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.
| Original language | English |
|---|---|
| Pages (from-to) | 930-950 |
| Number of pages | 21 |
| Journal | Hepatology |
| Volume | 63 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2016 |
| Externally published | Yes |
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In: Hepatology, Vol. 63, No. 3, 01.03.2016, p. 930-950.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
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 cholangitis
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.
AU - Jones, David
AU - Kirby, John
AU - Alexander, Graeme
AU - Sandford, Richard
AU - Taylor-Robinson, Simon
AU - Ch'ng, Chin Lye
AU - Rahman, Mesbah
AU - Yapp, Tom
AU - Sturgess, Richard
AU - Healey, Christopher
AU - Czajkowski, Marek
AU - Gunasekera, Anton
AU - Gyawali, Pranab
AU - Premchand, Purushothaman
AU - Kapur, Kapil
AU - Marley, Richard
AU - Foster, Graham
AU - Watson, Alan
AU - Dias, Aruna
AU - Subhani, Javaid
AU - Harvey, Rory
AU - McCorry, Roger
AU - Ramanaden, David
AU - Gasem, Jaber
AU - Evans, Richard
AU - Mathialahan, Thiriloganathan
AU - Shorrock, Christopher
AU - Lipscomb, George
AU - Southern, Paul
AU - Tibble, Jeremy
AU - Gorard, David
AU - Palegwala, Altaf
AU - Jones, Susan
AU - Dawwas, Mohamed
AU - Dolwani, Sunil
AU - Prince, Martin
AU - Foxton, Matthew
AU - Elphick, David
AU - Mitchison, Harriet
AU - Gooding, Ian
AU - Karmo, Mazn
AU - Saksena, Sushma
AU - Mendall, Mike
AU - Patel, Minesh
AU - Ede, Roland
AU - Austin, Andrew
AU - Sayer, Joanna
AU - Hankey, Lorraine
AU - Hovell, Christopher
AU - Fisher, Neil
AU - Carter, Martyn
AU - Koss, Konrad
AU - Piotrowicz, Andrzej
AU - Grimley, Charles
AU - Neal, David
AU - Lim, Guan
AU - Levi, Sass
AU - Ala, Aftab
AU - Broad, Andrea
AU - Saeed, Athar
AU - Wood, Gordon
AU - Brown, Jonathan
AU - Wilkinson, Mark
AU - Gordon, Harriet
AU - Ramage, John
AU - Ridpath, Jo
AU - Ngatchu, Theodore
AU - Grover, Bob
AU - Shaukat, Syed
AU - Shidrawi, Ray
AU - Abouda, George
AU - Ali, Faiz
AU - Rees, Ian
AU - Salam, Imroz
AU - Narain, Mark
AU - Brown, Ashley
AU - Williams, Simon
AU - Grellier, Leonie
AU - Banim, Paul
AU - Chilton, Andrew
AU - Curtis, Howard
AU - Gess, Markus
AU - Drake, Ian
AU - Davies, Mervyn
AU - Jones, Rebecca
AU - McNair, Alastair
AU - Srirajaskanthan, Raj
AU - Pitcher, Maxton
AU - Sen, Sambit
AU - Bird, George
AU - Barnardo, Adrian
AU - Kitchen, Paul
AU - Yoong, Kevin
AU - Chirag, Oza
AU - Sivaramakrishnan, Nurani
AU - MacFaul, George
AU - Shah, Amir
AU - Evans, Chris
AU - Saha, Subrata
AU - Pollock, Katharine
AU - Bramley, Peter
AU - Mukhopadhya, Ashis
AU - Fraser, Andrew
AU - Mills, Peter
AU - Shallcross, Christopher
AU - Campbell, Stewart
AU - Shepherd, Alan
AU - Dillon, John
AU - Rushbrook, Simon
AU - Przemioslo, Robert
AU - Macdonald, Christopher
AU - Metcalf, Jane
AU - Shmueli, Udi
AU - Davis, Andrew
AU - Naqvi, Asifabbas
AU - Lee, Tom
AU - Ryder, Stephen D.
