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Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
Authors :
Marco Carbone Alessandra Nardi Steve Flack Guido Carpino Nikoletta Varvaropoulou Caius Gavrila Ann Spicer Jonathan Badrock Francesca Bernuzzi Vincenzo Cardinale Holly F Ainsworth Michael A Heneghan Douglas Thorburn Andrew Bathgate Rebecca Jones James M Neuberger Pier Maria Battezzati Massimo Zuin Simon Taylor-Robinson Maria F Donato John Kirby Robert Mitchell-Thain Annarosa Floreani Fotios Sampaziotis Luigi Muratori Domenico Alvaro Marco Marzioni Luca Miele Fabio Marra Edoardo Giannini Eugenio Gaudio Vincenzo Ronca Giulia Bonato Laura Cristoferi Federica Malinverno Alessio Gerussi Deborah D Stocken Heather J Cordell Gideon M Hirschfield Graeme J Alexander Richard N Sandford David E Jones Pietro Invernizzi George F Mells Caradog Thomas Meshbah Rahman Tom Yapp Chin Lye Ch'ng Melanie Harrison Richard Sturgess Roman Galaska Chris Healey Jessica Whiteman Marek Czaijkowski Catherine Gray Anton Gunasekera Pranab Gyawli Purushothaman Premchand Steven Mann Keith Elliott Kapil Kapur Alan Watson Graham Foster Paul Trembling Javaid Subhani Rory Harvey Roger McCorry Carolyn Adgey Lucie Hobson Caroline Mulvaney-Jones Richard Evans Thiriloganathan Mathialahan David Ramanaden Jaber Gasem Greta Van Duyvenvoorde Christopher Shorrock Katie Seward Paul Southern Jeremy Tibble Ruth Penn David Gorard Jane Maiden Rose Damant Altaf Palegwala Susan Jones Graeme Alexander George Mells Richard Sandford Sunil Dolwani Martin Prince Valeria Silvestre Matthew Foxton Eleanor Dungca Harriet Mitchison Natalie Wheatley Ian Gooding Helen Doyle Mazn Karmo Melanie Kent Sushma Saksena Delyth Braim Minesh Patel Susan Lord Roland Ede Alison Paton Andrew Austin Nicola Lancaster Joanna Sayer Andrew Gibbins Karen Hogben Chris Hovell Neil Fisher Martyn Carter Konrad Koss Janine Musselwhite Florin Muscariu Andrzej Piotreowicz Alexandra McKay Charles Grimley David Neal Lai Ting Tan Guan Lim Jacqueline Brighton Carole Foale Aftab Ala Athar Saeed Kerry Flahive Gordon Wood Paula Townshend Chris Ford Jonathan Brown Jean Kordula Jane Bowles Mark Wilkinson Caroline Palmer John Ramage Harriet Gordon James Featherstone Jo Ridpath Theodore Ngatchu Sass Levi Syed Shaukat Joy Sadeghian Ray Shidrawi Bronwen Williams George Abouda Sarah Jones Claire Duggan Abigail Hynes Mark Narain Ian Rees Imroz Salam Mary Crossey Ashley Brown Carolyn MacNicol Simon Williams Elva Wilhelmsen Paul Banim Parizade Raymode Andrew Chilton Debasish Das Hye-Jeong Lee Howard Curtis Michael Heneghan Markus Gess Emma Durant IM Drake Rebecca Bishop Mervyn Davies Mark Aldersley Noma Ncube Alistair McNair Raj Srirajaskanthan Sambit Sen Rebecca Casey George Bird Mike Mendall Caroline Cowley Adrian Barnardo Paul Kitchen Kevin Yoong Kelly Amore Dawn Sirdefield Jacky Orpe Ray Mathew George MacFaul Aruna Wrigth Amir Shah Chris Evans Janie Keggans Bridget Bird Gwen Baxter Subrata Saha Katharine Pollock Maggie Hughes Peter Bramley Emma Grieve Karin Young Andrew Fraser Ashis Mukhopadhya Kate Ocker Peter Mills Francis Hines Chris Shallcross Joy Wilkins Leonie Grellier Stewart Campbell Kirsty Martin Caron Innes Alan Shepherd Simon Rushbrook Talal Valliani Robert Przemioslo Helen Fairlamb Chris Macdonald Anne Eastick Jane Metcalf Elizabeth Tanqueray