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1. Influence of laparoscopic surgery on the outcomes of radical cystectomy within a multimodal rehabilitation protocol

Author

Muñiz Suárez, L., Subirá Ríos, J., Gayarre Abril, P., Montero Martorán, A., Hijazo Conejos, J.I., García Alarcón, J., García-Magariño Alonso, J., Medrano Llorente, P., Ramírez Fabián, M., Elizalde Benito, F.X., Murillo Pérez, C., Utrilla Ibuarben, M., Asensio Matas, A., Marín Zaldívar, C., Casans Francés, R., Ramírez Rodríguez, J.M., Blasco Beltrán, B., and Carrera-Lasfuentes, P.

Published
2024
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2. Influencia de la cirugía laparoscópica dentro de un protocolo de rehabilitación multimodal en cistectomía radical

Author

Muñiz Suárez, L., Subirá Ríos, J., Gayarre Abril, P., Montero Martorán, A., Hijazo Conejos, J.I., García Alarcón, J., García-Magariño Alonso, J., Medrano Llorente, P., Ramírez Fabián, M., Elizalde Benito, F.X., Murillo Pérez, C., Utrilla Ibuarben, M., Asensio Matas, A., Marín Zaldívar, C., Casans Francés, R., Ramírez Rodríguez, J.M., Blasco Beltrán, B., and Carrera-Lasfuentes, P.

Published
2024
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4. Geographical region and clinical outcomes of patients with primary biliary cholangitis from Western Europe

Author

Murillo Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van Der Meer, A, Maria Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, Lammers, W, Murillo Perez C. F., Gerussi A., Trivedi P. J., Corpechot C., Van Der Meer A. J., Maria Battezzati P., Lindor K. D., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., Tanaka A., Ma X., Mason A. L., Gulamhusein A., Ponsioen C. Y., Carbone M., Lleo A., Mayo M. J., Dalekos G. N., Gatselis N. K., Thorburn D., Verhelst X., Pares A., Janssen H. L. A., Hirschfield G. M., Hansen B. E., Invernizzi P., Lammers W. J., Murillo Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van Der Meer, A, Maria Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, Lammers, W, Murillo Perez C. F., Gerussi A., Trivedi P. J., Corpechot C., Van Der Meer A. J., Maria Battezzati P., Lindor K. D., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., Tanaka A., Ma X., Mason A. L., Gulamhusein A., Ponsioen C. Y., Carbone M., Lleo A., Mayo M. J., Dalekos G. N., Gatselis N. K., Thorburn D., Verhelst X., Pares A., Janssen H. L. A., Hirschfield G. M., Hansen B. E., Invernizzi P., and Lammers W. J.

Abstract

Background and aims The are geographic variations in the incidence and prevalence of primary biliary cholangitis (PBC). The aim was to explore whether clinical outcomes of patients within Western Europe differ according to geographical region. Methods Ursodeoxycholic acid-treated patients from European centers from the Global PBC database diagnosed from 1990 onwards were included. Patients with a time lag > 1 year from diagnosis to start of follow-up were excluded. Differences in baseline characteristics were studied according to North/South and East/West, whereas outcomes (transplant-free survival and decompensation) were studied with center latitude and longitude. Cox regression analyses were adjusted for age, sex, diagnosis year, biochemical markers, and cirrhosis as a time-dependent covariate. Results One thousand eight hundred seventy-eight patients were included, and there were no geographical differences in age or sex, with a mean age of 54 years and 89% female patients. Those in North Europe were more often of a moderately advanced/advanced Rotterdam biochemical stage (28.4%) compared with South Europe (20.6%). Additionally, they exhibited higher median alkaline phosphatase (2.0 ×ULN vs. 1.4 ×ULN) and transaminases. In multivariable analysis, there was a significant interaction between center latitude and longitude for decompensation (P < 0.001) and a trend for transplant-free survival, in which the Northwestern area demonstrated an increased risk for poor outcomes as compared to the reference (Paris). Conclusion We describe geographic variations in outcomes for patients across Europe from specialist centers in the Global PBC Study Group. Further study is important to explore the potential individual, environmental, and healthcare-related factors that may be contributors.

