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2. Follow-up magnetic resonance imaging/3D-magnetic resonance cholangiopancreatography in patients with primary sclerosing cholangitis: challenging for experts to interpret

Author

Zenouzi, R., Liwinski, T., Yamamura, J., Weiler-Normann, C., Sebode, M., Keller, S., Lohse, A. W., Schramm, C., Aabakken, L., Arrivé, L., Bowlus, C. L., Bungay, H., van Buuren, H. R., Cardinale, V., Carey, E. J., Chazouillères, O., Cheung, A., Culver, E. L., Dufour, J. F., Dumonceau, J. M., Eaton, J. E., Eddowes, P. J., Färkkilä, M., Floreani, A., Franceschet, I., Hohenester, S. D., Kemmerich, G., Krawczyk, M., Zimmer, V., Lenzen, H., Levy, C., Marschall, H. U., Marzioni, M., Motta, R., Muratori, L., Pereira, S. P., Poley, J. W., Rimola, J., Ringe, K. I., Rushbrook, S., Simpson, B. W., Schrumpf, E., Spina, J. C., Terziroli Beretta-Piccoli, B., Trauner, M., Tringali, A., Venkatesh, S. K., Vesterhus, M., Villamil, A., Weismüller, T. J., Ytting, H., Zenouzi, R., Liwinski, T., Yamamura, J., Weiler-Normann, C., Sebode, M., Keller, S., Lohse, A.W., Schramm, C., Aabakken, L., Arrivé, L., Bowlus, C.L., Bungay, H., van Buuren, H.R., Cardinale, V., Carey, E.J., Chazouillères, O., Cheung, A., Culver, E.L., Dufour, J.F., Dumonceau, J.M., Eaton, J.E., Eddowes, P.J., Färkkilä, M., Floreani, A., Franceschet, I., Hohenester, S.D., Kemmerich, G., Krawczyk, M., Zimmer, V., Lenzen, H., Levy, C., Marschall, H.U., Marzioni, M., Motta, R., Muratori, L., Pereira, S.P., Poley, J.W., Rimola, J., Ringe, K.I., Rushbrook, S., Simpson, B.W., Schrumpf, E., Spina, J.C., Terziroli Beretta-Piccoli, B., Trauner, M., Tringali, A., Venkatesh, S.K., Vesterhus, M., Villamil, A., Weismüller, T.J., Ytting, H., Culver, E, and Gastroenterology & Hepatology

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Cholangiopancreatography, Magnetic Resonance, Cholangitis, Sclerosing, Constriction, Pathologic, Primary sclerosing cholangitis, Cholangiocarcinoma, Diagnosis, Differential, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Surveys and Questionnaires, Image Interpretation, Computer-Assisted, medicine, Humans, Pharmacology (medical), In patient, Expert Testimony, Cholangiopancreatography, Endoscopic Retrograde, Magnetic resonance cholangiopancreatography, Endoscopic retrograde cholangiopancreatography, Hepatology, medicine.diagnostic_test, business.industry, Elevated total bilirubin, Gastroenterology, Reproducibility of Results, Magnetic resonance imaging, Middle Aged, medicine.disease, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Clinical Competence, Radiology, Bilirubin levels, business, Follow-Up Studies
Abstract

Background: In patients with primary sclerosing cholangitis follow‐up magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is performed by many centres, particularly for the early detection of biliary malignancies and strictures. Clinically meaningful MRI‐based definitions of primary sclerosing cholangitis related complications are, however, lacking.Aim: To investigate how primary sclerosing cholangitis experts interpret follow‐up MRI/MRCP with a focus on conclusions that may impact clinical decision‐making in primary sclerosing cholangitis.Methods: Within the International Primary Sclerosing Cholangitis Study Group, an online survey on 16 real‐life primary sclerosing cholangitis cases including clinical and biochemical information as well as a T2‐weighted liver MRI/3D‐MRCP was conducted. The interpretation of images and subsequent recommendations were assessed using a multiple‐choice questionnaire. An inter‐rater reliability calculation (Fleiss′ kappa) was performed and factors potentially affecting the interpretation of magnetic resonance images were analysed using generalised linear mixed‐effect models.Results: Forty‐four members/associates of the International Primary Sclerosing Cholangitis Study Group (median experience in the care of primary sclerosing cholangitis patients: 14 years) completed the survey. The MRI interpretation significantly varied among the participants. The lowest agreement was found with respect to the indication to perform subsequent endoscopic retrograde cholangiopancreatography (ERCP; Κ = 0.12, 95%CI 0.11‐0.14). Elevated total bilirubin was the variable with the strongest effect on the rate of suspected dominant strictures, cholangiocarcinoma or ERCP recommendations. Liver cirrhosis did not prevent participants from recommending ERCP. Overall, the survey participants′ recommendations contrasted the real‐life management and outcome.Conclusions: In primary sclerosing cholangitis, the interpretation of follow‐up MRI/3D‐MRCP significantly varies even among experts and seems to be primarily affected by bilirubin levels. Generally accepted MRI‐based definitions of primary sclerosing cholangitis‐related complications are urgently needed.