AU - Collier, Jane
AU - Klass, Howard
AU - Ninkovic, Mary
AU - Cramp, Matthew
AU - Sharer, Nicholas
AU - Aspinall, Richard
AU - Goggin, Patrick
AU - Ghosh, Deb
AU - Douds, Andrew
AU - Hoeroldt, Barbara
AU - Booth, Jonathan
AU - Williams, Earl
AU - Hussaini, Hyder
AU - Stableforth, William
AU - Ayres, Reuben
AU - Marshall, Eileen
AU - Mann, Steven
AU - Lombard, Martin
AU - Richardson, Paul
AU - Patanwala, Imran
AU - Maltby, Julia
AU - Brookes, Matthew
AU - Mathew, Ray
AU - Vyas, Samir
AU - Singhal, Saket
AU - Gleeson, Dermot
AU - Misra, Sharat
AU - Butterworth, Jeff
AU - George, Keith
AU - Harding, Tim
AU - Douglass, Andrew
AU - Panter, Simon
AU - Shearman, Jeremy
AU - Bray, Gary
AU - Butcher, Graham
AU - Forton, Daniel
AU - Mclindon, John
AU - Das, Debashis
AU - Cowan, Matthew
AU - Whatley, Gregory
AU - Mandal, Aditya
AU - Gupta, Hemant
AU - Sanghi, Pradeep
AU - Jain, Sanjiv
AU - Pereira, Steve
AU - Prasad, Geeta
AU - Watts, Gill
AU - Wright, Mark
AU - Gordon, Fiona
AU - Unitt, Esther
AU - Grant, Allister
AU - Delahooke, Toby
AU - Higham, Andrew
AU - Brind, Alison
AU - Cox, Mark
AU - Ramakrishnan, Subramaniam
AU - King, Alistair
AU - Collins, Carole
AU - Whalley, Simon
AU - Li, Andy
AU - Fraser, Jocelyn
AU - Bell, Andrew
AU - Wong, Voi Shim
AU - Singhal, Amit
AU - Gee, Ian
AU - Ang, Yeng
AU - Ransford, Rupert
AU - Gotto, James
AU - Millson, Charles
AU - Bowles, Jane
AU - Thomas, Caradog
AU - Harrison, Melanie
AU - Galaska, Roman
AU - Kendall, Jennie
AU - Whiteman, Jessica
AU - Lawlor, Caroline
AU - Gray, Catherine
AU - Elliott, Keith
AU - Mulvaney-Jones, Caroline
AU - Hobson, Lucie
AU - Van Duyvenvoorde, Greta
AU - Loftus, Alison
AU - Seward, Katie
AU - Penn, Ruth
AU - Maiden, Jane
AU - Damant, Rose
AU - Hails, Janeane
AU - Cloudsdale, Rebecca
AU - Silvestre, Valeria
AU - Glenn, Sue
AU - Dungca, Eleanor
AU - Wheatley, Natalie
AU - Doyle, Helen
AU - Kent, Melanie
AU - Hamilton, Caroline
AU - Braim, Delyth
AU - Wooldridge, Helen
AU - Abrahams, Rachel
AU - Paton, Alison
AU - Lancaster, Nicola
AU - Gibbins, Andrew
AU - Hogben, Karen
AU - Desousa, Phillipa
AU - Muscariu, Florin
AU - Musselwhite, Janine
AU - McKay, Alexandra
AU - Tan, Lai Ting
AU - Foale, Carole
AU - Brighton, Jacqueline
AU - Flahive, Kerry
AU - Nambela, Estelle
AU - Townshend, Paula
AU - Ford, Chris
AU - Holder, Sophie
AU - Palmer, Caroline
AU - Featherstone, James
AU - Nasseri, Mariam
AU - Sadeghian, Joy
AU - Williams, Bronwen
AU - Thomas, Carol
AU - Rolls, Sally Ann
AU - Hynes, Abigail
AU - Duggan, Claire
AU - Jones, Sarah
AU - Crossey, Mary
AU - Stansfield, Glynis
AU - MacNicol, Carolyn
AU - Wilkins, Joy
