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  • 1.
    Adams, A.
    et al.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kalla, R.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, S.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Bonfiglio, F.
    BioCruces Health Research Institue, Bilbao, Spain.
    Nimmo, E.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kennedy, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Ventham, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, M.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Ricanek, P.
    Department of Gastroenterology, Akershus University, Akershus, Norway.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Söderholm, J.
    Department of Surgery, Linköping University Hospital, Linköping, Sweden;.
    Pierik, M.
    Department of Gastroenterology and Hepatology, Maastricht University Medical Center (MUMC), Maastricht, Netherlands.
    Törkvist, L.
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Gomollon, F.
    University Hospital Clinic Lozano Blesa, Zaragoza, Spain.
    Gut, I.
    CNAG-CRG Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
    Jahnsen, J.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Satsangi, J.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S108-S108Article in journal (Refereed)
  • 2.
    Agrawal, M.
    et al.
    The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA.
    Shrestha, Sarita
    Örebro University, School of Medical Sciences.
    Corn, G.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Nielsen, N. M.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Frisch, M.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Colombel, J. F.
    The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA.
    Jess, T.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    The epidemiology of inflammatory bowel diseases among immigrants to Denmark: A population-based cohort study2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no Suppl. 1, p. S006-S007Article in journal (Other academic)
  • 3.
    Agrawal, Manasi
    et al.
    The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Corn, Giulia
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Shrestha, Sarita
    Örebro University, School of Medical Sciences.
    Nielsen, Nete Munk
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Frisch, Morten
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Colombel, Jean-Frederic
    The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Jess, Tine
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Inflammatory bowel diseases among first-generation and second-generation immigrants in Denmark: a population-based cohort study2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 6, p. 1037-1043Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Our objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes.

    DESIGN: Using national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark.

    RESULTS: Among 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants.

    CONCLUSION: Relative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.

  • 4.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden; Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Andersson, K.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Leijonmarck, C. E.
    Department of Surgery, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Hedenborg, L.
    Department of Pathology, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    St Göran's Hospital, Stockholm, Sweden.
    Short-term starvation alters the free amino acid content of human intestinal mucosa1994In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 86, no 6, p. 653-662Article in journal (Refereed)
    Abstract [en]

    1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n=6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon.

    2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased.

    3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon.

    4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine. S. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.

  • 5.
    Alaedini, Armin
    et al.
    Institute of Human Nutrition, Columbia University Medical Center, New York NY, USA; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA .
    Lebwohl, Benjamin
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Wormser, Gary P.
    Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla NY, United States.
    Green, Peter H.
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York NY, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom.
    Borrelia infection and risk of celiac disease2017In: BMC Medicine, E-ISSN 1741-7015, Vol. 15, article id 169Article in journal (Refereed)
    Abstract [en]

    Background: Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

    Methods: Biopsy reports from all of Sweden's pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.

    Results: Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06-2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40-2.35), with the risk of disease being highest in the first year of follow-up.

    Conclusions: Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

  • 6.
    Al-Bluwi, Ghada S. M.
    et al.
    Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    AlNababteh, Asma H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Östlundh, Linda
    National Medical Library, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Al-Shamsi, Saif
    Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Prevalence of Celiac Disease in Patients With Turner Syndrome: Systematic Review and Meta-Analysis2021In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 674896Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Celiac disease (CD) is a multifactorial autoimmune disorder, and studies have reported that patients with Turner syndrome (TS) are at risk for CD. This systematic review and meta-analysis aimed to quantify the weighted prevalence of CD among patients with TS and determine the weighted strength of association between TS and CD.

    Methods: Studies published between January 1991 and December 2019 were retrieved from four electronic databases: PubMed, Scopus, Web of Science, and Embase. Eligible studies were identified and relevant data were extracted by two independent reviewers following specific eligibility criteria and a data extraction plan. Using the random-effects model, the pooled, overall and subgroup CD prevalence rates were determined, and sources of heterogeneity were investigated using meta-regression.

    Results: Among a total of 1,116 screened citations, 36 eligible studies were included in the quantitative synthesis. Nearly two-thirds of the studies (61.1%) were from European countries. Of the 6,291 patients with TS who were tested for CD, 241 were diagnosed with CD, with a crude CD prevalence of 3.8%. The highest and lowest CD prevalence rates of 20.0 and 0.0% were reported in Sweden and Germany, respectively. The estimated overall weighted CD prevalence was 4.5% (95% confidence interval [CI], 3.3-5.9, I-2, 67.4%). The weighted serology-based CD prevalence in patients with TS (3.4%, 95% CI, 1.0-6.6) was similar to the weighted biopsy-based CD prevalence (4.8%; 95% CI, 3.4-6.5). The strength of association between TS and CD was estimated in only four studies (odds ratio 18.1, 95% CI, 1.82-180; odds ratio 4.34, 95% CI, 1.48-12.75; rate ratio 14, 95% CI, 1.48-12.75; rate ratio 42.5, 95% CI, 12.4-144.8). Given the lack of uniformity in the type of reported measures of association and study design, producing a weighted effect measure to evaluate the strength of association between TS and CD was unfeasible.

    Conclusion: Nearly 1 in every 22 patients with TS had CD. Regular screening for CD in patients with TS might facilitate early diagnosis and therapeutic management to prevent adverse effects of CD such as being underweight and osteoporosis.

  • 7.
    Albshesh, Ahmad
    et al.
    Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Taylor, Joshua
    Department of Gastroenterology, Montreal General Hospital, Montreal QC, Canada.
    Savarino, Edoardo, V
    Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
    Truyens, Marie
    IBD Unit, Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
    Armuzzi, Alessandro
    IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
    Ribaldone, Davide G.
    Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy.
    Shitrit, Ariella Bar-Gil
    Shaare Zedek Medical Center, Faculty of Medicine, Digestive Diseases Institute, Hebrew University of Jerusalem, Jerusalem, Israel.
    Fibelman, Morine
    Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Molander, Pauliina
    Abdominal Center, Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.
    Liefferinckx, Claire
    Department of Gastroenterology, Erasme University Hopital, Brussels, Belgium.
    Nancey, Stephane
    Department of Gastroenterology, Hospices Civils de Lyon, University Claude Bernard Lyon, Lyon, France; INSERM, U1111, CIRI, Lyon, France.
    Korani, Mohamed
    Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester, UK; Manchester Academic Health Sciences, University of Manchester, Manchester, UK.
    Rutka, Mariann
    First Department of Medicine, University of Szeged, Szeged, Hungary.
    Barreiro-de Acosta, Manuel
    IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago, Spain.
    Domislovic, Viktor
    Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, Zagreb, Croatia.
    Suris, Gerard
    Digestive System Service, Bellvitge University Hospital, Catalan Institute of Health, Barcelona, Spain.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Alves, Catarina
    Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.
    Mpitouli, Afroditi
    Department of Gastroenterology, Venizeleion General Hospital, Heraklion, Crete, Greece.
    di Jiang, Caroline
    Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK.
    Tepes, Katja
    University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
    Coletta, Marina
    Department of Hepatology and Clinical Gastroenterology, ASST Santi Paolo e Carlo-Ospedale San Polo Universitario Milano Mariabeatrice, Milan, Italy.
    Foteinogiannopoulou, Kalliopi
    Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
    Gisbert, Javier P.
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain.
    Amir-Barak, Hadar
    IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Attauabi, Mohamed
    Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
    Seidelin, Jakob
    Department of Gastroenterology, Herlev University Hospital, Copenhagen, Denmark.
    Afif, Waqqas
    Department of Gastroenterology, Montreal General Hospital, Montreal QC, Canada.
    Marinelli, Carla
    Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
    Lobaton, Triana
    IBD Unit, Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
    Pugliese, Daniela
    IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
    Maharshak, Nitsan
    Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Cremer, Anneline
    Department of Gastroenterology, Erasme University Hopital, Brussels, Belgium.
    Limdi, Jimmy K.
    Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester, UK; Manchester Academic Health Sciences, University of Manchester, Manchester, UK.
    Molnár, Tamás
    First Department of Medicine, University of Szeged, Szeged, Hungary.
    Otero-Alvarin, Borja
    IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago, Spain.
    Krznaric, Zeljko
    Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, Zagreb, Croatia.
    Magro, Fernando
    Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.
    Karmiris, Konstantinos
    Department of Gastroenterology, Venizeleion General Hospital, Heraklion, Crete, Greece.
    Raine, Tim
    Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK.
    Drobne, David
    University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
    Koutroubakis, Ioannis
    Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
    Chaparro, Maria
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain.
    Yanai, Henit
    IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Burisch, Johan
    Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
    Kopylov, Uri
    Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Effectiveness of Third-Class Biologic Treatment in Crohn's Disease: A Multi-Center Retrospective Cohort Study2021In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 10, no 13, article id 2914Article in journal (Refereed)
    Abstract [en]

    Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described.

    Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD.

    Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5).

    Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

  • 8.
    Almon, Ricardo
    et al.
    Örebro University, School of Health and Medical Sciences.
    Engfeldt, Peter
    Örebro University, School of Health and Medical Sciences.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Sjöström, Michael
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Prevalence and trends in adult-type hypolactasia in different age cohorts in Central Sweden diagnosed by genotyping for the adult-type hypolactasia-linked LCT -13910C > T mutation2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 2, p. 165-170Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adult-type hypolactasia (AtH) can be diagnosed by genotyping in addition to functional tests or intestinal biopsy. The aims of this study were to estimate the prevalence of AtH by genotyping and to investigate whether AtH prevalence has changed in Sweden during the 20th century. MATERIAL AND METHODS: Schoolchildren (n=690) born in 1983 and 1989, and elderly individuals (n=392) born between 1920 and 1932 were genotyped for AtH using Pyrosequencing technology. RESULTS: The overall prevalence of AtH among children was 14.1%. The majority of children (92%, n=635) were Caucasians with genotype prevalences: CC, 61 (10%); CT, 259 (41%); TT, 307 (49%). The frequency of the mutated allele q was 0.300 in this cohort. The prevalence of AtH estimated from the Hardy-Weinberg equilibrium (HWE) (q 2), was 9.0% (95% CI: 6.7-11.2%). Eight percent (n=55) of the children were non-Caucasian; genotype prevalences were CC, 36 (66%); CT, 15 (27%); TT, 4 (7%). The prevalence of AtH in these children estimated from HWE was 62.5% (95% CI: 49.7-75.3%). The elderly subjects were all Caucasians. Their genotype prevalences were: CC, 20 (5%); CT, 166 (42%); TT, 206 (53%); the frequency of the mutated allele q was 0.262 and their AtH prevalence estimated from HWE was 6.8% (95% CI: 4.3-9.2%). CONCLUSIONS: The overall prevalence of AtH in children (14%) was higher than previously thought. Among Caucasians, higher figures were seen in children than in the elderly (9% versus 6.8%). The prevalence thus seems to be increasing and this may be due to the immigration of both non-Caucasian and Caucasian groups with a higher prevalence of AtH.

  • 9.
    Alonso-Cotoner, Carmen
    et al.
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Passeig Vall d'Hebron, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain; CIBER de Enfermedades Hepaticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain.
    Abril-Gil, Mar
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Albert-Bayo, Mercé
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Ganda Mall, John Peter
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Expósito, Elba
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    González-Castro, Ana M.
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Lobo, Beatriz
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Passeig Vall d'Hebron, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain.
    Santos, Javier
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain; CIBER de Enfermedades Hepaticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain.
    The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults2021In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 38, no 5, p. 2054-2076Article, review/survey (Refereed)
    Abstract [en]

    Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier. 

  • 10. Amcoff, K.
    et al.
    Joossens, M.
    Pierik, M. J.
    Jonkers, D.
    Bohr, J.
    Joossens, S
    Romberg-Camp, M.
    Nyhlin, Nils
    Wickbom, A.
    Rutgeerts, P. J.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bodin, L.
    Colombel, J. F.
    Vermeire, S.
    Halfvarson, Jonas
    Arvets inverkan på serologiska markörer hos tvillingar med IBD2012In: Gastrokuriren, ISSN 1651-0453, Vol. 17, no 26, p. MP-06-MP-06Article in journal (Other academic)
  • 11.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Lampinen, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S181-S182Article in journal (Other academic)
  • 12.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Lampinen, Maria
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 10, p. 1237-1244Article in journal (Refereed)
    Abstract [en]

    Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

    Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

    Methods: Patients with Crohn's disease (n=49) and ulcerative colitis (n=55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

    Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

    Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

  • 13. Amcoff, Karin
    et al.
    Joossens, Marie
    Pierik, Marie J.
    Jonkers, Daisy
    Bohr, Johan
    Joossens, Sofie
    Romberg-Camps, Marielle
    Nyhlin, Nils
    Wickbom, Anna K.
    Rutgeerts, Paul J.
    Tysk, Curt
    Bodin, Lennart
    Colombel, Jean-Frederic
    Vermeire, Severine
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Influence of genetics in the expression of serological markers in twins with IBD2012In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 5, p. S881-S881Article in journal (Other academic)
  • 14.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit, Leuven,Belgium; VIB Center for the Biology of Disease, Leuven, Belgium; Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit, Brussels, Belgium.
    Pierik, Marie J.
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Jonkers, Daisy
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Sofie
    Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
    Romberg-Camps, Mariëlle
    Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Colombel, Jean-Frederic
    Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Vermeire, Severine
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

  • 15.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Örebro University Hospital, Örebro, sweden.
    Stridsberg, Mats
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Lampinen, Maria
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Magnuson, Anders
    linical EpiSchool of Medical Sciences, Örebro University, Örebro, Sweden.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

    Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

    Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

    Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 16.
    Andersen, Vibeke
    et al.
    Medical Department, Sygehus Sønderjylland Aabenraa, Aabenraa, Denmark; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Vogel, Ulla
    National Research Centre for the Working Environment, Copenhagen, Denmark.
    Colorectal cancer in patients with inflammatory bowel disease: can we predict risk?2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 31, p. 4091-4094Article in journal (Refereed)
    Abstract [en]

    The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.