Published
2018

6. Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis. (Liver Disease)

Author

Bjornsson, E., Boberg, K.M., Cullen, S., Fleming, K., Clausen, O.P., Fausa, O., Schrumpf, E., and Chapman, R.W.

Subjects
Mortality -- Norway -- Sweden -- United Kingdom, Cholangitis -- Patient outcomes, Health, Patient outcomes
Abstract

Background: Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but a normal cholangiogram are considered to have small duct PSC. The natural history of [...]

Published
2002

13. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

Author

Weismueller, T, Strassburg, C, Trivedi, P, Hirschfield, G, Bergquist, A, Said, K, Imam, M, Lazaridis, K, Juran, B, Cheung, A, Lindor, K, Lenzen, H, Manns, M, Ponsioen, C, Beuers, U, Holm, K, Naess, S, Karlsen, T, Schrumpf, E, Boberg, K, Gotthardt, D, Rupp, C, Faerkkilae, M, Jokelainen, K, Marschall, H, Benito De Valle, M, Thorburn, D, Saffioti, F, Weersma, R, Fevery, J, Mueller, T, Chazouillãres, O, Schulze, K, Schramm, C, Almer, S, Pereira, S, Levy, C, Mason, A, Bowlus, C, Floreani, A, Halilbasic, E, Trauner, M, Yimam, K, Milkiewicz, P, Huynh, D, Pares, A, Manser, C, Dalekos, G, Eksteen, B, INVERNIZZI, PIETRO, Berg, C, Kirchner, G, Sarrazin, C, Zimmer, V, Fabris, L, Braun, F, Marzioni, M, Chapman, R, Hansen, B, Hansen, B., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Weismueller, T, Strassburg, C, Trivedi, P, Hirschfield, G, Bergquist, A, Said, K, Imam, M, Lazaridis, K, Juran, B, Cheung, A, Lindor, K, Lenzen, H, Manns, M, Ponsioen, C, Beuers, U, Holm, K, Naess, S, Karlsen, T, Schrumpf, E, Boberg, K, Gotthardt, D, Rupp, C, Faerkkilae, M, Jokelainen, K, Marschall, H, Benito De Valle, M, Thorburn, D, Saffioti, F, Weersma, R, Fevery, J, Mueller, T, Chazouillãres, O, Schulze, K, Schramm, C, Almer, S, Pereira, S, Levy, C, Mason, A, Bowlus, C, Floreani, A, Halilbasic, E, Trauner, M, Yimam, K, Milkiewicz, P, Huynh, D, Pares, A, Manser, C, Dalekos, G, Eksteen, B, Invernizzi, P, Berg, C, Kirchner, G, Sarrazin, C, Zimmer, V, Fabris, L, Braun, F, Marzioni, M, Chapman, R, Hansen, B, Clinicum, Department of Medicine, Gastroenterologian yksikkö, HUS Abdominal Center, Universitat de Barcelona, Gastroenterology & Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Male, Risk Stratification, Time Factors, Cholangitis, POPULATION-BASED COHORT, Ulcerative, Kaplan-Meier Estimate, Gastroenterology, Inflammatory bowel disease, Sclerosing, 0302 clinical medicine, Crohn Disease, Retrospective Studie, MED/12 - GASTROENTEROLOGIA, Risk Factors, Autoimmune Liver Disease, Multivariate Analysi, Crohn's disease, Cholestasis, Incidence, Hazard ratio, Immune-Mediated Liver Disease, Adult, Age Distribution, Australia, Chi-Square Distribution, Cholangitis, Sclerosing, Colitis, Ulcerative, Disease Progression, Europe, Female, Humans, Liver Transplantation, Middle Aged, Multivariate Analysis, North America, Phenotype, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sex Distribution, Young Adult, Colitis, Ulcerative colitis, Inflamació, CROHNS-DISEASE, 3. Good health, ULCERATIVE-COLITIS, Cholestasi, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Human, medicine.medical_specialty, Time Factor, Prognosi, Lower risk, Article, Primary sclerosing cholangitis, 03 medical and health sciences, Colitis ulcerosa, Internal medicine, medicine, GENOME-WIDE ASSOCIATION, PRIMARY BILIARY-CIRRHOSIS, Inflammation, Hepatology, business.industry, Proportional hazards model, Risk Factor, CLINICAL PRESENTATION, Retrospective cohort study, DOSE URSODEOXYCHOLIC ACID, NATURAL-HISTORY, medicine.disease, digestive system diseases, 3121 General medicine, internal medicine and other clinical medicine, RISK-FACTORS, Proportional Hazards Model, business, SINGLE-CENTER
Abstract