Udi Shmueli Becky Holbrook Andrew Davis Julie Browning Asifabbas Naqvi Kirsten Walker Tom Lee Juliette Verheyden Susan Slininger Stephen D Ryder Roger Chapman Jane Collier Denise O'Donnell Lizzie Stafford Kate Williamson Linda Kent Howard Klass Mary Ninkovic Linda March Matthew Cramp Diane Simpson Christine Dickson Nicholas Sharer Maria Hayes Patrick Goggin Mary Quinne Sallyanne Pearson Barbara Hoeroldt Linda Jones Alice Wright Jonathan Booth Alison Loftus George Lipscomb Hannah Dewhurst Emma Gunter Earl Williams Anna Fouracres Liz Farrington Lyn Graves Hyder Hussaini Bill Stableforth Suzie Marriott Reuben Ayres Marina Leoni Andrew Burroughs Eileen Marshall David Tyrer Kate Martin Martin Lombard Imran Patanwala Lola Dali-Kemmery Victoria Lambourne Julia Maltby Samir Vyas Julie Colley Bal Shinder Saket Singhal Jayne Jones Marisa Mills Dermot Gleeson Mandy Carnahan Jeff Butterworth Kerenza Boulton Natalie Taylor Keith George Tim Harding Julie Tregonning Andrew Douglass Carly Brown Gayle Clifford Simon Panter Denise Gocher Jeremy Shearman Gary Bray Maria Hamilton Graham Butcher Daniel Forton John Mclindon Janette Curtis Debashis Das Tracey Shewan Matthew Cowan Gregory Whatley Mariam Nasseri Bob Grover Nurani Sivaramakrishnan Samantha Ducker Kathryn Houghton David Jones Laura Griffiths Sherill Tripoli Maxton Pitcher Ervin Shpuza Nikki White Deb Ghosh Andrew Douds Marie Green Matthew Brookes Lourdes Cumlat Voi Shim Wong Karen Warner Kimberley Netherton Adtya Mandal Snjiv Jain Hemant Gupta Pradeep Sanghi Steve Pereira James Neuberger Bridget Gunson Gideon Hirschfield Reina Teegan Lim Susan Gallagher Darren Clement Alison Brind Gill Watts Mcdonald Mupudzi Mark Wright Jane Gitahi Fiona Gordon Denis Gocher Esther Unitt Hilary Pateman Sally Batham Toby Delahooke Allister Grant Jill Conder Andrew Higham Mark Cox Lynn O'Donohoe Lynn Currie Alistair King Metod Oblak Carole Collins Simon Whalley Marie Quinn Yolanda Baird Isobel Amey Jocelyn Fraser Andy Li Donna Cotterill Andrew Bell Amit Singhal Ian Gee Sandra Greer Yeng Ang Rupert Ransford Joanna Allison James Gotto Simon Dyer Helen Sweeting Charles Millson Giancarlo Labbadia Maria Consiglia Bragazzi Pietro Andreone Francesco Azzaroli Andrea Galli Mirko Tarocchi Antonio Gasbarrini Antonio Grieco Giuseppe Marrone Maria Francesca Donato Luca Valenti Luca Maroni Cristina Rigamonti Antonino Picciotto Carbone, M Nardi, A Flack, S Carpino, G Varvaropoulou, N Gavrila, C Spicer, A Badrock, J Bernuzzi, F Cardinale, V Ainsworth, H Heneghan, M Thorburn, D Bathgate, A Jones, R Neuberger, J Battezzati, P Zuin, M Taylor-Robinson, S Donato, M Kirby, J Mitchell-Thain, R Floreani, A Sampaziotis, F Muratori, L Alvaro, D Marzioni, M Miele, L Marra, F Giannini, E Gaudio, E Ronca, V Bonato, G Cristoferi, L Malinverno, F Gerussi, A Stocken, D Cordell, H Hirschfield, G Alexander, G Sandford, R Jones, D Invernizzi, P Mells, G Thomas, C Rahman, M Yapp, T Lye Ch'ng, C Harrison, M Sturgess, R Galaska, R Healey, C Whiteman, J Czaijkowski, M Gray, C Gunasekera, A Gyawli, P Premchand, P Mann, S Elliott, K Kapur, K Watson, A Foster, G Trembling, P Subhani, J Harvey, R Mccorry, R Adgey, C Hobson, L Mulvaney-Jones, C Evans, R Mathialahan, T Ramanaden, D Gasem, J Van Duyvenvoorde, G Shorrock, C Seward, K Southern, P Tibble, J Penn, R Gorard, D Maiden, J Damant, R