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Hepatology. 2018 Dec 19. doi: 10.1002/hep.30479. [Epub ahead of print]

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.

Author information

1
Norfolk and Norwich University Hospital, Norwich, UK.
2
Academic Department of Medical Genetics, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
3
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
4
Norwich Medical School, University of East Anglia, Norwich, UK.
5
Cambridge Transplant Centre, Addenbrooke's Hospital, Cambridge, UK.
6
National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre.
7
Institute of Immunology & Immunotherapy, University of Birmingham, UK.
8
Centre for Rare Diseases, Institute of Translational Medicine, University Hospitals Birmingham.
9
Translational Gastroenterology Unit, John Radcliffe Hospital, Nuffield Department of Medicine, University of Oxford, UK.
10
Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
11
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
12
Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
13
Liver Medicine and Transplantation Service, Freeman Hospital, Newcastle, UK.
14
Institute of Liver Studies, Kings College Hospital, London, UK.
15
Department of Hepatology, Leeds Teaching Hospital, Leeds, UK.
16
Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
17
PSC Support, Oxfordshire, UK.
18
Toronto Centre for Liver Disease, University Health Network and University of Toronto, Toronto, Canada.

Abstract

BACKGROUND & AIMS:

We sought to identify factors predictive of liver transplantation or death in patients with Primary Sclerosing Cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting.

METHODS:

Analysing data from 1001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2- and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short- and long-term outcome prediction, validating their use in two independent cohorts totalling 451 patients.

RESULTS:

36% of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase ≥2.4×ULN at 1 year post diagnosis, was predictive of 10-year outcome (HR=3.05, C=0.63, median transplant-free survival 63 versus 108 months, p<0.0001), as was the presence of extra-hepatic biliary disease (HR=1.45, p=0.01). We developed two risk scoring systems based upon age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extra-hepatic biliary disease and variceal haemorrhage, which predicted 2- and 10-year outcome with good discrimination (C=0.81 and 0.80 respectively). Both UK-PSC risk scores were well-validated in our external cohort, and out-performed the Mayo and APRI scores (C=0.75 and 0.63 respectively). Whilst heterozygosity for the previously validated HLA-DR*03:01 risk allele predicted increased risk of adverse outcome (HR=1.33, p=.001), its addition did not improve the predictive accuracy the UK-PSC risk scores.

CONCLUSIONS:

Our analyses, based upon a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation. This article is protected by copyright. All rights reserved.

KEYWORDS:

UK-PSC; autoimmune liver disease; cholestasis; prognostic factor, risk score

PMID:
30566748
DOI:
10.1002/hep.30479

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