Abstract
| Lingua originale | Inglese |
|---|---|
| pagine (da-a) | 626-634 |
| Numero di pagine | 9 |
| Rivista | The Lancet Gastroenterology and Hepatology |
| Volume | 3 |
| Numero di pubblicazione | 9 |
| DOI | |
| Stato di pubblicazione | Pubblicato - 2018 |
All Science Journal Classification (ASJC) codes
- Epatologia
- Gastroenterologia
Keywords
- Gastroenterology
- Hepatology
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In: The Lancet Gastroenterology and Hepatology, Vol. 3, N. 9, 2018, pag. 626-634.
Risultato della ricerca: Contributo in rivista › Articolo
TY - JOUR
T1 - Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
AU - Carbone, Marco
AU - Nardi, Alessandra
AU - Flack, Steve
AU - Carpino, Guido
AU - Varvaropoulou, Nikoletta
AU - Gavrila, Caius
AU - Spicer, Ann
AU - Badrock, Jonathan
AU - Bernuzzi, Francesca
AU - Cardinale, Vincenzo
AU - Ainsworth, Holly F
AU - Heneghan, Michael A
AU - Thorburn, Douglas
AU - Bathgate, Andrew
AU - Jones, Rebecca
AU - Neuberger, James M
AU - Battezzati, Pier Maria
AU - Zuin, Massimo
AU - Taylor-Robinson, Simon
AU - Donato, Maria F
AU - Kirby, John
AU - Mitchell-Thain, Robert
AU - Floreani, Annarosa
AU - Sampaziotis, Fotios
AU - Muratori, Luigi
AU - Alvaro, Domenico
AU - Marzioni, Marco
AU - Miele, Luca
AU - Marra, Fabio
AU - Giannini, Edoardo
AU - Gaudio, Eugenio
AU - Ronca, Vincenzo
AU - Bonato, Giulia
AU - Cristoferi, Laura
AU - Malinverno, Federica
AU - Gerussi, Alessio
AU - Stocken, Deborah D
AU - Cordell, Heather J
AU - Hirschfield, Gideon M
AU - Alexander, Graeme J
AU - Sandford, Richard N
AU - Jones, David E
AU - Invernizzi, Pietro
AU - Mells, George F
AU - Thomas, Caradog
AU - Rahman, Meshbah
AU - Yapp, Tom
AU - Lye Ch'ng, Chin
AU - Harrison, Melanie
AU - Sturgess, Richard
AU - Galaska, Roman
AU - Healey, Chris
AU - Whiteman, Jessica
AU - Czaijkowski, Marek
AU - Gray, Catherine
AU - Gunasekera, Anton
AU - Gyawli, Pranab
AU - Premchand, Purushothaman
AU - Mann, Steven
AU - Elliott, Keith
AU - Kapur, Kapil
AU - Watson, Alan
AU - Foster, Graham
AU - Trembling, Paul
AU - Subhani, Javaid
AU - Harvey, Rory
AU - McCorry, Roger
AU - Adgey, Carolyn
AU - Hobson, Lucie
AU - Mulvaney-Jones, Caroline
AU - Evans, Richard
AU - Mathialahan, Thiriloganathan
AU - Ramanaden, David
AU - Gasem, Jaber
AU - Van Duyvenvoorde, Greta
AU - Shorrock, Christopher
AU - Seward, Katie
AU - Southern, Paul
AU - Tibble, Jeremy
AU - Penn, Ruth
AU - Gorard, David
AU - Maiden, Jane
AU - Damant, Rose
AU - Palegwala, Altaf
AU - Jones, Susan
AU - Alexander, Graeme
AU - Mells, George
AU - Sandford, Richard
AU - Whiteman, Jessica
AU - Dolwani, Sunil
AU - Prince, Martin
AU - Silvestre, Valeria
AU - Foxton, Matthew
AU - Dungca, Eleanor
AU - Mitchison, Harriet
AU - Wheatley, Natalie
AU - Gooding, Ian
AU - Doyle, Helen
AU - Karmo, Mazn
AU - Kent, Melanie
AU - Saksena, Sushma
AU - Braim, Delyth
AU - Patel, Minesh
AU - Lord, Susan
AU - Ede, Roland
AU - Paton, Alison
AU - Austin, Andrew
AU - Lancaster, Nicola
AU - Sayer, Joanna
AU - Gibbins, Andrew
AU - Hogben, Karen
AU - Hovell, Chris
AU - Fisher, Neil
AU - Carter, Martyn
AU - Koss, Konrad
AU - Musselwhite, Janine
AU - Muscariu, Florin
AU - Piotreowicz, Andrzej
AU - McKay, Alexandra
AU - Grimley, Charles
AU - Neal, David
AU - Ting Tan, Lai
AU - Lim, Guan
AU - Brighton, Jacqueline
AU - Foale, Carole
AU - Ala, Aftab
AU - Saeed, Athar
AU - Flahive, Kerry
AU - Wood, Gordon
AU - Townshend, Paula
AU - Ford, Chris
AU - Brown, Jonathan
AU - Kordula, Jean
AU - Bowles, Jane
AU - Wilkinson, Mark
AU - Palmer, Caroline
AU - Ramage, John
AU - Gordon, Harriet
AU - Featherstone, James
AU - Ridpath, Jo
AU - Ngatchu, Theodore
AU - Levi, Sass
AU - Shaukat, Syed
AU - Sadeghian, Joy
AU - Shidrawi, Ray
AU - Williams, Bronwen
AU - Abouda, George
AU - Jones, Sarah
AU - Duggan, Claire
AU - Hynes, Abigail
AU - Narain, Mark
AU - Rees, Ian
AU - Salam, Imroz
AU - Crossey, Mary
AU - Taylor-Robinson, Simon
AU - Brown, Ashley
AU - MacNicol, Carolyn
AU - Williams, Simon
AU - Wilhelmsen, Elva
AU - Banim, Paul
AU - Raymode, Parizade
AU - Chilton, Andrew
AU - Das, Debasish
AU - Lee, Hye-Jeong
AU - Curtis, Howard
AU - Heneghan, Michael
AU - Gess, Markus
AU - Durant, Emma
AU - Drake, I. M.