Palegwala, A Jones, S Dolwani, S Prince, M Silvestre, V Foxton, M Dungca, E Mitchison, H Wheatley, N Gooding, I Doyle, H Karmo, M Kent, M Saksena, S Braim, D Patel, M Lord, S Ede, R Paton, A Austin, A Lancaster, N Sayer, J Gibbins, A Hogben, K Hovell, C Fisher, N Carter, M Koss, K Musselwhite, J Muscariu, F Piotreowicz, A Mckay, A Grimley, C Neal, D Ting Tan, L Lim, G Brighton, J Foale, C Ala, A Saeed, A Flahive, K Wood, G Townshend, P Ford, C Brown, J Kordula, J Bowles, J Wilkinson, M Palmer, C Ramage, J Gordon, H Featherstone, J Ridpath, J Ngatchu, T Levi, S Shaukat, S Sadeghian, J Shidrawi, R Williams, B Abouda, G Duggan, C Hynes, A Narain, M Rees, I Salam, I Crossey, M Brown, A Macnicol, C Williams, S Wilhelmsen, E Banim, P Raymode, P Chilton, A Das, D Lee, H Curtis, H Gess, M Durant, E Drake, I Bishop, R Davies, M Aldersley, M Ncube, N Mcnair, A Srirajaskanthan, R Sen, S Casey, R Bird, G Mendall, M Cowley, C Barnardo, A Kitchen, P Yoong, K Amore, K Sirdefield, D Orpe, J Mathew, R Macfaul, G Wrigth, A Shah, A Evans, C Keggans, J Bird, B Baxter, G Saha, S Pollock, K Hughes, M Bramley, P Grieve, E Young, K Fraser, A Mukhopadhya, A Ocker, K Mills, P Hines, F Shallcross, C Wilkins, J Grellier, L Campbell, S Martin, K Innes, C Shepherd, A Rushbrook, S Valliani, T Przemioslo, R Fairlamb, H Macdonald, C Eastick, A Metcalf, J Tanqueray, E Shmueli, U Holbrook, B Davis, A Browning, J Naqvi, A Walker, K Lee, T Verheyden, J Slininger, S Ryder, S Chapman, R Collier, J O'Donnell, D Stafford, L Williamson, K Kent, L Klass, H Ninkovic, M March, L Cramp, M Simpson, D Dickson, C Sharer, N Hayes, M Goggin, P Quinne, M Pearson, S Hoeroldt, B Jones, L Wright, A Booth, J Loftus, A Lipscomb, G Dewhurst, H Gunter, E Williams, E Fouracres, A Farrington, L Graves, L Hussaini, H Stableforth, B Marriott, S Ayres, R Leoni, M Burroughs, A Marshall, E Tyrer, D Lombard, M Patanwala, I Dali-Kemmery, L Lambourne, V Maltby, J Vyas, S Colley, J Shinder, B Singhal, S Jones, J Mills, M Gleeson, D Carnahan, M Butterworth, J Boulton, K Taylor, N George, K Harding, T Tregonning, J Douglass, A Brown, C Clifford, G Panter, S Gocher, D Shearman, J Bray, G Hamilton, M Butcher, G Forton, D Mclindon, J Curtis, J Shewan, T Cowan, M Whatley, G Nasseri, M Grover, B Sivaramakrishnan, N Ducker, S Houghton, K Griffiths, L Tripoli, S Pitcher, M Shpuza, E White, N Ghosh, D Douds, A Green, M Brookes, M Cumlat, L Wong, V Warner, K Netherton, K Mandal, A Jain, S Gupta, H Sanghi, P Pereira, S Gunson, B Lim, R Gallagher, S Clement, D Brind, A Watts, G Mupudzi, M Wright, M Gitahi, J Gordon, F Unitt, E Pateman, H Batham, S Delahooke, T Grant, A Conder, J Higham, A Cox, M O'Donohoe, L Currie, L King, A Oblak, M Collins, C Whalley, S Quinn, M Baird, Y Amey, I Fraser, J Li, A Cotterill, D Bell, A Singhal, A Gee, I Greer, S Ang, Y Ransford, R Allison, J Gotto, J Dyer, S Sweeting, H Millson, C Labbadia, G Bragazzi, M Andreone, P Azzaroli, F Galli, A Tarocchi, M Gasbarrini, A Grieco, A Marrone, G Valenti, L Maroni, L Rigamonti, C Picciotto, A Sampaziotis, Fotios [0000-0003-0812-7586] Sandford, Richard [0000-0002-7437-0560] Apollo - University of Cambridge Repository Carbone, Marco Nardi, Alessandra Flack, Steve Carpino, Guido Varvaropoulou, Nikoletta Gavrila, Caiu Spicer, Ann Badrock, Jonathan Bernuzzi, Francesca Cardinale, Vincenzo