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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.
Carbone, M., Nardi, A., Flack, S., Carpino, G., Varvaropoulou, N., Gavrila, C., Spicer, A., Badrock, J., Bernuzzi, F., Cardinale, V., Ainsworth, H. F., Heneghan, M. A., Thorburn, D., Bathgate, A., Jones, R., Neuberger, J. M., Battezzati, P. M., Zuin, M., Taylor-Robinson, S., Donato, M. F., 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. D., Cordell, H. J., Hirschfield, G. M., Alexander, G. J., Sandford, R. N., Jones, D. E., Invernizzi, P., Mells, G. F., 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., Curtis, H., Heneghan, M., Gess, M., Durant, E., Drake, I. M., 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, S. D., 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, V. S., Warner, K., Netherton, K., Mandal, A., Jain, S., Gupta, H., Sanghi, P., Pereira, S., Neuberger, J., Gunson, B., Hirschfield, G., Lim, R. T., 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., Cristoferi, L., Bonato, G., Malinverno, F., Bernuzzi, F., Alvaro, D., Labbadia, G., Bragazzi, M. C., Andreone, P., Muratori, L., Azzaroli, F., Floreani, A., Galli, A., Tarocchi, M., Giannini, E., Miele, L., Gasbarrini, A., Grieco, A., Marrone, G., Donato, M. F., Valenti, L., Marra, F., Marzioni, M., Maroni, L., Rigamonti, C., Zuin, M., Battezzati, P. M., Picciotto, A., Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score, <<THE LANCET. GASTROENTEROLOGY & HEPATOLOGY>>, 2018; 3 (9): 626-634. [doi:10.1016/S2468-1253(18)30163-8] [http://hdl.handle.net/10807/134099]
Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
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.
Carbone, M., Nardi, A., Flack, S., Carpino, G., Varvaropoulou, N., Gavrila, C., Spicer, A., Badrock, J., Bernuzzi, F., Cardinale, V., Ainsworth, H. F., Heneghan, M. A., Thorburn, D., Bathgate, A., Jones, R., Neuberger, J. M., Battezzati, P. M., Zuin, M., Taylor-Robinson, S., Donato, M. F., 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. D., Cordell, H. J., Hirschfield, G. M., Alexander, G. J., Sandford, R. N., Jones, D. E., Invernizzi, P., Mells, G. F., 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., Curtis, H., Heneghan, M., Gess, M., Durant, E., Drake, I. M., 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, S. D., 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, V. S., Warner, K., Netherton, K., Mandal, A., Jain, S., Gupta, H., Sanghi, P., Pereira, S., Neuberger, J., Gunson, B., Hirschfield, G., Lim, R. T., 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., Cristoferi, L., Bonato, G., Malinverno, F., Bernuzzi, F., Alvaro, D., Labbadia, G., Bragazzi, M. C., Andreone, P., Muratori, L., Azzaroli, F., Floreani, A., Galli, A., Tarocchi, M., Giannini, E., Miele, L., Gasbarrini, A., Grieco, A., Marrone, G., Donato, M. F., Valenti, L., Marra, F., Marzioni, M., Maroni, L., Rigamonti, C., Zuin, M., Battezzati, P. M., Picciotto, A., Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score, <<THE LANCET. GASTROENTEROLOGY & HEPATOLOGY>>, 2018; 3 (9): 626-634. [doi:10.1016/S2468-1253(18)30163-8] [http://hdl.handle.net/10807/134099]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/134099
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