  • 17.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Inflammatory biomarkers in serum discriminate Crohn's disease and ulcerative colitis from healthy controls2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no Suppl. 1, p. S86-S87Article in journal (Other academic)
  • 18.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Neumann, Gunter
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE Basque Foundation for Science, Bilbao, Spain.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186142Article in journal (Refereed)
    Abstract [en]

    Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.

    Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.

    Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.

    Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.

  • 19.
    Angelison, L.
    et al.
    Helsingborg, Sweden.
    Almer, S.
    Stockholm, Sweden.
    Eriksson, A.
    Gothenburg, Sweden.
    Karling, P.
    Umeå, Sweden.
    Fagerberg, U.
    Västeras, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Thörn, M.
    Uppsala, Sweden.
    Björk, J.
    Stockholm, Sweden.
    Hindorf, U.
    Lund, Sweden.
    Löfberg, R.
    Stockholm, Sweden.
    Bajor, A.
    Gothenburg, Sweden.
    Hjortswang, H.
    Linköping, Sweden.
    Hammarlund, P.
    Ängelholm, Sweden.
    Grip, O.
    Malmö, Sweden.
    Torp, J.
    Kristianstad, Sweden.
    Marsal, J.
    Lund, Sweden.
    Hertervig, E.
    Lund, Sweden.
    Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 4, p. 519-532Article in journal (Refereed)
    Abstract [en]

    Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.

    Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.

    Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.

    Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.

    Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

  • 20.
    Anstee, Quentin M.
    et al.
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
    Darlay, Rebecca
    Population & Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Cockell, Simon
    Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Meroni, Marica
    Department of Pathophysiology and Transplantation, University of Milan, Translational Medicine - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
    Govaere, Olivier
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Tiniakos, Dina
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Dept of Pathology, Aretaieio Hospital, National & Kapodistrian University of Athens, Greece.
    Burt, Alastair D.
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia.
    Bedossa, Pierre
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Palmer, Jeremy
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Liu, Yang-Lin
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Aithal, Guruprasad P.
    NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
    Allison, Michael
    Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University NHS Foundation Trust, United Kingdom.
    Yki-Järvinen, Hannele
    Department of Medicine, University of Helsinki, Helsinki, Finland & Helsinki University Hospital, Helsinki, Finland.
    Vacca, Michele
    Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University NHS Foundation Trust, United Kingdom; Department of Biochemistry and Wellcome Trust/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, UK.
    Dufour, Jean-Francois
    University Clinic for Visceral Surgery and Medicine, University of Berne, Freiburgstrasse, Berne, Switzerland.
    Invernizzi, Pietro
    Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
    Prati, Daniele
    Department of Pathophysiology and Transplantation, University of Milan, Translational Medicine - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
    Ekstedt, Mattias
    Division of Gastroenterology and Hepatology, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
    Kechagias, Stergios
    Division of Gastroenterology and Hepatology, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
    Francque, Sven
    Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
    Petta, Salvatore
    Sezione di Gastroenterologia, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", Università di Palermo, Palermo, Italy.
    Bugianesi, Elisabetta
    Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
    Clement, Karine
    Sorbonne University, Inserm, Nutrition and obesity: Systemic approaches, Nutrition department, Pitié-Salpêtrière hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
    Ratziu, Vlad
    Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
    Schattenberg, Jörn M.
    NAFLD Research Center, Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
    Valenti, Luca
    Department of Pathophysiology and Transplantation, University of Milan, Translational Medicine - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
    Day, Christopher P.
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Cordell, Heather J.
    Population & Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Daly, Ann K.
    Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    EPoS, Consortium Investigators
    Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically-characterised cohort2020In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 73, no 3, p. 505-515Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Genetic factors associated with non-alcoholic fatty liver disease (NAFLD) remain incompletely understood. To date, most GWAS studies have adopted radiologically assessed hepatic triglyceride content as reference phenotype and so cannot address steatohepatitis or fibrosis. We describe a genome-wide association study (GWAS) encompassing the full spectrum of histologically characterized NAFLD.

    METHODS: The GWAS involved 1483 European NAFLD cases and 17781 genetically-matched population controls. A replication cohort of 559 NAFLD cases and 945 controls was genotyped to confirm signals showing genome-wide or close to genome-wide significance.

    RESULTS: Case-control analysis identified signals showing p-values ≤ 5 x 10-8 at four locations (chromosome (chr) 2 GCKR/C2ORF16; chr4 HSD17B13; chr19 TM6SF2; chr22 PNPLA3) together with two other signals with p<1 x10-7 (chr1 near LEPR and chr8 near IDO2/TC1). Case-only analysis of quantitative traits steatosis, disease activity score, NAS and fibrosis showed that the PNPLA3 signal (rs738409) was genome-wide significantly associated with steatosis, fibrosis and NAS score and identified a new signal (PYGO1 rs62021874) with close to genome-wide significance for steatosis (p=8.2 x 10-8). Subgroup case-control analysis for NASH confirmed the PNPLA3 signal. The chr1 LEPR SNP also showed genome-wide significance for this phenotype. Considering the subgroup with advanced fibrosis (≥F3), the signals on chromosomes 2, 19 and 22 remained genome-wide significant. With the exception of GCKR/C2ORF16, the genome-wide significant signals replicated.

    CONCLUSIONS: This study confirms PNPLA3 as a risk factor for the full histological spectrum of NAFLD at genome-wide significance levels, with important contributions from TM6SF2 and HSD17B13. PYGO1 is a novel steatosis modifier, suggesting relevance of Wnt signalling pathways in NAFLD pathogenesis.

  • 21.
    Assadi, Ghazaleh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden .
    Vesterlund, Liselotte
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Mazzurana, Luca
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Cordeddu, Lina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Schepis, Danika
    Rheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Mjösberg, Jenny
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden .
    Ruhrmann, Sabrina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fabbri, Alessia
    Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy .
    Vukojevic, Vladana
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Percipalle, Piergiorgio
    Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Salomons, Florian A.
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Laurencikiene, Jurga
    Lipid laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Törkvist, Leif
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden .
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain .
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.

    Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.

    Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.

    Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 22.
    Axelrad, J.
    et al.
    Department of Gastroenterology, New York University School of Medicine, New York, NY, USA.
    Olén, O.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Sachs, M.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Erichsen, R.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Pedersen, L.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, J.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Ekbom, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sørensen, H. T.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics.
    Inflammatory bowel disease and risk of small bowel cancer: A binational population-based cohort study from Denmark and Sweden2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no Suppl. 1, p. S007-S009Article in journal (Other academic)
  • 23.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, NYU Langone Health, New York NY, USA; Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York NY, USA.
    Olén, Ola
    Sachs’ Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Askling, Johan
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Lebwohl, Benjamin
    Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York NY, USA.
    Khalili, Hamed
    Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA.
    Sachs, Michael C.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
    Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study2019In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 17, no 7, p. 1311-1322Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC).

    METHODS: Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (control subjects). We then identified patients and control subjects with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection.

    RESULTS: Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to control subjects. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, C difficile, amoeba, or norovirus compared to control subjects. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis remained associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33).

    CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.

  • 24.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA .
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 2, p. 297-308Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).

    DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).

    RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).

    CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

  • 25.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Reply: Survival in Crohn's disease-associated small bowel adenocarcinoma2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 5, p. 998-998Article in journal (Refereed)
  • 26.
    Axelrad, Jordan E.
    et al.
    Division of Gastroenterology, Department of Medicine, NYU School of Medicine, New York NY, USA.
    Sachs, Michael C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs’ Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    A Novel Method for Quantifying Intestinal Inflammatory Burden in Inflammatory Bowel Disease Using Register Data2020In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 12, p. 1059-1072Article in journal (Refereed)
    Abstract [en]

    Background: The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization.

    Methods: In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization.

    Results: We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034).

    Conclusion: Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies.

  • 27.
    Axelrad, Jordan
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, NYU School of Medicine, New York, New York, USA.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Hamed
    Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
    Song, Mingyang
    Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
    Faye, Adam
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, NYU School of Medicine, New York, New York, USA.
    Eberhardson, Michael
    Department of Gastroenterology and Hepatology, Linköping University Hospital, Linköping University, Linköping, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
    Inflammatory Bowel Disease and Risk of Colorectal Polyps: A nationwide population-based cohort study from Sweden2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 9, p. 1395-1409Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inflammatory bowel disease (IBD) has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear.

    METHODS: We identified 41,880 individuals with IBD [Crohn's disease (CD: n=12,850); Ulcerative colitis (UC): n=29,030)] from Sweden matched with 41,880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios (aHRs) for neoplastic colorectal polyps (Tubular, Serrated/Sessile, Advanced and Villous) defined by histopathology codes.

    RESULTS: During follow-up, 1648 (3.9%) IBD patients and 1143 (2.7%) reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10,000 person-years, respectively. This correlated to an aHR of 1.23 (95% CI 1.12-1.35) with the highest HRs seen for sessile serrated polyps (8.50, 95% CI 1.10-65.90) and traditional serrated adenomas (1.72, 95% CI 1.02-2.91). aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and after 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD (aHRs 1.31 vs. 1.06, respectively), with a 20-year cumulative risk differences of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis.

    CONCLUSIONS: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.

  • 28.
    Axelsson, Erland
    et al.
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Liljeholmen Primary Health Care Center, Region Stockholm, Stockholm, Sweden; Academic Primary Health Care Center, Region Stockholm, Stockholm, Sweden.
    Kern, Dorian
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Hedman-Lagerlöf, Erik
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lindfors, Perjohan
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Palmgren, Josefin
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hesser, Hugo
    Örebro University, School of Behavioural, Social and Legal Sciences. Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
    Andersson, Erik
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Robert
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Olén, Ola
    Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children's Hospital, Stockholm, Sweden.
    Bonnert, Marianne
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Lalouni, Maria
    Division of Neuro, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Ljótsson, Brjánn
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Psychological treatments for irritable bowel syndrome: a comprehensive systematic review and meta-analysis2023In: Cognitive Behaviour Therapy, ISSN 1650-6073, E-ISSN 1651-2316, Vol. 52, no 6, p. 565-584Article, review/survey (Refereed)
    Abstract [en]

    A wide range of psychological treatments have been found to reduce the symptoms of irritable bowel syndrome (IBS) but their relative effects are unclear. In this systematic review and meta-analysis, we determined the effects of psychological treatments for IBS, including subtypes of cognitive behavior therapy, versus attention controls. We searched 11 databases (March 2022) for studies of psychological treatments for IBS, reported in journal articles, books, dissertations, and conference abstracts. The resulting database comprised 9 outcome domains from 118 studies published in 1983-2022. Using data from 62 studies and 6496 participants, we estimated the effect of treatment type on improvement in composite IBS severity using random-effects meta-regression. In comparison with the attention controls, there was a significant added effect of exposure therapy (g = 0.52, 95% CI = 0.17-0.88) and hypnotherapy (g = 0.36, 95% CI = 0.06-0.67) when controlling for the pre- to post-assessment duration. When additional potential confounders were included, exposure therapy but not hypnotherapy retained a significant added effect. Effects were also larger with a longer duration, individual treatment, questionnaire (non-diary) outcomes, and recruitment outside of routine care. Heterogeneity was substantial. Tentatively, exposure therapy appears to be a particularly promising treatment for IBS. More direct comparisons in randomized controlled trials are needed. OSF.io identifier: 5yh9a.

  • 29.
    Baunwall, Simon Mark Dahl
    et al.
    Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Terveer, Elisabeth M.
    Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, the Netherlands.
    Dahlerup, Jens Frederik
    Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Erikstrup, Christian
    Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
    Arkkila, Perttu
    Department of Gastroenterology, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
    Vehreschild, Maria Jgt
    Department of Internal Medicine II, Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany; ESCMID Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland; Department I of Internal Medicine, University of Cologne, Cologne, Germany; German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Germany.
    Ianiro, Gianluca
    Digestive Disease Center, CEMAD, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
    Gasbarrini, Antonio
    Digestive Disease Center, CEMAD, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
    Sokol, Harry
    Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Paris, France; INRA, UMR1319 Micalis, AgroParisTech, Jouy-en-Josas, France; French Group of Faecal Microbiota Transplantation (GFTF), Paris, France.
    Kump, Patrizia K.
    Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
    Satokari, Reetta
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    De Looze, Danny
    Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
    Vermeire, Séverine
    Department Gastroenterology and Hepatology, KU Leuven University Hospitals Leuven & KU Leuven, Belgium.
    Nakov, Radislav
    Clinic of Gastroenterology, Tsaritsa Yoanna University Hospital, Sofia, Bulgaria.
    Brezina, Jan
    Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
    Helms, Morten
    Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, Denmark.
    Kjeldsen, Jens
    Department of Medical Gastroenterology, Odense University Hospital Research Unit of Medical Gastroenterology, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
    Rode, Anne A.
    Department of Medicine, Zealand University Hospital, Køge, Denmark.
    Kousgaard, Sabrina Just
    Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.
    Alric, Laurent
    Department of Internal Medicine and Digestive Diseases, IRD Toulouse 3 University, Toulouse, France.
    Trang-Poisson, Caroline
    Gastroenterology Department, Institut des maladies de l'Appareil Digestif (IMAD), Centre d'investigation Clinique IMAD, University Hospital, Hotel-Dieu, Nantes, France.
    Scanzi, Julien
    French Group of Faecal Microbiota Transplantation (GFTF), Paris, France; Gastroenterology Department, Centre Hospitalier de Thiers, Thiers, France.
    Link, Alexander
    Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
    Stallmach, Andreas
    Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany.
    Kupcinskas, Juozas
    Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Johnsen, Peter Holger
    University Hospital of North Norway Harstad, Harstad, Norway.
    Garborg, Kjetil
    Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Health and Society, University of Oslo, Oslo, Norway.
    Rodríguez, Eugenia Sánchez
    Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
    Serrander, Lena
    Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Galpérine, Katerina Tatiana
    French Group of Faecal Microbiota Transplantation (GFTF), Paris, France; Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
    Goldenberg, Simon D.
    Centre for Clinical Infection and Diagnostics Research (CIDR), King's College London and Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
    Mullish, Benjamin H.
    Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.
    Williams, Horace Rt.
    Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom.
    Iqbal, Tariq H.
    Department of Gastroenterology, Institute of Immunology and Immunotherapy, University of Birmingham, University Hospital, Birmingham, United Kingdom.
    Ponsioen, Cyriel
    Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
    Kuijper, Ed J.
    Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, the Netherlands; ESCMID Study Group for Host and Microbiota Interaction (ESGHAMI), Basel, Switzerland; Centre for Microbiota Analysis and Therapeutics, Leiden University Medical Centre, Leiden, the Netherlands; National Reference Laboratory for Clostridium difficile, Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands; National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
    Cammarota, Giovanni
    Digestive Disease Center, CEMAD, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
    Keller, Josbert J.
    Netherlands Donor Feces Bank, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastroenterology, Haaglanden Medical Center, The Hague, the Netherlands; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
    Hvas, Christian Lodberg
    Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey2021In: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 9, article id 100181Article in journal (Refereed)
    Abstract [en]

    Background: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.

    Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.

    Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.

    Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.

    Funding: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

  • 30.
    Bazov, Igor
    et al.
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Hedin, C. R.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska University Hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Carlson, M.
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    van Nieuwenhoven, Michiel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Keita, Å. V.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Magnusson, M. K.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Almer, S.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska university hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Strid, H.
    Södra Älvsborgs Hospital, Department of Internal Medicine, Borås, Sweden.
    Mathisen, C. Bache-Wiig
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Bengtsson, M. B.
    Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Aabrekk, T. Bergene
    University of Oslo, Institute of Clinical Medicine, Oslo, Norway; Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Medhus, A. W.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Detlie, T. E.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; University of Oslo, Insititute of Clinical Medicine, Oslo, Norway.
    Frigstad, S. O.
    Vestre Viken Hospital Trust- Bærum Hospital, Department of Internal Medicine, Bærum, Norway.
    Huppertz-Hauss, G.
    Telemark Hospital Trust, Skien, Department of Gastroenterology, Skien, Norway.
    Opheim, R.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Health and Society, Oslo, Norway.
    Ricanek, P.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; Lovisenberg Diaconal Hospital, Department of Gastroenterology, Oslo, Norway.
    Kristensen, V. A.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway .
    Salihovic, Samira
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Karolinska Institutet, Clinical Epidemiology Division, Department of Medicine Solna, Stockholm, Sweden; IKERBASQUE, Basque Foundation for Science, Bilbao, Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Bilbao, Spain.
    Öhman, L.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Söderholm, J. D.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Lindqvist, C. M.
    Örebro University, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Høivik, M. L.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I314-I315, article id P154Article in journal (Other academic)
  • 31.
    Bednarska, Olga
    et al.
    Department of Gastroenterology, Linköping University Hospital, Linköping, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Schmidt, Peter Thelin
    Department of Medicine, Ersta Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Solna, Sweden.
    Johansson, Gabriele Wurm
    Department of Gastroenterology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Toth, Ervin
    Department of Gastroenterology, Skåne University Hospital, Lund University, Malmö, Sweden.
    Lindfors, Perjohan
    Department of Clinical Neuroscience, Division of Psychology, Karolinska Institutet, Solna, Sweden; Aleris Gastromottagningen City, Stockholm, Sweden.
    The Effectiveness and Tolerability of a Very Low-Volume Bowel Preparation for Colonoscopy Compared to Low and High-Volume Polyethylene Glycol-Solutions in the Real-Life Setting2022In: Diagnostics, ISSN 2075-4418, Vol. 12, no 5, article id 1155Article in journal (Refereed)
    Abstract [en]

    Adequate bowel cleansing is essential for high-quality colonoscopy. Recently, a new very low-volume 1 litre (1L) polyethylene glycol (PEG) plus ascorbate solution (ASC) has been introduced. Our aims were to assess the effectiveness and tolerability of this product compared to low-volume 2L PEG-ASC and high-volume 4L PEG solutions, in a real-life setting. In six endoscopy units in Sweden, outpatients undergoing colonoscopy were either prescribed solutions according to local routines, or the very low-volume solution in split dose regimen. Bowel cleansing effectiveness and patient experience was assessed using the Boston Bowel preparation scale (BBPS) and a patient questionnaire. A total of 1098 patients (mean age 58 years, 52% women) were included. All subsegment and the total BBPS scores were significantly greater for 1L PEG-ASC in comparison to other solutions (p < 0.05 for 1L PEG-ASC and 4L PEG for transverse and left colon, otherwise p < 0.001). Nausea was more frequent with 1L PEG-ASC compared to 2L PEG-ASC (p < 0.001) and vomiting were more often reported compared to both other solutions (p < 0.01 and p < 0.05 for 2L PEG-ASC and 4L PEG, respectively). Smell, taste, and total experience was better for 1L PEG-ASC compared to 4L PEG (p < 0.001), and similar compared to the 2L PEG-ASC. In conclusion, 1L PEG-ASC leads to better bowel cleansing compared to 2L PEG-ASC or 4L PEG products, with similar or greater patient satisfaction.

  • 32.
    Bengtsson, Bonnie
    et al.
    Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Unit of Gastroenterology andnRheumatology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Askling, Johan
    Rheumatology, Theme Inflammation and Infection, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Hagström, Hannes
    Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Unit of Gastroenterology andnRheumatology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Validity of administrative codes associated with cirrhosis in Sweden2020In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 55, no 10, p. 1205-1210Article in journal (Refereed)
    Abstract [en]

    Objectives: Although cirrhosisis a major cause of liver-related mortality globally, validation studies of the administrative coding for diagnoses associated with cirrhosis are scarce. We aimed to determine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes corresponding to cirrhosis and its complications in the Swedish National Patient Register (NPR).

    Methods: We randomly selected 750 patients with ICD codes for either alcohol-related cirrhosis (K70.3), unspecified cirrhosis (K74.6) oesophageal varices (I85.0/I85.9), hepatocellular carcinoma (HCC, C22.0) or ascites (R18.9) registered in the NPR from 72 healthcare centres in 2000-2016. Hospitalisation events and outpatient visits in specialised care were included. Positive predictive values (PPVs) were calculated using the information in the patient charts as the gold standard.

    Results: Complete data were obtained for 630 (of 750) patients (84%). For alcohol-related cirrhosis, 126/136 cases were correctly coded, corresponding to a PPV of 93% (95% confidence interval, 95%CI: 87-96). The PPV for cirrhosis with unspecified aetiology was 91% (121/133, 95%CI: 85-95) and 96% for oesophageal varices (118/123, 95%CI: 91-99). The PPV was lower for HCC, 84% (91/109, 95%CI: 75-90). The PPV for liver-related ascites was low, 43% (56/129, 95%CI: 35-52), as this category often consisted of non-hepatic ascites. When combining the ascites code with a code for chronic liver disease, the PPV for liver-related ascites increased to 93% (50/54, 95%CI: 82-98).

    Conclusions: The validity of ICD-10 codes for cirrhosis, oesophageal varices and HCC is high. However, coding for ascites should be combined with a code of chronic liver disease to have an acceptable validity.

