title: The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis.
abstract: The biochemical response to ursodeoxycholic acid (UDCA)--so-called "treatment response"--strongly predicts long-term outcome in primary biliary cholangitis (PBC). Several long-term prognostic models based solely on the treatment response have been developed that are widely used to risk stratify PBC patients and guide their management. However, they do not take other prognostic variables into account, such as the stage of the liver disease. We sought to improve existing long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We performed Cox's proportional hazards regression analysis of diverse explanatory variables in a derivation cohort of 1,916 UDCA-treated participants. We used nonautomatic backward selection to derive the best-fitting Cox model, from which we derived a multivariable fractional polynomial model. We combined linear predictors and baseline survivor functions in equations to score the risk of a liver transplant or liver-related death occurring within 5, 10, or 15 years. We validated these risk scores in an independent cohort of 1,249 UDCA-treated participants. The best-fitting model consisted of the baseline albumin and platelet count, as well as the bilirubin, transaminases, and alkaline phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and 15-year risk scores were highly accurate (areas under the curve: >0.90).
  
  
  CONCLUSIONS
  The prognosis of PBC patients can be accurately evaluated using the UK-PBC risk scores. They may be used to identify high-risk patients for closer monitoring and second-line therapies, as well as low-risk patients who could potentially be followed up in primary care.
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.|Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Carbone
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sharp
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Flack
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Paximadas
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kelly
authors.initials: K
authors.lastname: Spiess
authors.affiliation: Liver Unit, Royal Victoria Hospital, Belfast, United Kingdom.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Adgey
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Griffiths
authors.affiliation: Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Reyna
authors.initials: R
authors.lastname: Lim
authors.affiliation: Liver Unit, Barts and the London NHS Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Trembling
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Williamson
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Liver Unit, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Aldersley
authors.affiliation: Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bathgate
authors.affiliation: Sheila Sherlock Liver Center, The Royal Free London NHS Foundation Trust, London, United Kingdom.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.affiliation: Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heneghan
authors.affiliation: Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: Neuberger
authors.affiliation: Sheila Sherlock Liver Center, The Royal Free London NHS Foundation Trust, London, United Kingdom.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Center for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.affiliation: Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Alexander
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Sandford
authors.affiliation: Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.|Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: George F
authors.initials: GF
authors.lastname: Mells
mesh_terms: D000465:Algorithms; D002761:Cholangitis / Q000150:complications* / Q000188:drug therapy; D058625:End Stage Liver Disease / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D014580:Ursodeoxycholic Acid