with increased risk for rPSC (HR, 1.81; 95% CI, 1.15-2.86, p = 0.010). The risk of dying or needing a re-transplantation after rPSC was increased in all age groups, but highest in patients transplanted before 40 years of age (HR 7.3; 95% CI, 4.1-12.8, p = 0.0001).This study confirms that colectomy before liver transplantation is associated with a decreased risk of rPSC. Inflammatory activity of IBD was not associated with the risk of rPSC. Tacrolimus was an independent risk factor for PSC recurrence and its use as first line immunosuppression in PSC needs further study.
- Published
- 2018
47. GS-10-A germline mutation in SEMA4D leads to a familial syndrome of sclerosing cholangitis
- Author
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Jeff E. Mold, Jon K. Laerdahl, Martin Cornillet, Espen Melum, Geetha Venkatesh, Kjetil Taskén, Sigrid S. Skånland, Niklas K. Björkström, Tom H. Karlsen, Xiaojun Jiang, Andre Franke, Annika Bergquist, Britt-Sabina Petersen, and Kimia T. Maleki
- Subjects
Germline mutation ,Hepatology ,Cancer research ,SEMA4D ,Biology - Published
- 2019
48. Liver transplantation in the Nordic countries – An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013
- Author
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Helena Isoniemi, Styrbjörn Friman, Erik Schrumpf, Marie Larsson, Bjarte Fosby, Bo-Göran Ericzon, Christina Wibeck, Heikki Mäkisalo, Arno Nordin, Tom H. Karlsen, Kristian Bjøro, Susanne Keiding, Pål-Dag Line, Aksel Foss, Allan Rasmussen, Michael Olausson, Stein Foss, Leena Toivonen, Annika Bergquist, Espen Melum, Ina Marie Andersen, Truls Sanengen, Krister Höckerstedt, Greg Nowak, Kirsten Muri Boberg, Gunnar Söderdahl, Mette Gotlieb, Maria Castedal, Henrik Gjertsen, and William Bennet
- Subjects
Adult ,Male ,Reoperation ,Alcoholic liver disease ,medicine.medical_specialty ,organ allocation ,Tissue and Organ Procurement ,Waiting Lists ,end-stage liver disease ,medicine.medical_treatment ,indication ,Milan criteria ,Liver transplantation ,registry ,Scandinavian and Nordic Countries ,Primary sclerosing cholangitis ,Liver disease ,Primary biliary cirrhosis ,Biliary atresia ,Internal medicine ,Medicine ,Humans ,Registries ,Survival rate ,Aged ,Retrospective Studies ,liver transplantation ,business.industry ,Gastroenterology ,Middle Aged ,medicine.disease ,Liver Transplantation ,3. Good health ,Surgery ,Intention to Treat Analysis ,Survival Rate ,outcome ,Kidney Failure, Chronic ,Original Article ,Female ,business - Abstract
AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013.MATERIALS AND METHODS: The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report.RESULTS: Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively.CONCLUSION: The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).
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- 2015
49. Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
- Author
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Fredrik Rorsman, Hanns-Ulrich Marschall, Mårten Werner, Emma Nilsson, Ola Weiland, Annika Bergquist, Åsa Danielsson Borssén, Stergios Kechagias, Hans Verbaan, and Nils Nyhlin
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pediatrics ,Cirrhosis ,Adolescent ,Autoimmune hepatitis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Age Distribution ,Risk Factors ,Cause of Death ,Epidemiology ,Prevalence ,Medicine ,Humans ,Registries ,Sex Distribution ,Child ,Aged ,Retrospective Studies ,Aged, 80 and over ,Sweden ,business.industry ,Incidence (epidemiology) ,Incidence ,Gastroenterology ,Infant, Newborn ,Infant ,Middle Aged ,medicine.disease ,Survival Analysis ,Liver Transplantation ,Hepatitis, Autoimmune ,030220 oncology & carcinogenesis ,Child, Preschool ,Immunology ,Cohort ,030211 gastroenterology & hepatology ,Female ,business - Abstract
Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce. Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Västerbotten in Northern Sweden.AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p .001) and died younger than women (p = .002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p .001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.
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- 2017
50. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis A cohort study
- Author
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Hanns-Ulrich Marschall, Annika Bergquist, Hans Verbaan, Ola Weiland, Nils Nyhlin, Åsa Danielsson Borssén, Stergios Kechagias, Emma Nilsson, Richard Palmqvist, Mårten Werner, and Fredrik Rorsman
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Liver Cirrhosis ,Male ,Pathology ,Cirrhosis ,Biopsy ,General Practice ,Autoimmune hepatitis ,Severity of Illness Index ,Gastroenterology ,Hospitals, University ,0302 clinical medicine ,immune system diseases ,Fibrosis ,Medicine ,Young adult ,Child ,medicine.diagnostic_test ,autoimmune liver disease ,autoimmune hepatitis ,cirrhosis ,fibrosis ,inflammation ,General Medicine ,Middle Aged ,Hepatitis, Autoimmune ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,Adolescent ,Observational Study ,Gastroenterology and Hepatology ,Young Adult ,03 medical and health sciences ,Internal medicine ,Severity of illness ,Gastroenterologi ,Humans ,Aged ,Inflammation ,Sweden ,Hepatitis ,business.industry ,medicine.disease ,digestive system diseases ,Allmänmedicin ,business - Abstract
Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis. A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared. Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy. Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients. Funding Agencies|Albireo, Gothenburg, Sweden; Intercept, San Diego, CA, USA; Bengt Ihres fund; Vasterbotten County, Umea University Hospital
- Published
- 2017
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