  • 33.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Andersson, Erik
    Örebro University, School of Medical Sciences. Department of Gastroenterolog.
    Hultdin, Johan
    Department of Medical Biosciences, Division of Clinical Chemistry, Umeå University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Rush, Stephen T.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kalla, Rahul
    MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Adams, Alex T.
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
    Keita, Åsa V.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    D'Amato, Mauro
    CIC bioGUNE Basque Research and Technology Alliance, BRTA and IKERBASQUE, Basque Science Foundation, Bilbao, Spain; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Gomollon, Fernando
    HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain.
    Jahnsen, Jorgen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Ricanek, Petr
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    Satsangi, Jack
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Systemic Inflammation in Preclinical Ulcerative Colitis2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. 1526-1539.e9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Pre-clinical ulcerative colitis is poorly defined. We aimed to characterize the pre-clinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.

    METHODS: We obtained plasma samples, biobanked from individuals who later in life developed ulcerative colitis (n=72), and matched healthy controls (n=140), within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biological relevance of these findings were validated in an inception cohort of ulcerative colitis patients (n=101), and healthy controls (n=50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of ulcerative colitis patients (n=41) and matched healthy controls (n=37) were explored.

    RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP1) were upregulated (p<0.05) in pre-clinical ulcerative colitis compared to controls based on both univariate and mulativariable models. Ingenuity Pathway Analyses identified several potential key regulators, including IL-1b, TNF, IFN-gamma, OSM, NFĸB, IL-6 and IL-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve ulcerative colitis patients from controls with leave-one-out cross-validation (AUC=0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly upregulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.

    CONCLUSIONS: A set of inflammatory proteins are upregulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be upregulated already at exposure to genetic and environmental risk factors.

  • 34.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences.
    Andersson, Erik
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umea University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hultdin, Johan
    Medical Biosciences, Clinical Chemistry, Umea University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    IBD Character Consortium,
    Markers of systemic inflammation in preclinical ulcerative colitis2019In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 7, no 8_suppl, p. 111-111Article in journal (Refereed)
    Abstract [en]

    Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.

    Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.

    Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.

    Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.

  • 35.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sapnara, Maria
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Elevated fecal peptidase D at onset of colitis in Galphai2(-/-) mice, a mouse model of IBD2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174275Article in journal (Refereed)
    Abstract [en]

    Background: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms.

    Methods: Fecal samples were collected at onset of inflammation in Galphai2(-/-) mice, a well-described spontaneous model of chronic colitis, and from healthy littermates. The fecal proteome was analyzed by two-dimensional electrophoresis and quantitative mass spectrometry and results were then validated in a new cohort of mice.

    Results: As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai24mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gai2(-/-) mice were mainly pancreatic proteases, and proteins from plasma and blood cells. A tendency of increased calprotectin, subunit S100-A8, was also observed (fold change 21; p = 0.058). Proteases are potential activators of inflammation in the gastrointestinal tract through their interaction with the proteinase-activated receptor 2 (PAR2). Accordingly, the level of PAR2 was found to be elevated in both the colon and the pancreas of Galphai24- mice at different stages of disease.

    Conclusions: These findings identify peptidase D, an ubiquitously expressed intracellular peptidase, as a potential novel marker of colitis. The elevated levels of fecal proteases may be involved in the pathogenesis of colitis and contribute to the clinical phenotype, possibly by activation of intestinal PAR2.

  • 36.
    Bergman, David
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Brommaplans Primary Health Care Center, Stockholm, Sweden.
    Clemente, Mark S.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Flamed
    Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA; Harvard Medical School, Boston Massachusetts, USA.
    Agréus, Lars
    Division for Family Medicine and Primary Care, Karolinska Institutet, Huddinge, Sweden.
    Hultcrantz, Rolf
    Unit of Hepatology, Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    A nationwide cohort study of the incidence of microscopic colitis in Sweden2019In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 49, no 11, p. 1395-1400Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies of microscopic colitis have shown varying but increasing incidence rates. Aim To assess the incidence of microscopic colitis in Sweden.

    Methods: Nationwide cohort study performed in 1995-2015 based on biopsy reports. Age-specific and age-standardised incidence rates were calculated.

    Results: We identified 13 844 patients with an incident diagnosis of microscopic colitis. Lymphocytic colitis (n = 9238) constituted 67% and collagenous colitis (n = 4606) 33% of microscopic colitis. The mean age at time of diagnosis of microscopic colitis was 60.2 years (58.6 for lymphocytic colitis, 63.3 for collagenous colitis). The lifetime risk of developing microscopic colitis was 0.87% in women (95% confidence interval, CI: 0.85-0.88) and 0.35% in men (95% CI: 0.34-0.36). From 2006, the overall incidence of microscopic colitis was approximately 10.5 cases per 100 000 person-years (95% CI: 9.8-11.3) with higher rates in women (72% of cases, incidence rate ratio = 2.4 (95% CI: 2.3-2.5) and the elderly with increasing rates up to 75-79 years. From 2006-2015, there was a significant increase of 1% per year (P = 0.02) in the overall microscopic colitis incidence rate in women; the estimated annual percent change was similar, although not statistically significant, in men (P = 0.15).

    Conclusions: In Sweden, the incidence of microscopic colitis is still increasing in women, although the rate appears to be stabilising. The incidence is particularly high in women and the elderly up to age 75-79 years. Finally, across a lifetime, 1 in 115 females and 1 in 286 males are expected to be diagnosed with microscopic colitis and thus posing a considerable disease burden.

  • 37.
    Bergman, David
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Hamed
    Massachusetts General Hospital, Crohn’s and Colitis Center and Harvard Medical School, Boston MA, USA; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Microscopic Colitis and Risk Of Cancer-AA Population-Based Cohort Study2021In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 15, no 2, p. 212-221Article in journal (Refereed)
    Abstract [en]

    Background and Aims: The association between microscopic colitis [MC] and cancer risk is unclear. Large, population-based studies are lacking.

    Methods: We conducted a nationwide cohort study of 11 758 patients with incident MC [diagnosed 1990-2016 in Sweden], 50 828 matched reference individuals, and 11 614 siblings to MC patients. Data were obtained through Sweden's pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios [aHRs] were calculated using Cox proportional hazards models.

    Results: At the end of follow-up [mean: 6.7 years], 1239 [10.5%] of MC patients had received a cancer diagnosis, compared with 4815 [9.5%] of reference individuals (aHR 1.08 [95% confidence interval1.02-1.16]). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10, and 20 years after MC diagnosis were + 1.0% (95% confidence interval [C1]0.4%-1.6%), +1.5% [0.4%-2.6%], and + 3.7% [-2.3-9.6%], respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for 10 years. MC was associated with an increased risk of lymphoma (aHR 1.43 [1.06-1.92]) and lung cancer (aHR 1.32 [1.04-1.68]) but with decreased risks of colorectal (aHR 0.52 [0.40-0.66]) and gastrointestinal cancers (aHR 0.72 [0.60-0.85]). We found no association with breast or bladder cancer. Using siblings as reference group to minimise the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR 1.20 [1.06-1.36]).

    Conclusions: This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow-up.

