Carbone Marco, Nardi Alessandra, Flack Steve, Carpino Guido, Varvaropoulou Nikoletta, Gavrila Caius, Spicer Ann, Badrock Jonathan, Bernuzzi Francesca,
Cardinale Vincenzo, Ainsworth Holly F, Heneghan Michael A, Thorburn Douglas, 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 Fotios, 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 Chris, 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, Whiteman Jessica, 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 Chris, Fisher Neil, Carter Martyn, Koss Konrad, Musselwhite Janine, Muscariu Florin, Piotreowicz Andrzej, Mckay Alexandra, Grimley Charles, Neal David, Ting Tan Lai, Lim Guan, Brighton Jacqueline, Foale Carole, Ala Aftab, Saeed Athar, Flahive Kerry, Wood Gordon, Townshend Paula, Ford Chris, Brown Jonathan, Kordula Jean, Bowles Jane, Wilkinson Mark, Palmer Caroline, Ramage John, Gordon Harriet, Featherstone James, Ridpath Jo, Ngatchu Theodore, Levi Sass, Shaukat Syed, Sadeghian Joy, Shidrawi Ray, Williams Bronwen, Abouda George, Jones Sarah, Duggan Claire, Hynes Abigail, Narain Mark, Rees Ian, Salam Imroz, Crossey Mary, Taylor-Robinson Simon, Brown Ashley, Macnicol Carolyn, Williams Simon, Wilhelmsen Elva, Banim Paul, Raymode Parizade, Chilton Andrew, Das Debasish, Lee Hye-Jeong, Curtis Howard, Heneghan Michael, Gess Markus, Durant Emma, Drake Im, Bishop Rebecca, Davies Mervyn, Jones Rebecca, 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 Chris, Keggans Janie, Bird Bridget, Baxter Gwen, Saha Subrata, Pollock Katharine, Hughes Maggie, Bramley Peter, Grieve Emma, Young Karin, Fraser Andrew, Mukhopadhya Ashis, Ocker Kate, Mills Peter, Hines Francis, Shallcross Chris, Wilkins Joy, Grellier Leonie, Campbell Stewart, Martin Kirsty, Bathgate Andrew, Innes Caron, Shepherd Alan, Rushbrook Simon, Valliani Talal, Przemioslo Robert, Fairlamb Helen, Macdonald Chris, Eastick Anne, Metcalf Jane, Tanqueray Elizabeth, Shmueli Udi, Holbrook Becky, Davis Andrew, Browning Julie, Naqvi Asifabbas, 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,
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
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.