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P

Published
2017

18. International Autoimmune Hepatitis Group* Report: review of criteria for diagnosis of autoimmune hepatitis

Author

Alvarez, F., Berg, P. A., Bianchi, F. B., Bianchi, L., Burroughs, A. K., Cancado, E. L., Chapman, R. W., Cooksley, W. G. E., Czaja, A. J., Desmet, V. J., Donaldson, P. T., Eddleston, A. L. W. F., Fainboim, L., Heathcote, J., Homberg, J.-C., Hoofnagle, J. H., Kakumu, S., Krawitt, E. L., Mackay, I. R., MacSween, R. N. M., Maddrey, W. C., Manns, M. P., McFarlane, I. G., Meyer zum Büschenfelde, K.-H., Mieli-Vergani, G., Nakanuma, Y., Nishioka, M., Penner, E., Porta, G., Portmann, B. C., Reed, W. D., Rodes, J., Schalm, S. W., Scheuer, P. J., Schrumpf, E., Seki, T., Toda, G., Tsuji, T., Tygstrup, N., Vergani, D., and Zeniya, M.

Published
1999

20. Pustuløst legemiddelutslett

Author

Rizvi Smh and Schrumpf E

Subjects
medicine.medical_specialty, business.industry, medicine, General Medicine, medicine.disease, business, Dermatology, Drug eruption
Published
2018

23. Lipid antigens in bile from patients with chronic liver diseases activate natural killer T cells.

Author

Valestrand, L., Berntsen, N. L., Zheng, F., Schrumpf, E., Hansen, S. H., Karlsen, T. H., Blumberg, R. S., Hov, J. R., Jiang, X., and Melum, E.

Subjects
CYTOTOXIC T cells, KILLER cells, CHRONICALLY ill, BILE, ANTIGENS
Abstract

Summary: Natural killer T (NKT) cells are an abundant subset of liver lymphocytes activated by lipid antigens presented on CD1d molecules that are expressed by cholangiocytes. We aimed to determine if bile from patients with chronic liver diseases contains antigenic lipids that can activate NKT cells. Using murine invariant (24.7, 24.8 and DN32.D3) and non‐invariant (14S.6, 14S.7 and 14S.10) NKT hybridomas we investigated the presence of lipid antigens in bile collected from the gallbladder of patients undergoing liver transplantation due to end‐stage liver disease. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing. We found that the patient bile samples contain antigens that activate both invariant and non‐invariant NKT hybridomas (24.7, 24.8, DN32.D3, 14S.6, 14S.7 and 14S.10), as demonstrated by activation of at least one hybridoma by eight of 10 bile samples. Activation at high dilutions suggests that some antigens are highly potent. We used the non‐invariant NKT hybridoma 14S.6 to screen 21 additional patient bile samples for NKT‐reactivity and demonstrated that 12 of 21 bile samples resulted in activation, three of which gave a strong activation. Four of 12 activating bile samples contained microbial DNA. Our results reveal an immunological pathway that could be of critical importance in biliary immunology. [ABSTRACT FROM AUTHOR]

Published
2021
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24. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Author

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, 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, and Weersma, R

Abstract

Objective Primary 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. Design We 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. Results We 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. Conclusion We 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.