AU - Bishop, Rebecca
AU - Davies, Mervyn
AU - Jones, Rebecca
AU - Aldersley, Mark
AU - Ncube, Noma
AU - McNair, Alistair
AU - Srirajaskanthan, Raj
AU - Sen, Sambit
AU - Casey, Rebecca
AU - Bird, George
AU - Mendall, Mike
AU - Cowley, Caroline
AU - Barnardo, Adrian
AU - Kitchen, Paul
AU - Yoong, Kevin
AU - Amore, Kelly
AU - Sirdefield, Dawn
AU - Orpe, Jacky
AU - Mathew, Ray
AU - MacFaul, George
AU - Wrigth, Aruna
AU - Shah, Amir
AU - Evans, Chris
AU - Keggans, Janie
AU - Bird, Bridget
AU - Baxter, Gwen
AU - Saha, Subrata
AU - Pollock, Katharine
AU - Hughes, Maggie
AU - Bramley, Peter
AU - Grieve, Emma
AU - Young, Karin
AU - Fraser, Andrew
AU - Mukhopadhya, Ashis
AU - Ocker, Kate
AU - Mills, Peter
AU - Hines, Francis
AU - Shallcross, Chris
AU - Wilkins, Joy
AU - Grellier, Leonie
AU - Campbell, Stewart
AU - Martin, Kirsty
AU - Bathgate, Andrew
AU - Innes, Caron
AU - Shepherd, Alan
AU - Rushbrook, Simon
AU - Valliani, Talal
AU - Przemioslo, Robert
AU - Fairlamb, Helen
AU - Macdonald, Chris
AU - Eastick, Anne
AU - Metcalf, Jane
AU - Tanqueray, Elizabeth
AU - Shmueli, Udi
AU - Holbrook, Becky
AU - Davis, Andrew
AU - Browning, Julie
AU - Naqvi, Asifabbas
AU - Walker, Kirsten
AU - Lee, Tom
AU - Verheyden, Juliette
AU - Slininger, Susan
AU - Ryder, Stephen D
AU - Chapman, Roger
AU - Collier, Jane
AU - O'Donnell, Denise
AU - Stafford, Lizzie
AU - Williamson, Kate
AU - Kent, Linda
AU - Klass, Howard
AU - Ninkovic, Mary
AU - March, Linda
AU - Cramp, Matthew
AU - Simpson, Diane
AU - Dickson, Christine
AU - Sharer, Nicholas
AU - Hayes, Maria
AU - Goggin, Patrick
AU - Quinne, Mary
AU - Pearson, Sallyanne
AU - Hoeroldt, Barbara
AU - Jones, Linda
AU - Wright, Alice
AU - Booth, Jonathan
AU - Loftus, Alison
AU - Lipscomb, George
AU - Dewhurst, Hannah
AU - Gunter, Emma
AU - Williams, Earl
AU - Fouracres, Anna
AU - Farrington, Liz
AU - Graves, Lyn
AU - Hussaini, Hyder
AU - Stableforth, Bill
AU - Marriott, Suzie
AU - Ayres, Reuben
AU - Leoni, Marina
AU - Burroughs, Andrew
AU - Marshall, Eileen
AU - Thorburn, Douglas
AU - Tyrer, David
AU - Martin, Kate
AU - Lombard, Martin
AU - Patanwala, Imran
AU - Dali-Kemmery, Lola
AU - Lambourne, Victoria
AU - Maltby, Julia
AU - Vyas, Samir
AU - Colley, Julie
AU - Shinder, Bal
AU - Singhal, Saket
AU - Jones, Jayne
AU - Mills, Marisa
AU - Gleeson, Dermot
AU - Carnahan, Mandy
AU - Butterworth, Jeff
AU - Boulton, Kerenza
AU - Taylor, Natalie
AU - George, Keith
AU - Harding, Tim
AU - Tregonning, Julie
AU - Douglass, Andrew
AU - Brown, Carly
AU - Clifford, Gayle
AU - Panter, Simon
AU - Gocher, Denise
AU - Shearman, Jeremy
AU - Bray, Gary
AU - Hamilton, Maria
AU - Butcher, Graham
AU - Forton, Daniel
AU - Mclindon, John
AU - Curtis, Janette
AU - Das, Debashis
AU - Shewan, Tracey
AU - Cowan, Matthew
AU - Whatley, Gregory
AU - Nasseri, Mariam
AU - Grover, Bob
AU - Sivaramakrishnan, Nurani
AU - Ducker, Samantha
AU - Houghton, Kathryn
AU - Jones, David
AU - Griffiths, Laura
AU - Tripoli, Sherill
AU - Pitcher, Maxton
AU - Shpuza, Ervin
AU - White, Nikki
AU - Ghosh, Deb