Ainsworth, Holly F Heneghan, Michael A Thorburn, Dougla Bathgate, Andrew Jones, Rebecca Neuberger, James M Battezzati, Pier Maria Zuin, Massimo Taylor-Robinson, Simon Donato, Maria F Kirby, John Mitchell-Thain, Robert Floreani, Annarosa Sampaziotis, Fotio Muratori, Luigi Alvaro, Domenico Marzioni, Marco Miele, Luca Marra, Fabio Giannini, Edoardo Gaudio, Eugenio Ronca, Vincenzo Bonato, Giulia Cristoferi, Laura Malinverno, Federica Gerussi, Alessio Stocken, Deborah D Cordell, Heather J Hirschfield, Gideon M Alexander, Graeme J Sandford, Richard N Jones, David E Invernizzi, Pietro Mells, George F Thomas, Caradog Rahman, Meshbah Yapp, Tom Lye Ch'ng, Chin Harrison, Melanie Sturgess, Richard Galaska, Roman Healey, Chri Whiteman, Jessica Czaijkowski, Marek Gray, Catherine Gunasekera, Anton Gyawli, Pranab Premchand, Purushothaman Mann, Steven Elliott, Keith Kapur, Kapil Watson, Alan Foster, Graham Trembling, Paul Subhani, Javaid Harvey, Rory McCorry, Roger Adgey, Carolyn Hobson, Lucie Mulvaney-Jones, Caroline Evans, Richard Mathialahan, Thiriloganathan Ramanaden, David Gasem, Jaber Van Duyvenvoorde, Greta Shorrock, Christopher Seward, Katie Southern, Paul Tibble, Jeremy Penn, Ruth Gorard, David Maiden, Jane Damant, Rose Palegwala, Altaf Jones, Susan Alexander, Graeme Mells, George Sandford, Richard Dolwani, Sunil Prince, Martin Silvestre, Valeria Foxton, Matthew Dungca, Eleanor Mitchison, Harriet Wheatley, Natalie Gooding, Ian Doyle, Helen Karmo, Mazn Kent, Melanie Saksena, Sushma Braim, Delyth Patel, Minesh Lord, Susan Ede, Roland Paton, Alison Austin, Andrew Lancaster, Nicola Sayer, Joanna Gibbins, Andrew Hogben, Karen Hovell, Chri Fisher, Neil Carter, Martyn Koss, Konrad Musselwhite, Janine Muscariu, Florin Piotreowicz, Andrzej McKay, Alexandra Grimley, Charle Neal, David Ting Tan, Lai Lim, Guan Brighton, Jacqueline Foale, Carole Ala, Aftab Saeed, Athar Flahive, Kerry Wood, Gordon Townshend, Paula Ford, Chri Brown, Jonathan Kordula, Jean Bowles, Jane Wilkinson, Mark Palmer, Caroline Ramage, John Gordon, Harriet Featherstone, Jame Ridpath, Jo Ngatchu, Theodore Levi, Sa Shaukat, Syed Sadeghian, Joy Shidrawi, Ray Williams, Bronwen Abouda, George Jones, Sarah Duggan, Claire Hynes, Abigail Narain, Mark Rees, Ian Salam, Imroz Crossey, Mary Brown, Ashley MacNicol, Carolyn Williams, Simon Wilhelmsen, Elva Banim, Paul Raymode, Parizade Chilton, Andrew Das, Debasish Lee, Hye-Jeong Curtis, Howard Heneghan, Michael Gess, Marku Durant, Emma Drake, I.M. Bishop, Rebecca Davies, Mervyn Aldersley, Mark Ncube, Noma McNair, Alistair Srirajaskanthan, Raj Sen, Sambit Casey, Rebecca Bird, George Mendall, Mike Cowley, Caroline Barnardo, Adrian Kitchen, Paul Yoong, Kevin Amore, Kelly Sirdefield, Dawn Orpe, Jacky Mathew, Ray MacFaul, George Wrigth, Aruna Shah, Amir Evans, Chri Keggans, Janie Bird, Bridget Baxter, Gwen Saha, Subrata Pollock, Katharine Hughes, Maggie Bramley, Peter Grieve, Emma Young, Karin Fraser, Andrew Mukhopadhya, Ashi Ocker, Kate Mills, Peter Hines, Franci Shallcross, Chri Wilkins, Joy Grellier, Leonie Campbell, Stewart Martin, Kirsty Innes, Caron Shepherd, Alan Rushbrook, Simon Valliani, Talal Przemioslo, Robert Fairlamb, Helen Macdonald, Chri Eastick, Anne Metcalf, Jane Tanqueray, Elizabeth Shmueli, Udi Holbrook, Becky Davis, Andrew Browning, Julie Naqvi, Asifabba