Published
2018

27. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

Author

Weismüller, T.J. (Tobias J.), Strassburg, C.P. (Christian P.), Trivedi, A. (Amber), Hirschfield, G.M. (Gideon), Trivedi, P.J. (Palak J.), Bergquist, A. (Annika), Said, K. (Karouk), Imam, M. (Mohamad), Lazaridis, K.N. (Konstantinos N.), Juran, B.D. (Brian D.), Cheung, A.C. (Angela C.), Lindor, K.D. (Keith), Lenzen, H. (Henrike), Manns, M.P. (Michael), Ponsioen, C.Y. (Cyril), Beuers, U. (Ulrich), Holm, K. (Kristian), Naess, S. (Sigrid), Karlsen, T.H. (Tom), Schrumpf, E. (Erik), Boberg, K.M. (Kirsten M.), Gotthardt, D. (Daniel), Rupp, C. (Christian), Färkkilä, M. (Martti), Jokelainen, K. (Kalle), Marschall, H.-U., Benito de Valle, M. (Maria), Thorburn, D. (Douglas), Saffioti, F. (Francesca), Weersma, R.K. (Rinse K.), Fevery, J. (J.), Mueller, T. (Tobias), Chazouillères, O. (Olivier), Schulze, K. (Kornelius), Schramm, C. (Christoph), Almer, S. (Sven), Pereira, S.P. (Stephen P.), Levy, C. (Cynthia), Mason, A. (Andrew), Bowlus, C.L. (Christopher L.), Floreani, A. (Annarosa), Halilbasic, E. (Emina), Trauner, M. (Michael), Yimam, K.K. (Kidist K.), Milkiewicz, P. (Piotr), Huynh, D.K. (Dep K.), Parés, A. (Albert), Manser, C.N. (Christine N.), Dalekos, G. (George), Eksteen, B. (Bertus), Invernizzi, P. (Pietro), Berg, C.P. (Christoph P.), Kirchner, G.I. (Gabi I.), Sarrazin, C. (Christoph), Zimmer, V. (Vincent), Fabris, L. (Luca), Braun, F. (Felix), Marzioni, M. (Marco), Chapman, R.W. (Roger), Chapman, R.W. (Roger W.), Lindor, K.D. (Keith D.), Karlsen, T.H. (Tom H.), Hansen, B.E. (Bettina E.), Hansen, B.E. (Bettina), Weismüller, T.J. (Tobias J.), Strassburg, C.P. (Christian P.), Trivedi, A. (Amber), Hirschfield, G.M. (Gideon), Trivedi, P.J. (Palak J.), Bergquist, A. (Annika), Said, K. (Karouk), Imam, M. (Mohamad), Lazaridis, K.N. (Konstantinos N.), Juran, B.D. (Brian D.), Cheung, A.C. (Angela C.), Lindor, K.D. (Keith), Lenzen, H. (Henrike), Manns, M.P. (Michael), Ponsioen, C.Y. (Cyril), Beuers, U. (Ulrich), Holm, K. (Kristian), Naess, S. (Sigrid), Karlsen, T.H. (Tom), Schrumpf, E. (Erik), Boberg, K.M. (Kirsten M.), Gotthardt, D. (Daniel), Rupp, C. (Christian), Färkkilä, M. (Martti), Jokelainen, K. (Kalle), Marschall, H.-U., Benito de Valle, M. (Maria), Thorburn, D. (Douglas), Saffioti, F. (Francesca), Weersma, R.K. (Rinse K.), Fevery, J. (J.), Mueller, T. (Tobias), Chazouillères, O. (Olivier), Schulze, K. (Kornelius), Schramm, C. (Christoph), Almer, S. (Sven), Pereira, S.P. (Stephen P.), Levy, C. (Cynthia), Mason, A. (Andrew), Bowlus, C.L. (Christopher L.), Floreani, A. (Annarosa), Halilbasic, E. (Emina), Trauner, M. (Michael), Yimam, K.K. (Kidist K.), Milkiewicz, P. (Piotr), Huynh, D.K. (Dep K.), Parés, A. (Albert), Manser, C.N. (Christine N.), Dalekos, G. (George), Eksteen, B. (Bertus), Invernizzi, P. (Pietro), Berg, C.P. (Christoph P.), Kirchner, G.I. (Gabi I.), Sarrazin, C. (Christoph), Zimmer, V. (Vincent), Fabris, L. (Luca), Braun, F. (Felix), Marzioni, M. (Marco), Chapman, R.W. (Roger), Chapman, R.W. (Roger W.), Lindor, K.D. (Keith D.), Karlsen, T.H. (Tom H.), Hansen, B.E. (Bettina E.), and Hansen, B.E. (Bettina)

Abstract

Background & Aims Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. Methods We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR

Published
2017
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31. Association of the tumour necrosis factor α -- 308 but not the interleukin 10 -- 627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis

Author

Mitchell, S A., Grove, J, Spurkland, A, Boberg, K M., Fleming, K A., Day, C P., Schrumpf, E, and Chapman, R W.