AU - Douds, Andrew
AU - Green, Marie
AU - Brookes, Matthew
AU - Cumlat, Lourdes
AU - Wong, Voi Shim
AU - Warner, Karen
AU - Netherton, Kimberley
AU - Mandal, Adtya
AU - Jain, Snjiv
AU - Gupta, Hemant
AU - Sanghi, Pradeep
AU - Pereira, Steve
AU - Neuberger, James
AU - Gunson, Bridget
AU - Hirschfield, Gideon
AU - Lim, Reina Teegan
AU - Gallagher, Susan
AU - Clement, Darren
AU - Brind, Alison
AU - Watts, Gill
AU - Mupudzi, Mcdonald
AU - Wright, Mark
AU - Gitahi, Jane
AU - Gordon, Fiona
AU - Gocher, Denis
AU - Unitt, Esther
AU - Pateman, Hilary
AU - Batham, Sally
AU - Delahooke, Toby
AU - Grant, Allister
AU - Conder, Jill
AU - Higham, Andrew
AU - Cox, Mark
AU - O'Donohoe, Lynn
AU - Currie, Lynn
AU - King, Alistair
AU - Oblak, Metod
AU - Collins, Carole
AU - Whalley, Simon
AU - Quinn, Marie
AU - Baird, Yolanda
AU - Amey, Isobel
AU - Fraser, Jocelyn
AU - Li, Andy
AU - Cotterill, Donna
AU - Bell, Andrew
AU - Watson, Alan
AU - Singhal, Amit
AU - Gee, Ian
AU - Greer, Sandra
AU - Ang, Yeng
AU - Ransford, Rupert
AU - Allison, Joanna
AU - Gotto, James
AU - Dyer, Simon
AU - Sweeting, Helen
AU - Millson, Charles
AU - Invernizzi, Pietro
AU - Cristoferi, Laura
AU - Bonato, Giulia
AU - Malinverno, Federica
AU - Bernuzzi, Francesca
AU - Alvaro, Domenico
AU - Labbadia, Giancarlo
AU - Bragazzi, Maria Consiglia
AU - Andreone, Pietro
AU - Muratori, Luigi
AU - Azzaroli, Francesco
AU - Floreani, Annarosa
AU - Galli, Andrea
AU - Tarocchi, Mirko
AU - Giannini, Edoardo
AU - Miele, Luca
AU - Gasbarrini, Antonio
AU - Grieco, Antonio
AU - Marrone, Giuseppe
AU - Donato, Maria Francesca
AU - Valenti, Luca
AU - Marra, Fabio
AU - Marzioni, Marco
AU - Maroni, Luca
AU - Rigamonti, Cristina
AU - Zuin, Massimo
AU - Battezzati, Pier Maria
AU - Picciotto, Antonino
PY - 2018
Y1 - 2018
N2 - 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<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79–0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=–0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present). Interpretation: We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis. Funding: UK Medical Research Council and University of Milan-Bicocca.
AB - 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<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79–0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=–0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present). Interpretation: We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis. Funding: UK Medical Research Council and University of Milan-Bicocca.
KW - Gastroenterology
KW - Hepatology
KW - Gastroenterology
KW - Hepatology
UR - https://publicatt.unicatt.it/handle/10807/134099
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85053840388&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85053840388&origin=inward
U2 - 10.1016/S2468-1253(18)30163-8
DO - 10.1016/S2468-1253(18)30163-8
M3 - Article
SN - 2468-1253
VL - 3
SP - 626
EP - 634
JO - The Lancet Gastroenterology and Hepatology
JF - The Lancet Gastroenterology and Hepatology
IS - 9
ER -