title: Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis.
abstract: There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We evaluated the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n = 167]; median age 41 years, 74% male) and a validation panel (recruited 2008-2012 [n = 138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, tissue inhibitor of metalloproteinases-1, and propeptide of type III procollagen and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by ELF score tertiles exhibited significantly different transplant-free survival in both panels (P < 0.001), with higher scores associated with shorter survival, which was confirmed in the validation panel stratified by ELF test tertiles (P = 0.003). The ELF test distinguished between mild and severe disease defined by clinical outcome (transplantation or death) with an area under the curve of 0.81 (95% confidence interval [CI] 0.73-0.87) and optimal cutoff of 10.6 (sensitivity 70.2%, specificity 79.1%). In multivariate Cox regression analysis in both panels, ELF score (hazard ratio = 1.9, 95% CI 1.4-2.5, and 1.5, 95% CI 1.1-2.1, respectively) was associated with transplant-free survival independently of the Mayo risk score (hazard ratio = 1.3, 95% CI 1.1-1.6, and 1.6, 95% CI 1.2-2.1, respectively). The ELF test correlated with ultrasound elastography in separate assessments.
  
  
  CONCLUSIONS
  The ELF score is a potent prognostic marker in PSC, independent of the Mayo risk score.
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Vesterhus
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Johannes Roksund
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Holm
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Schrumpf
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.|K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ståle
authors.initials: S
authors.lastname: Nygård
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Godang
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Ina Marie
authors.initials: IM
authors.lastname: Andersen
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Medicine, Division of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Naess
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: UCL Institute for Liver and Digestive Health, Division of Medicine, University College London & Royal Free London, NHS Foundation Trust, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Saffioti
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|The Institute of Clinical Epidemiology and Molecular Biology (EpiGen), Campus Ahus, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Vatn
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 Helge
authors.initials: OH
authors.lastname: Gilja
authors.affiliation: Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Lund-Johansen
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Syversveen
authors.affiliation: Department of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Brabrand
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Parés
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: UCL Institute for Liver and Digestive Health, Division of Medicine, University College London & Royal Free London, NHS Foundation Trust, London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pinzani
authors.affiliation: Department of Medicine, Division of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Medicine, Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Moum
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: K.G. Jebsen Cardiac Research Centre and 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: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Kirsten Muri
authors.initials: KM
authors.lastname: Boberg
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000401:mortality* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D012720:Severity of Illness Index