  • 38.
    Bergman, David
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Brommaplans Primary Health Care Center, Stockholm County, Stockholm, Sweden.
    King, James
    Centre for health informatics, University of Calgary Cumming School of Medicine, Calgary Alberta, Canada.
    Lebwohl, Benjamin
    Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Clements, Mark S.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Kaplan, Gilaad G.
    Department of Medicine, University of Calgary, Calgary Alberta, Canada.
    Green, Peter Hr
    Department of Medicine, Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Murray, Joseph A.
    Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester Minnesota, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 20152022In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 71, no 6, p. 1088-1094Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation.

    Design: Nationwide population-based cohort study 1990-2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum.

    Results: We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002-2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males). Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa.

    Conclusions: In Sweden, the incidence of CD increased until 2002-2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.

  • 39.
    Bergquist, Annika M.
    et al.
    Karolinska University Hospital, Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Huddinge, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Lenzen, Henrike
    Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany; University Hospital Essen, University of Duisburg-Essen, Department of Gastroenterology and Hepatology, Essen, Germany.
    Hepatobiliary malignancy surveillance strategies in primary sclerosing cholangitis associate with reduced mortality2021In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 75, no Suppl. 2, p. S227-S228Article in journal (Other academic)
    Abstract [en]

    Background and aims: Patients with primary sclerosing cholangitis (PSC) are at increased risk for hepatobiliary malignancies, especially cholangiocarcinoma. Although many recommend surveillance for malignancy in PSC, different strategies are used by various centers and countries. We aimed to evaluate different surveillance strategies and their effectiveness in PSC with the hypothesis that surveillance imaging improves survival.

    Method: We queried centers about surveillance practices and retrospectively collected imaging surveillance data for hepatobiliary cancer in 2, 975 patients with PSC from 28 centers within the International PSC Study Group (IPSCSG). Surveillance strategies were grouped in (i) non-surveillance (no imaging in asymptomatic patients), (ii) magnetic resonance imaging (MRI) and/or ultrasound (US) surveillance (regular imaging regardless of symptoms/labs) and (iii) surveillance including endoscopic retrograde cholangiopancreatography (ERCP)-based (imaging and/or ERCP regardless of symptoms/labs). The primary end point was all-cause mortality. Cox-proportional hazard regression models were used to estimate hazard ratios (HRs).

    Results: 65.6% (1953/2975) of patients were male, mean age (SD) at diagnosis of PSC was 35.6 (14.2) years, with concomitant IBD in 71.5% (2127/2973). Hepatobiliary malignancy was found in 175 (5.9%) patients at 7.9 years of follow-up (Figure). Surveillance strategies differed significantly between centers. Of patients undergoing surveillance, 83% were subjected to MRI/MRCP, 49% to US and 28% to ERCP. Deaths were more frequent in the non-surveillance group 23.4% (82/350) than in the surveillance group 8.3% (218/2625). Mortality rate (95% CI) per 1000 person-years was 23.1 (18.1–28.1) inthe non-surveillance group (n = 350), 12.5 (10.6–14.5) in imaging surveillance with MRI and/or US (n = 1897) and 8.4 (6.3–10.5) in surveillance that included ERCP (n = 728). The risk of dying wasr educed in patients undergoing any type of surveillance (HR 0.53; 95% CI: 0.41–0.68) and the reduced risk remained after adjusting for sex, age and start year of follow-up (HR 0.61; 95% CI: 0.47–0.80).

    Conclusion: A broad variety of surveillance strategies across centers are used. Regular sur veillance for hepatobiliary malignancy in patients with PSC is associated with improved survival.

  • 40. Bergquist, Annika
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Bahmanyar, Shahram
    Olsson, Rolf
    Danielsson, Åke
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Lööf, Lars
    Sandberg-Gertzén, Hanna
    Almer, Sven
    Askling, Johan
    Ehlin, Anna
    Ekbom, Anders
    Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis2008In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 6, no 8, p. 939-943Article in journal (Refereed)
    Abstract [en]

    Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6–84.4), 11.1 (3.3–37.8), and 2.3 (0.9–6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3–4.9) and for Crohn's disease 1.4 (0.8–2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9–18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC. 

  • 41. Bergquist, Annika
    et al.
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Lund, Ulrika
    Ekbom, Anders
    Olsson, Rolf
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Broomé, Ulrika
    Perinatal events and the risk of developing primary sclerosing cholangitis2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 37, p. 6037-6040Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether perinatal events, intrauterine or postpartum, are associated with the development of primary sclerosing cholangitis (PSC) later in life.

    METHODS: Birth records from 97 patients with adult PSC in Sweden were reviewed. Information on perinatal events including medications and complications during pregnancy, gestation length, birth weight and length were collected. Two control children of the same sex were selected for each subject. Conditional multiple logistic regression was used to assess associations of the perinatal measures with development of PSC.

    RESULTS: No significant associations were found between gestational age, birth length, breastfeeding, and the majority of medical complications including infections or medication during pregnancy for the mothers or postpartum for the children. Vaginal bleeding and peripheral oedema showed associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and 2.28 (95% CI, 1.04-5.03), respectively.

     

    CONCLUSION: The associations of vaginal bleeding and oedema with subsequent PSC cannot readily be explained, so our findings do not strongly support the hypothesis of a significant role of perinatal events as a risk for the development of PSC later in life.

  • 42.
    Bergquist, Annika
    et al.
    Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases, Stockholm, Sweden.
    Weismüller, Tobias J.
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Levy, Cynthia
    Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA; Schiff Center for Liver Diseases, University of Miami, Miami, FL, USA.
    Rupp, Christian
    Department of Gastroenterology, Infectious Diseases, Intoxication, Heidelberg University Hospital, Heidelberg, Germany.
    Joshi, Deepak
    Institute of Liver Studies, King's College Hospital London, United Kingdom.
    Nayagam, Jeremy Shanika
    Institute of Liver Studies, King's College Hospital London, United Kingdom.
    Montano-Loza, Aldo J.
    Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Canada.
    Lytvyak, Ellina
    Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Canada.
    Wunsch, Ewa
    Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland.
    Milkiewicz, Piotr
    Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland; Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland .
    Zenouzi, Roman
    Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Schramm, Christoph
    Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Cazzagon, Nora
    Department of Surgery, Oncology and Gastroenterology, University of Padova, , Padova, Italy and European Reference Network on Hepatological Disease, European Reference Network for Hepatological Diseases, Azienda Ospedaliera-Università di Padova, Padova, Italy.
    Floreani, Annarosa
    Studiosa Senior University of Padova, Italy and Scientific Consultant IRCCS Negrar, Verona, Italy.
    Friis Liby, Ingalill
    Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Wiestler, Miriam
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany.
    Wedemeyer, Heiner
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany.
    Zhou, Taotao
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Strassburg, Christian P.
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Rigopoulou, Eirini
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
    Dalekos, George
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
    Narasimman, Manasa
    Schiff Center for Liver Diseases, University of Miami, Miami, FL, USA.
    Verhelst, Xavier
    Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium, Ghent Liver Research Center, Ghent University, Belgium; European Reference Network for Hepatological Diseases, Ghent, Belgium.
    Degroote, Helena
    Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium, Ghent Liver Research Center, Ghent University, Belgium; European Reference Network for Hepatological Diseases, Ghent, Belgium.
    Vesterhus, Mette
    Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
    Kremer, Andreas E
    Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany; Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
    Bündgens, Bennet
    Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Rorsman, Fredrik
    Department of Gastroenterology and Hepatology, University Hospital, Uppsala, Sweden.
    Nilsson, Emma
    Department of Clinical Sciences, Lund University, Lund, Sweden; Gastroenterology Clinic, Skåne University Hospital, Sweden.
    Jørgensen, Kristin Kaasen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    von Seth, Erik
    Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases, Stockholm, Sweden.
    Cornillet, Martin
    Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Martin, Harry
    Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, UK.
    Kechagias, Stergios
    Department of Health, Medicine and Caring Sciences, Unit of Internal Medicine, Linköping University, Linköping, Sweden.
    Wiencke, Kristine
    Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
    Werner, Mårten
    Department of Public Health and clinical medicine, Umeå University, Umeå, Sweden.
    Terziroli Beretta-Piccoli, Benedetta
    Epatocentro Ticino, Università della Svizzera Italiana, Lugano, Switzerland.
    Marzioni, Marco
    Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti - University Hospital, Ancona, Italy.
    Isoniemi, Helena
    Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
    Arola, Johanna
    Department of Pathology and Huslab, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Wefer, Agnes
    Division of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Färkkilä, Martti
    University of Helsinki and Helsinki University Hospital, Clinic of Gastroenterology, Abdominal Center, Helsinki, Finland.
    Lenzen, Henrike
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany .
    Impact on follow-up strategies in patients with primary sclerosing cholangitis2023In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 43, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.

    METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.

    RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.

    CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

  • 43.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Serrander, Lena
    Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Magnusson, Cecilia
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides Difficile, Clinical Microbiology.
    Bergman-Jungeström, Malin
    Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 4, article id e0249861Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.

    METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.

    RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).

    CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

  • 44.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Seifert, M.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Engstrand, L.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Increasing abundance of faecalibacterium prausnitzii is associated with decreased intestinal inflammation in Crohn's disease: A longitudinal study2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S468-S469Article in journal (Other academic)
  • 45.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Orebro Univ, Sch Med Sci, Orebro, Sweden..
    Seifert, Maike
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Brislawn, Colin
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Jansson, Janet
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn's disease: a longitudinal study2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 4, p. 577-585Article in journal (Refereed)
    Abstract [en]

    Objectives: Crohn's disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity.

    Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn's disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin.

    Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = -0.39; p = .009). Changes in C. leptum (R = -0.18, p = .23) and number of copies of the BCoAT gene (R = -0.12; p = .42) did not correlate with f-calprotectin.

    Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn's disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.

  • 46.
    Blach, Sarah
    et al.
    Ctr Dis Anal Fdn, Lafayette CO, USA.
    Duberg, Ann-Sofi
    Örebro University, School of Medical Sciences.
    Razavi, Homie A.
    Ctr Dis Anal Fdn, Lafayette CO, USA.
    Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study2022In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 7, no 5, p. 396-415Article in journal (Refereed)
    Abstract [en]

    Background: Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends.

    Methods: This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories.

    Findings: Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment.

    Interpretation: At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination.

  • 47.
    Bledsoe, Adam C.
    et al.
    Department of Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls SD, USA.
    Garber, John J.
    Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA.
    Ye, Weimin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Murray, Joseph A.
    Celiac Disease Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester MN, USA.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Clinical Sciences Building 2, City Hospital, Nottingham, UK; Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Mortality and cancer in eosinophilic gastrointestinal disorders distal to the esophagus: nationwide cohort study 1990-20172022In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 57, p. 735-747Article in journal (Refereed)
    Abstract [en]

    Background: Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus.

    Methods: Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden's all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education.

    Results: In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04-1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32-2.48, aHR = 1.50; 95%CI = 1.18-1.89, and aHR = 0.99; 95%CI = 0.85-1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05-1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96-1.35). Comparison of EGID individuals with their siblings yielded similar aHRs.

    Conclusions: This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers.

  • 48. Block, T.
    et al.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Björck, M.
    Acosta, S.
    Diagnostic accuracy of plasma biomarkers for intestinal ischaemia2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 3, p. 242-248Article in journal (Refereed)
    Abstract [en]

    Objective. Intestinal ischaemia is a life‐threatening condition with high mortality, and the lack of accurate and readily available diagnostic methods often results in delay in diagnosis and treatment. The aim of this study was to investigate the accuracy of different plasma biomarkers in diagnosing intestinal ischaemia. Material and methods. Prospective inclusion of patients older than 50 years with acute abdomen admitted to hospital in Karlskrona, Sweden, between 2001 and 2003. Venous blood was sampled prior to any surgery and within 24h from onset of pain. D‐lactate, alpha glutathione S‐transferase, intestinal fatty acid binding protein, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) were analysed. D‐dimer was analysed using four different commercially available test kits. Results. In‐hospital mortalities among patients with (n = 10) and without (n = 61) intestinal ischaemia were 40% and 3%, respectively (p = 0.003). D‐dimer was associated with intestinal ischaemia (p = 0.001) independently of which assay was used. No patient presenting with a normal D‐dimer had intestinal ischaemia. D‐dimer >0.9mg/L had a specificity, sensitivity and accuracy of 82%, 60% and 79%, respectively. Total LD, isoenzymes of LD 1–4 and liver isoenzyme of ALP (ALP liver) were significantly higher in patients with intestinal ischaemia, and accuracies for LD 2 (cut‐off 2.3µkat/L) and ALP liver (cut‐off 0.7µkat/L) were 69% and 66%, respectively. Conclusions. D‐dimer may be used as an exclusion test for intestinal ischaemia, but lacks specificity. The other plasma biomarkers studied had insufficient accuracy for this group of patients. Further studies are needed. 

  • 49. Blom, Kristin
    et al.
    Rubin, Jenny
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Intestinal Medicine, Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Rönnblom, Anders
    Sangfelt, Per
    Lördal, Mikael
    Jönsson, Ulla-Britt
    Sjöqvist, Urban
    Håkansson, Lena Douhan
    Venge, Per
    Carlson, Marie
    Eosinophil associated genes in the inflammatory bowel disease 4 region: correlation to inflammatory bowel disease revealed2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 44, p. 6409-6419Article in journal (Refereed)
    Abstract [en]

    AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).

    METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP(®) system as described by the manufacturer. Statistical tests for calculations of results were χ(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.

    RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.

    CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

  • 50.
    Bodea, Corneliu A.
    et al.
    Department of Statistics, Carnegie Mellon University, Pittsburgh PA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Neale, Benjamin M.
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge MA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Ripke, Stephan
    Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA; Department of Psychiatry and Psychotherapy, Charite, Campus Mitte, Berlin, Germany.
    International IBD Genetics Consortium, Group author
    Daly, Mark J.
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge MA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Devlin, Bernie
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
    Roeder, Kathryn
    Department of Statistics, Carnegie Mellon University, Pittsburgh PA, USA; Computational Biology Department, Carnegie Mellon University, Pittsburgh PA, USA.
    A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 98, no 5, p. 857-868Article in journal (Refereed)
    Abstract [en]

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.

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