PMID- 30566748
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20230423
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 69
IP  - 5
DP  - 2019 May
TI  - Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis 
      and Development and Validation of a Risk Scoring System.
PG  - 2120-2135
LID - 10.1002/hep.30479 [doi]
AB  - We sought to identify factors that are 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. 
      Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we 
      evaluated clinical variables for their association with 2-year and 10-year 
      outcome through Cox-proportional hazards and C-statistic analyses. We generated 
      risk scores for short-term and long-term outcome prediction, validating their use 
      in two independent cohorts totaling 451 patients. Thirty-six percent of the 
      derivation cohort were transplanted or died over a cumulative follow-up of 7,904 
      years. Serum alkaline phosphatase of at least 2.4 x upper limit of normal at 1 
      year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; 
      C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as 
      was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We 
      developed two risk scoring systems based on age, values of bilirubin, alkaline 
      phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and 
      variceal hemorrhage, which predicted 2-year and 10-year outcomes with good 
      discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk 
      scores were well-validated in our external cohort and outperformed the Mayo 
      Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C 
      statistic = 0.75 and 0.63, respectively). Although heterozygosity for the 
      previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted 
      increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not 
      improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our 
      analyses, based on 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.
CI  - (c) 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of 
      American Association for the Study of Liver Diseases.
FAU - Goode, Elizabeth C
AU  - Goode EC
AUID- ORCID: 0000-0002-8425-1530
AD  - Norfolk and Norwich University Hospital, Norwich, United Kingdom.
AD  - Academic Department of Medical Genetics, Addenbrooke's Hospital, University of 
      Cambridge, Cambridge, United Kingdom.
AD  - Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
AD  - Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
AD  - Cambridge Transplant Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Clark, Allan B
AU  - Clark AB
AD  - Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
FAU - Mells, George F
AU  - Mells GF
AD  - Academic Department of Medical Genetics, Addenbrooke's Hospital, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Srivastava, Brijesh
AU  - Srivastava B
AD  - Academic Department of Medical Genetics, Addenbrooke's Hospital, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Spiess, Kelly
AU  - Spiess K
AD  - Academic Department of Medical Genetics, Addenbrooke's Hospital, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Gelson, William T H
AU  - Gelson WTH
AD  - Cambridge Transplant Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Trivedi, Palak J
AU  - Trivedi PJ
AD  - National Institute for Health Research (NIHR) Birmingham Biomedical Research 
      Centre, Birmingham, United Kingdom.
AD  - Institute of Immunology & Immunotherapy, University of Birmingham, Birmingham, 
      United Kingdom.
AD  - Centre for Rare Diseases, Institute of Translational Medicine, University 
      Hospitals Birmingham, Birmingham, United Kingdom.
FAU - Lynch, Kate D
AU  - Lynch KD
AD  - Translational Gastroenterology Unit, John Radcliffe Hospital, and Nuffield 
      Department of Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Castren, Edit
AU  - Castren E
AD  - Norfolk and Norwich University Hospital, Norwich, United Kingdom.
FAU - Vesterhus, Mette N
AU  - Vesterhus MN
AD  - Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo 
      University Hospital Rikshospitalet, Oslo, Norway.
AD  - Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 
      Norway.
FAU - Karlsen, Tom H
AU  - Karlsen TH
AD  - Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo 
      University Hospital Rikshospitalet, Oslo, Norway.
AD  - Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 
      Norway.
FAU - Ji, Sun-Gou
AU  - Ji SG
AUID- ORCID: 0000-0001-8652-6318
AD  - Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
FAU - Anderson, Carl A
AU  - Anderson CA
AD  - Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
FAU - Thorburn, Douglas
AU  - Thorburn D
AD  - Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom.
FAU - Hudson, Mark
AU  - Hudson M
AD  - Liver Medicine and Transplantation Service, Freeman Hospital, Newcastle, United 
      Kingdom.
FAU - Heneghan, Michael A
AU  - Heneghan MA
AD  - Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
FAU - Aldersley, Mark A
AU  - Aldersley MA
AD  - Department of Hepatology, Leeds Teaching Hospital, Leeds, United Kingdom.
FAU - Bathgate, Andrew
AU  - Bathgate A
AD  - Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United 
      Kingdom.
FAU - Sandford, Richard N
AU  - Sandford RN
AD  - Academic Department of Medical Genetics, Addenbrooke's Hospital, University of 
      Cambridge, Cambridge, United Kingdom.
FAU - Alexander, Graeme J
AU  - Alexander GJ
AD  - Cambridge Transplant Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
AD  - Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom.
FAU - Chapman, Roger W
AU  - Chapman RW
AD  - Translational Gastroenterology Unit, John Radcliffe Hospital, and Nuffield 
      Department of Medicine, University of Oxford, Oxford, United Kingdom.
FAU - Walmsley, Martine
AU  - Walmsley M
AD  - PSC Support, Oxfordshire, United Kingdom.
CN  - UK-PSC Consortium
FAU - Hirschfield, Gideon M
AU  - Hirschfield GM
AD  - National Institute for Health Research (NIHR) Birmingham Biomedical Research 
      Centre, Birmingham, United Kingdom.
AD  - Institute of Immunology & Immunotherapy, University of Birmingham, Birmingham, 
      United Kingdom.
AD  - Centre for Rare Diseases, Institute of Translational Medicine, University 
      Hospitals Birmingham, Birmingham, United Kingdom.
AD  - Toronto Centre for Liver Disease, University Health Network and University of 
      Toronto, Toronto, Canada.
FAU - Rushbrook, Simon M
AU  - Rushbrook SM
AD  - Norfolk and Norwich University Hospital, Norwich, United Kingdom.
AD  - Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
LA  - eng
GR  - Norwegian PSC Research Center/International
GR  - Addenbrooke's Charitable Trust, Cambridge University Hospitals/International
GR  - National Institute of Health Research/International
GR  - Isaac Newton Trust/International
GR  - Health Research/International
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20190304
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA Antigens)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
CIN - Hepatology. 2020 Jan;71(1):398-399. PMID: 31544247
CIN - Hepatology. 2020 Jan;71(1):399-400. PMID: 31550385
CIN - Eur J Gastroenterol Hepatol. 2023 Apr 1;35(4):480-487. PMID: 36719819
MH  - Alkaline Phosphatase/blood
MH  - Cholangitis, Sclerosing/blood/genetics/*mortality/surgery
MH  - Female
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Risk Assessment
MH  - United Kingdom/epidemiology
PMC - PMC6519245
EDAT- 2018/12/20 06:00
MHDA- 2020/06/17 06:00
PMCR- 2019/05/15
CRDT- 2018/12/20 06:00
PHST- 2018/01/20 00:00 [received]
PHST- 2018/12/02 00:00 [accepted]
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2018/12/20 06:00 [entrez]
PHST- 2019/05/15 00:00 [pmc-release]
AID - HEP30479 [pii]
AID - 10.1002/hep.30479 [doi]
PST - ppublish
SO  - Hepatology. 2019 May;69(5):2120-2135. doi: 10.1002/hep.30479. Epub 2019 Mar 4.