Walker, Kirsten Lee, Tom Verheyden, Juliette Slininger, Susan Ryder, Stephen D Chapman, Roger Collier, Jane O'Donnell, Denise Stafford, Lizzie Williamson, Kate Kent, Linda Klass, Howard Ninkovic, Mary March, Linda Cramp, Matthew Simpson, Diane Dickson, Christine Sharer, Nichola Hayes, Maria Goggin, Patrick Quinne, Mary Pearson, Sallyanne Hoeroldt, Barbara Jones, Linda Wright, Alice Booth, Jonathan Loftus, Alison Lipscomb, George Dewhurst, Hannah Gunter, Emma Williams, Earl Fouracres, Anna Farrington, Liz Graves, Lyn Hussaini, Hyder Stableforth, Bill Marriott, Suzie Ayres, Reuben Leoni, Marina Burroughs, Andrew Marshall, Eileen Tyrer, David Martin, Kate Lombard, Martin Patanwala, Imran Dali-Kemmery, Lola Lambourne, Victoria Maltby, Julia Vyas, Samir Colley, Julie Shinder, Bal Singhal, Saket Jones, Jayne Mills, Marisa Gleeson, Dermot Carnahan, Mandy Butterworth, Jeff Boulton, Kerenza Taylor, Natalie George, Keith Harding, Tim Tregonning, Julie Douglass, Andrew Brown, Carly Clifford, Gayle Panter, Simon Gocher, Denise Shearman, Jeremy Bray, Gary Hamilton, Maria Butcher, Graham Forton, Daniel Mclindon, John Curtis, Janette Das, Debashi Shewan, Tracey Cowan, Matthew Whatley, Gregory Nasseri, Mariam Grover, Bob Sivaramakrishnan, Nurani Ducker, Samantha Houghton, Kathryn Jones, David Griffiths, Laura Tripoli, Sherill Pitcher, Maxton Shpuza, Ervin White, Nikki Ghosh, Deb Douds, Andrew Green, Marie Brookes, Matthew Cumlat, Lourde Wong, Voi Shim Warner, Karen Netherton, Kimberley Mandal, Adtya Jain, Snjiv Gupta, Hemant Sanghi, Pradeep Pereira, Steve Neuberger, Jame Gunson, Bridget Hirschfield, Gideon Lim, Reina Teegan Gallagher, Susan Clement, Darren Brind, Alison Watts, Gill Mupudzi, Mcdonald Wright, Mark Gitahi, Jane Gordon, Fiona Gocher, Deni Unitt, Esther Pateman, Hilary Batham, Sally Delahooke, Toby Grant, Allister Conder, Jill Higham, Andrew Cox, Mark O'Donohoe, Lynn Currie, Lynn King, Alistair Oblak, Metod Collins, Carole Whalley, Simon Quinn, Marie Baird, Yolanda Amey, Isobel Fraser, Jocelyn Li, Andy Cotterill, Donna Bell, Andrew Singhal, Amit Gee, Ian Greer, Sandra Ang, Yeng Ransford, Rupert Allison, Joanna Gotto, Jame Dyer, Simon Sweeting, Helen Millson, Charle Labbadia, Giancarlo Bragazzi, Maria Consiglia Andreone, Pietro Azzaroli, Francesco Galli, Andrea Tarocchi, Mirko Gasbarrini, Antonio Grieco, Antonio Marrone, Giuseppe Donato, Maria Francesca Valenti, Luca Maroni, Luca Rigamonti, Cristina Picciotto, Antonino Medical Research Council (MRC)
Source :
Italian PBC Study Group and the UK–PBC Consortium 2018, ' Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis : development and validation of the UDCA Response Score ', The Lancet Gastroenterology and Hepatology, vol. 3, no. 9, pp. 626-634 . https://doi.org/10.1016/S2468-1253(18)30163-8
Publication Year :
2018
Publisher :
Elsevier Ltd, 2018.
Abstract
Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p
Details
Language :
English
Database :
OpenAIRE
Journal :
Italian PBC Study Group and the UK–PBC Consortium 2018, ' Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis : development and validation of the UDCA Response Score ', The Lancet Gastroenterology and Hepatology, vol. 3, no. 9, pp. 626-634 . https://doi.org/10.1016/S2468-1253(18)30163-8
Accession number :
edsair.doi.dedup.....fd34d9f83cc5ab25a64bb515bee292a5