Subjects
Comorbidity -- Analysis -- Research, Interleukin-10 -- Physiological aspects -- Research -- Analysis, Cholangitis -- Causes of -- Research, Tumor necrosis factor -- Physiological aspects -- Research -- Analysis, Disease susceptibility -- Research, Health, Analysis, Physiological aspects, Research, Causes of
Abstract

Abstract Background and aims--Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology. Abnormalities in immune regulation and genetic associations suggest that PSC is an immune mediated [...]

Published
2001

32. Proteomic Analysis of Liver Fibrotic Septa and Periportal Spaces in Primary Sclerosing Cholangitis, Primary Biliary Cholangitis and Alcoholic Liver Disease

Author

Mazza, G., primary, Telese, A., additional, Schrumpf, E., additional, Gilbertson, J., additional, Rendell, N., additional, Lombardi, B., additional, Godovac-Zimmermann, J., additional, Taylor, G.W., additional, Thorburn, D., additional, Karlsen, T.H., additional, and Pinzani, M., additional

Published
2016
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34. Norursodeoxycholic Acid Improves Cholestasis in Primary Sclerosing Cholangitis: Results of a Phase II Dose Finding Study

Author

Trauner, M., primary, Fickert, P., additional, Hirschfield, G., additional, Reiter, F., additional, Altorjay, I., additional, Marschall, H.U., additional, Färkkilä, M., additional, Schramm, C., additional, Spengler, U., additional, Chapman, R., additional, Bergquist, A., additional, Schrumpf, E., additional, Nevens, F., additional, Halilbasic, E., additional, Greinwald, R., additional, Proels, M., additional, and Manns, M.P., additional

Published
2016
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35. Genotype-Phenotype Analysis across 130,422 Genetic Variants Identifies Rspo3 as the First Genome-Wide Significant Modifier Gene in Primary Sclerosing Cholangitis

Author

Alberts, R., primary, de Vries, E.M., additional, Alexander, G., additional, Alvaro, D., additional, Bergquist, A., additional, Beuers, U., additional, Björnsson, E., additional, Boberg, K.M., additional, Bowlus, C.L., additional, Chapman, R.W., additional, Chazouilléres, O., additional, Cheung, A., additional, Dalekos, G., additional, Eksteen, B., additional, Eaton, J.E., additional, Ellinghaus, D., additional, Färkkilä, M., additional, Festen, E.A., additional, Floreani, A., additional, Folseraas, T., additional, Goode, E., additional, Gotthardt, D.N., additional, Hirschfield, G.M., additional, van Hoek, B., additional, Hohenester, S., additional, Holm, K., additional, Hov, J.R., additional, Imhann, F., additional, Invernizzi, P., additional, Jiang, X., additional, Juran, B.D., additional, Lazaridis, K.N., additional, Leppa, V., additional, Liu, J.Z., additional, Löfberg, J., additional, Manns, M.P., additional, Marschall, H.-U., additional, Marzioni, M., additional, Mason, A.L., additional, Melum, E., additional, Müller, T., additional, Milkiewicz, P., additional, Pares, A., additional, Pelkonen, V., additional, Pinzani, M., additional, Rombouts, K., additional, Rupp, C., additional, Rushbrook, S.M., additional, Rust, C., additional, Sampaziotis, F., additional, Sandford, R.N., additional, Schramm, C., additional, Schreiber, S., additional, Schrumpf, E., additional, Silverberg, M., additional, Srivastava, B., additional, Sterneck, M., additional, Teufel, A., additional, Tittmann, L., additional, Vallier, L., additional, Vila, A.V., additional, de Vries, B.A., additional, Weismüller, T.J., additional, Wijmenga, C., additional, Zachou, K., additional, Franke, A., additional, Anderson, C.A., additional, Karlsen, T.H., additional, Ponsioen, C.Y., additional, and Weersma, K., additional

