title: Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study.
abstract: Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC) have not been firmly established. Enhanced liver fibrosis (ELF) test was previously reported to predict outcome in PSC. We aimed to validate the prognostic utility of ELF test in an independent, multi-centre, retrospective PSC study population.
  
  
  
  We collected serum samples from PSC patients from seven countries. We estimated rates of transplant-free survival by the Kaplan-Meier method, used Cox proportional hazards regression to explore the association between ELF test and clinical outcome and determined prognostic performance of ELF test by computing the area under the receiver operating characteristic (AUC-ROC) curve.
  
  
  
  The final analysis included 534 PSC patients (61% males). Features of autoimmune hepatitis or concomitant inflammatory bowel disease affected 44 (8%) and 379 (71%) patients respectively. ELF test levels were higher in patients reaching the combined endpoint liver transplantation or death (median 10.9 [Interquartile range (IQR): 9.8-12.1]; n=24 deaths, 79 liver transplantations) compared to those censored (8.8 [IQR: 8.0-9.8]); P<.001. ELF test expressed as mild, moderate and severe fibrosis was significantly associated with the risk of reaching the endpoint (P<.001). ELF test independently predicted clinical outcome (Hazard ratio 1.31; 95% confidence interval [1.05-1.65]; P=.018), and enabled good discrimination between PSC patients with and without endpoint (AUC-ROC: 0.79).
  
  
  
  Our retrospective data validates the predictive utility of ELF test for clinical outcomes in PSC. The clinical utility of biomarkers for fibrosis in patients with PSC should be assessed in prospective patient cohorts.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elisabeth M G
authors.initials: EMG
authors.lastname: de Vries
authors.affiliation: Clinic of Gastroenterology, Helsinki University Hospital, Helsinki University, Helsinki, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.affiliation: Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Milkiewicz
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Johannes R
authors.identifier: 0000-0002-5900-8096
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Snyder Institute of Chronic Diseases, Department of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Bertus
authors.initials: B
authors.lastname: Eksteen
authors.affiliation: UCL Institute for Liver and Digestive Health, Division of Medicine, University College London & Royal Free London, NHS Foundation Trust, London, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Department of Hepatology, Hôpital Saint Antoine, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chazouillères
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Pares
authors.affiliation: Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway.|Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ståle
authors.initials: S
authors.lastname: Nygård
authors.affiliation: National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Odd H
authors.initials: OH
authors.lastname: Gilja
authors.affiliation: Department of Translational Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wunsch
authors.affiliation: Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy.
authors.forename: Pietro
authors.identifier: 0000-0003-3262-1998
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Carbone
authors.affiliation: Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernuzzi
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Boberg
authors.affiliation: Center for Heart Failure Research, University of Oslo, Oslo, Norway.|Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Røsjø
authors.affiliation: UCL Institute for Liver and Digestive Health, Division of Medicine, University College London & Royal Free London, NHS Foundation Trust, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Rosenberg
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Beuers
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mette
authors.identifier: 0000-0003-2994-2723
authors.initials: M
authors.lastname: Vesterhus
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002170:Canada; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood*; D010641:Phenotype; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood*; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid
keywords: biomarker; enhanced liver fibrosis test; primary sclerosing cholangitis; risk stratification; surrogate endpoint