The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis

Marco Carbone, Stephen J. Sharp, Steve Flack, Dimitrios Paximadas, Kelly Spiess, Carolyn Adgey, Laura Griffiths, Reyna Lim, Paul Trembling, Kate Williamson, Nick J. Wareham, Mark Aldersley, Andrew Bathgate, Andrew K. Burroughs, Michael A. Heneghan, James M. Neuberger, Douglas Thorburn, Gideon M. Hirschfield, Heather J. Cordell, Graeme J. AlexanderDavid E J Jones, Richard N. Sandford, George F. Mells

Research output: Contribution to journalArticle

Abstract

The biochemical response to ursodeoxycholic acid (UDCA)-so-called "treatment response"-strongly predicts long-term outcome in primary biliary cirrhosis (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.

Original languageEnglish
JournalHepatology
DOIs
Publication statusAccepted/In press - 2015

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End Stage Liver Disease
Biliary Liver Cirrhosis
Ursodeoxycholic Acid
Liver
Physiologic Monitoring
Statistical Models
Transaminases
Platelet Count
Bilirubin
Proportional Hazards Models
Area Under Curve
Alkaline Phosphatase
Survivors
Liver Diseases
Albumins
Primary Health Care
Therapeutics
Regression Analysis
Transplants
Research

ASJC Scopus subject areas

  • Hepatology

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The UK-PBC risk scores : Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis. / Carbone, Marco; Sharp, Stephen J.; Flack, Steve; Paximadas, Dimitrios; Spiess, Kelly; Adgey, Carolyn; Griffiths, Laura; Lim, Reyna; Trembling, Paul; Williamson, Kate; Wareham, Nick J.; Aldersley, Mark; Bathgate, Andrew; Burroughs, Andrew K.; Heneghan, Michael A.; Neuberger, James M.; Thorburn, Douglas; Hirschfield, Gideon M.; Cordell, Heather J.; Alexander, Graeme J.; Jones, David E J; Sandford, Richard N.; Mells, George F.

In: Hepatology, 2015.

Research output: Contribution to journalArticle

Carbone, M, Sharp, SJ, Flack, S, Paximadas, D, Spiess, K, Adgey, C, Griffiths, L, Lim, R, Trembling, P, Williamson, K, Wareham, NJ, Aldersley, M, Bathgate, A, Burroughs, AK, Heneghan, MA, Neuberger, JM, Thorburn, D, Hirschfield, GM, Cordell, HJ, Alexander, GJ, Jones, DEJ, Sandford, RN & Mells, GF 2015, 'The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis', Hepatology. https://doi.org/10.1002/hep.28017
Carbone, Marco ; Sharp, Stephen J. ; Flack, Steve ; Paximadas, Dimitrios ; Spiess, Kelly ; Adgey, Carolyn ; Griffiths, Laura ; Lim, Reyna ; Trembling, Paul ; Williamson, Kate ; Wareham, Nick J. ; Aldersley, Mark ; Bathgate, Andrew ; Burroughs, Andrew K. ; Heneghan, Michael A. ; Neuberger, James M. ; Thorburn, Douglas ; Hirschfield, Gideon M. ; Cordell, Heather J. ; Alexander, Graeme J. ; Jones, David E J ; Sandford, Richard N. ; Mells, George F. / The UK-PBC risk scores : Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis. In: Hepatology. 2015.
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abstract = "The biochemical response to ursodeoxycholic acid (UDCA)-so-called {"}treatment response{"}-strongly predicts long-term outcome in primary biliary cirrhosis (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.",
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T1 - The UK-PBC risk scores

T2 - Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cirrhosis

AU - Carbone, Marco

AU - Sharp, Stephen J.

AU - Flack, Steve

AU - Paximadas, Dimitrios

AU - Spiess, Kelly

AU - Adgey, Carolyn

AU - Griffiths, Laura

AU - Lim, Reyna

AU - Trembling, Paul

AU - Williamson, Kate

AU - Wareham, Nick J.

AU - Aldersley, Mark

AU - Bathgate, Andrew

AU - Burroughs, Andrew K.

AU - Heneghan, Michael A.

AU - Neuberger, James M.

AU - Thorburn, Douglas

AU - Hirschfield, Gideon M.

AU - Cordell, Heather J.

AU - Alexander, Graeme J.

AU - Jones, David E J

AU - Sandford, Richard N.

AU - Mells, George F.

PY - 2015

Y1 - 2015

N2 - The biochemical response to ursodeoxycholic acid (UDCA)-so-called "treatment response"-strongly predicts long-term outcome in primary biliary cirrhosis (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.

AB - The biochemical response to ursodeoxycholic acid (UDCA)-so-called "treatment response"-strongly predicts long-term outcome in primary biliary cirrhosis (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.

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