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

Autor:	Weismüller TJ; Department of Internal Medicine I, University of Bonn, Germany; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: tobias.weismueller@gmx.de., Trivedi PJ; National Institute for Health Research (NIHR) Birmingham, Liver Biomedical Research Centre (BRC), University of Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham Queen Elizabeth, United Kingdom., Bergquist A; Center for Digestive Diseases, Division of Hepatology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden., Imam M; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Department of Internal Medicine, University of North Dakota, Grand Forks, North Dakota., Lenzen H; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Ponsioen CY; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands., Holm K; Norwegian PSC Research Center and Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Gotthardt D; Department of Gastroenterology, Infectious Diseases and Intoxications, University Hospital Heidelberg, Heidelberg, Germany., Färkkilä MA; Helsinki University, Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland., Marschall HU; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Thorburn D; The Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom., Weersma RK; Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center, Groningen, The Netherlands., Fevery J; Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium., Mueller T; Department of Internal Medicine, Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany., Chazouillères O; Service d'Hépatologie, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, Paris, France., Schulze K; 1st Department of Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Lazaridis KN; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota., Almer S; Division of Gastroenterology and Hepatology, Linköping University, Linköping; Sweden., Pereira SP; Institute for Liver and Digestive Health, University College London, London, United Kingdom., Levy C; Division of Hepatology, University of Miami, Miami, Florida., Mason A; Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, AB, Canada., Naess S; Norwegian PSC Research Center and Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Bowlus CL; Division of Gastroenterology and Hepatology, University of California Davis, Davis, California., Floreani A; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy., Halilbasic E; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria., Yimam KK; Department of Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco, California., Milkiewicz P; Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland; Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland., Beuers U; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands., Huynh DK; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia., Pares A; Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd, University of Barcelona, Spain., Manser CN; Division for Gastroenterology and Hepatology, University Hospital Zurich (USZ), Zurich, Switzerland., Dalekos GN; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa, Greece., Eksteen B; University of Calgary, Snyder Institute for Chronic Diseases, Alberta, AB, Canada., Invernizzi P; Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy., Berg CP; Department of Gastroenterology, Hepatology, and Infectiology, Medical Clinic, University of Tübingen, Germany., Kirchner GI; Department of Internal Medicine 1, University Hospital of Regensburg, Regensburg, Germany., Sarrazin C; Department of Internal Medicine 1, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany., Zimmer V; Department of Medicine II, Saarland University Medical Center, Homburg, Germany., Fabris L; Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy., Braun F; Department of General, Visceral, Thoracic, Transplantation and Pediatric Surgery, Campus Kiel, UKSH, Kiel, Germany., Marzioni M; Clinic of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy., Juran BD; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota., Said K; Center for Digestive Diseases, Division of Hepatology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden., Rupp C; Department of Gastroenterology, Infectious Diseases and Intoxications, University Hospital Heidelberg, Heidelberg, Germany., Jokelainen K; Helsinki University, Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland., Benito de Valle M; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Saffioti F; The Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom., Cheung A; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota., Trauner M; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria., Schramm C; 1st Department of Medicine, University Medical Center Hamburg Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Chapman RW; Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom., Karlsen TH; Norwegian PSC Research Center and Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Schrumpf E; Norwegian PSC Research Center and Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Strassburg CP; Department of Internal Medicine I, University of Bonn, Germany., Manns MP; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Lindor KD; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona; Arizona State University, College of Health Solutions, Phoenix, Arizona., Hirschfield GM; National Institute for Health Research (NIHR) Birmingham, Liver Biomedical Research Centre (BRC), University of Birmingham, United Kingdom., Hansen BE; Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada., Boberg KM; Norwegian PSC Research Center and Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: kboberg@ous-hf.no.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2017 Jun; Vol. 152 (8), pp. 1975-1984.e8. Date of Electronic Publication: 2017 Mar 06.
DOI:	10.1053/j.gastro.2017.02.038
Abstrakt:	Background & Aims: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. Methods: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 41-50 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P < .001 and HR, 0.90; P = .03, respectively) and malignancy (HR, 0.68; P = .008 and HR, 0.77; P = .004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P < .001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P = .002 and HR, 0.68; P < .001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P < .001 and adjusted HR for women, 0.48; P = .003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P < .001) or no IBD (HR, 1.15; P = .002). Conclusions: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials. (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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