Browse by author
Lookup NU author(s): Emeritus Professor John Kirby,
Dr Deborah Stocken,
Professor Heather Cordell
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2018 Elsevier Ltd 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.
Author(s): Carbone M, Nardi A, Flack S, Carpino G, Varvaropoulou N, Gavrila C, Spicer A, Badrock J, Bernuzzi F, Cardinale V, Ainsworth HF, Heneghan MA, Thorburn D, Bathgate A, Jones R, Neuberger JM, Battezzati PM, Zuin M, Taylor-Robinson S, Donato MF, 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 DD, Cordell HJ, Hirschfield GM, Alexander GJ, Sandford RN, Jones DE, Invernizzi P, Mells GF, 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, Alexander G, Mells G, Sandford R, Whiteman J, 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, Jones S, Duggan C, Hynes A, Narain M, Rees I, Salam I, Crossey M, Taylor-Robinson S, Brown A, MacNicol C, Williams S, Wilhelmsen E, Banim P, Raymode P, Chilton A, Das D, Lee H-J, Curtis H, Heneghan M, Gess M, Durant E, Drake IM, Bishop R, Davies M, Jones R, 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, Bathgate A, 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 SD, 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, Thorburn D, Tyrer D, Martin K, 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, Das D, Shewan T, Cowan M, Whatley G, Nasseri M, Grover B, Sivaramakrishnan N, Ducker S, Houghton K, Jones D, Griffiths L, Tripoli S, Pitcher M, Shpuza E, White N, Ghosh D, Douds A, Green M, Brookes M, Cumlat L, Wong VS, Warner K, Netherton K, Mandal A, Jain S, Gupta H, Sanghi P, Pereira S, Neuberger J, Gunson B, Hirschfield G, Lim RT, Gallagher S, Clement D, Brind A, Watts G, Mupudzi M, Wright M, Gitahi J, Gordon F, Gocher D, 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, Watson A, Singhal A, Gee I, Greer S, Ang Y, Ransford R, Allison J, Gotto J, Dyer S, Sweeting H, Millson C, Invernizzi P, Carbone M, Cristoferi L, Bonato G, Malinverno F, Bernuzzi F, Alvaro D, Labbadia G, Bragazzi MC, Andreone P, Muratori L, Azzaroli F, Floreani A, Galli A, Tarocchi M, Giannini E, Miele L, Gasbarrini A, Grieco A, Marrone G, Donato MF, Valenti L, Marra F, Marzioni M, Maroni L, Rigamonti C, Zuin M, Battezzati PM, Picciotto A
Publication type: Article
Publication status: Published
Journal: The Lancet Gastroenterology and Hepatology
Print publication date: 01/09/2018
Online publication date: 13/07/2018
Acceptance date: 02/04/2018
ISSN (print): 2468-1253
Publisher: Elsevier Ltd
Altmetrics provided by Altmetric