Published
2016
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40. O082 : The gut microbiota in primary sclerosing cholangitis differs from that of healthy controls and ulcerative colitis patients without biliary disease

Author

Kummen, M., primary, Holm, K., additional, Anmarkrud, J.A., additional, Vesterhus, M., additional, Høivik, M.L., additional, Trøseid, M., additional, Marschall, H.-U., additional, Schrumpf, E., additional, Moum, B., additional, Aukrust, P., additional, Karlsen, T.H., additional, and Hov, J.R., additional

Published
2015
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46. Chemopreventive effect of ursodeoxycholic acid in primary sclerosing cholangitis?

Author

Brandsæter, B., primary, Isoniemi, H., additional, Broomé, U., additional, Olausson, M., additional, Bäckman, L., additional, Hansen, B., additional, Oksanen, A., additional, Ericzon, B. -G., additional, Höckerstedt, K., additional, Mäkisalo, H., additional, Kirkegaard, P., additional, Friman, S., additional, Bjøro, K., additional, and Schrumpf, E., additional

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48. O133 NOVEL PROTEIN MARKERS IDENTIFIED IN BILE AND SERUM ARE ASSOCIATED WITH A DIAGNOSIS OF PRIMARY SCLEROSING CHOLANGITIS, DISEASE SEVERITY, AND TRANSPLANT-FREE SURVIVAL

Author

Vesterhus, M., primary, Holm, A., additional, Hov, J.R., additional, Andersen, I.M., additional, Schrumpf, E., additional, Paulsen, V., additional, Bjørnstad, M., additional, Lundin, K., additional, Zweers, S.J.L.B., additional, Vatn, M., additional, Schaap, F.G., additional, Ueland, T., additional, Røsjø, H., additional, Moum, B., additional, Ponsioen, C.Y., additional, Boberg, K.M., additional, Färkkilä, M., additional, Lund-Johansen, F., additional, and Karlsen, T.H., additional

Published
2014
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49. P363 ENHANCED LIVER FIBROSIS SCORE PREDICTS TRANSPLANT-FREE SURVIVAL IN PSC INDEPENDENTLY OF THE MAYO RISK SCORE

Author

Vesterhus, M., primary, Hov, J.R., additional, Holm, A., additional, Schrumpf, E., additional, Godang, K., additional, Andersen, I.M., additional, Næss, S., additional, Røsjø, H., additional, Vatn, M., additional, Gilja, O.H., additional, Lund-Johansen, F., additional, Ponsioen, C.Y., additional, Färkkila, M., additional, Moum, B., additional, Ueland, T., additional, Boberg, K.M., additional, and Karlsen, T.H., additional

Published
2014
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50. O5 PRIMARY SCLEROSING CHOLANGITIS FROM A GLOBAL PERSPECTIVE – A MULTICENTER, RETROSPECTIVE, OBSERVATIONAL STUDY OF THE INTERNATIONAL PSC STUDY GROUP

Author

Weismüller, T.J., primary, Talwalkar, J.A., additional, Ponsioen, C.Y., additional, Gotthardt, D.N., additional, Marschall, H.-U., additional, Naess, S., additional, Holm, K., additional, Weersma, R.K., additional, Lazaridis, K.N., additional, Fevery, J., additional, Trivedi, P.J., additional, Schramm, C., additional, Chazouilleres, O., additional, Müller, T., additional, Farkkila, M., additional, Almer, S., additional, Pereira, S., additional, Mason, A.L., additional, Floreani, A., additional, Milkiewicz, P., additional, Harley, H., additional, Pares, A., additional, de Vries, L., additional, Manser, C., additional, Gatselis, N., additional, Berg, C., additional, Lenzen, H., additional, de Valle, M. Benito, additional, Imam, M., additional, Kirchner, G., additional, de Leuw, P., additional, Zimmer, V., additional, Fabris, L., additional, Braun, F., additional, Hirschfield, G.M., additional, Marzioni, M., additional, Juran, B.D., additional, Strassburg, C.P., additional, Beuers, U., additional, Manns, M.P., additional, Schrumpf, E., additional, Karlsen, T.H., additional, Bergquist, A., additional, and Boberg, K.M., additional

Published
2014
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