AU - Wilhelmsen, Elva
AU - Raymode, Parizade
AU - Lee, Hye Jeong
AU - Durant, Emma
AU - Bishop, Rebecca
AU - Ncube, Noma
AU - Tripoli, Sherill
AU - Casey, Rebecca
AU - Cowley, Caroline
AU - Miller, Richard
AU - Houghton, Kathryn
AU - Ducker, Samantha
AU - Wright, Fiona
AU - Bird, Bridget
AU - Baxter, Gwen
AU - Keggans, Janie
AU - Hughes, Maggie
AU - Grieve, Emma
AU - Young, Karin
AU - D. Williams, Williams
AU - Ocker, Kate
AU - Hines, Frances
AU - Martin, Kirsty
AU - Innes, Caron
AU - Valliani, Talal
AU - Fairlamb, Helen
AU - Thornthwaite, Sarah
AU - Eastick, Anne
AU - Tanqueray, Elizabeth
AU - Morrison, Jennifer
AU - Holbrook, Becky
AU - Browning, Julie
AU - Walker, Kirsten
AU - Congreave, Susan
AU - Verheyden, Juliette
AU - Slininger, Susan
AU - Stafford, Lizzie
AU - Denise O'Donnell, O'Donnell
AU - Ainsworth, Mark
AU - Lord, Susan
AU - Kent, Linda
AU - March, Linda
AU - Dickson, Christine
AU - Simpson, Diane
AU - Longhurst, Beverley
AU - Hayes, Maria
AU - Shpuza, Ervin
AU - White, Nikki
AU - Besley, Sarah
AU - Pearson, Sallyanne
AU - Wright, Alice
AU - Jones, Linda
AU - Gunter, Emma
AU - Dewhurst, Hannah
AU - Fouracres, Anna
AU - Farrington, Liz
AU - Graves, Lyn
AU - Marriott, Suzie
AU - Leoni, Marina
AU - Tyrer, David
AU - Martin, Kate
AU - Dali-kemmery, Lola
AU - Lambourne, Victoria
AU - Green, Marie
AU - Sirdefield, Dawn
AU - Amor, Kelly
AU - Colley, Julie
AU - Shinder, Bal
AU - Jones, Jayne
AU - Mills, Marisa
AU - Carnahan, Mandy
AU - Taylor, Natalie
AU - Boulton, Kerenza
AU - Tregonning, Julie
AU - Brown, Carly
AU - Clifford, Gayle
AU - Archer, Emily
AU - Hamilton, Maria
AU - Curtis, Janette
AU - Shewan, Tracey
AU - Walsh, Sue
AU - Warner, Karen
AU - Netherton, Kimberley
AU - Mupudzi, Mcdonald
AU - Gunson, Bridget
AU - Gitahi, Jane
AU - Gocher, Denise
AU - Batham, Sally
AU - Pateman, Hilary
AU - Desmennu, Senayon
AU - Conder, Jill
AU - Clement, Darren
AU - Gallagher, Susan
AU - Orpe, Jacky
AU - Chan, Pui Ching
AU - Currie, Lynn
AU - Lynn O'Donohoe, O'Donohoe
AU - Oblak, Metod
AU - Morgan, Lisa
AU - Quinn, Marie
AU - Amey, Isobel
AU - Baird, Yolanda
AU - Cotterill, Donna
AU - Cumlat, Lourdes
AU - Winter, Louise
AU - Greer, Sandra
AU - Spurdle, Katie
AU - Allison, Joanna
AU - Dyer, Simon
AU - Sweeting, Helen
AU - Kordul, Jean
N1 - Publisher Copyright: © 2016 by the American Association for the Study of Liver Diseases.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84949105616&partnerID=8YFLogxK
U2 - 10.1002/hep.28017
DO - 10.1002/hep.28017
M3 - Artículo
C2 - 26223498
AN - SCOPUS:84949105616
SN - 0270-9139
VL - 63
SP - 930
EP - 950
JO - Hepatology
JF - Hepatology
IS - 3
ER -