Published
2023

5. Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival

Author

Murillo Perez, C. Fiorella, Ioannou, Stephanie, Hassanally, Iman, Trivedi, Palak J., Corpechot, Christophe, van der Meer, Adriaan J., Lammers, Willem J., Battezzati, Pier Maria, Lindor, Keith D., Nevens, Frederik, Kowdley, Kris V., Bruns, Tony, Cazzagon, Nora, Floreani, Annarosa, Mason, Andrew L., Gulamhusein, Aliya, Ponsioen, Cyriel Y., Carbone, Marco, Lleo, Ana, Mayo, Marlyn J., Dalekos, George N., Gatselis, Nikolaos K., Thorburn, Douglas, Verhelst, Xavier, Parés, Albert, Londoño, Maria Carlota, Janssen, Harry L.A., Invernizzi, Pietro, Vuppalanchi, Raj, Hirschfield, Gideon M., Hansen, Bettina E., Levy, Cynthia, Gastroenterology & Hepatology, and Epidemiology

Abstract

Background and Aims: Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response. Methods: UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP 1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early. Conclusions: We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.

Published
2023

6. Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls

Author

Murillo Perez, C, Fisher, H, Hiu, S, Kareithi, D, Adekunle, F, Mayne, T, Malecha, E, Ness, E, van der Meer, A, Lammers, W, Trivedi, P, Battezzati, P, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Mason, A, Pares, A, Londono, M, Invernizzi, P, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Gulamhusein, A, Janssen, H, Smith, R, Flack, S, Mulcahy, V, Trauner, M, Bowlus, C, Lindor, K, Corpechot, C, Jones, D, Mells, G, Hirschfield, G, Wason, J, Hansen, B, Sturgess, R, Healey, C, Gunasekera, A, Kallis, Y, Wright, G, Mathialahan, T, Evans, R, Gasem, J, Ramanaden, D, Ward, E, Bhalme, M, Southern, P, Maggs, J, Yousif, M, Srivastava, B, Foxton, M, Collins, C, Prasad, Y, Porras-Perez, F, Yapp, T, Patel, M, Ede, R, Carte, M, Koss, K, Sattianayagam, P, Grimley, C, Tidbury, J, Mansour, D, Beckley, M, Hollywood, C, Ramag, J, Gordon, H, Ridpath, J, Grover, B, Abouda, G, Rees, I, Narain, M, Salam, I, Banim, P, Das, D, Matthews, H, Mohammed, F, Jones, R, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Hutchinson, J, Gupta, P, Shah, A, Saha, S, Pollock, K, Barclay, S, Mcdonald, N, Rushbrook, S, Przemioslo, R, Millar, A, Mitchell, S, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Cramp, M, Aspinal, R, Booth, J, Williams, E, Hussaini, H, Christie, J, Chaudhry, T, Mann, S, Ala, A, Maltby, J, Corbett, C, Singhal, S, Hoeroldt, B, Butterworth, J, Douglas, A, Sinha, R, Panter, S, Shearman, J, Bray, G, Roberts, M, Forton, D, Taylor, N, Jafar, W, Cowan, M, Ch'Ng, C, Rahman, M, Wesley, E, Jain, S, Mandal, A, Wright, M, Gordon, F, Unitt, E, Austin, A, Palegwala, A, Vemala, V, Higham, A, Fraser, J, Li, A, Ramakrishnan, S, King, A, Whalley, S, Gee, I, Keld, R, Fellows, H, Gotto, J, Millson, C, Murillo Perez C. F., Fisher H., Hiu S., Kareithi D., Adekunle F., Mayne T., Malecha E., Ness E., van der Meer A. J., Lammers W. J., Trivedi P. J., Battezzati P. M., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., Mason A. L., Pares A., Londono M. -C., Invernizzi P., Carbone M., Lleo A., Mayo M. J., Dalekos G. N., Gatselis N. K., Thorburn D., Verhelst X., Gulamhusein A., Janssen H. L. A., Smith R., Flack S., Mulcahy V., Trauner M., Bowlus C. L., Lindor K. D., Corpechot C., Jones D., Mells G., Hirschfield G. M., Wason J., Hansen B. E., Sturgess R., Healey C., Gunasekera A., Kallis Y., Wright G., Mathialahan T., Evans R., Gasem J., Ramanaden D., Ward E., Bhalme M., Southern P., Maggs J., Yousif M., Srivastava B., Foxton M., Collins C., Prasad Y., Porras-Perez F., Yapp T., Patel M., Ede R., Carte M., Koss K., Sattianayagam P., Grimley C., Tidbury J., Mansour D., Beckley M., Hollywood C., Ramag J., Gordon H., Ridpath J., Grover B., Abouda G., Rees I., Narain M., Salam I., Banim P., Das D., Matthews H., Mohammed F., Jones R., Sen S., Bird G., Prince M., Prasad G., Kitchen P., Hutchinson J., Gupta P., Shah A., Saha S., Pollock K., Barclay S., McDonald N., Rushbrook S., Przemioslo R., Millar A., Mitchell S., Davis A., Naqvi A., Lee T., Ryder S., Collier J., Cramp M., Aspinal R., Booth J., Williams E., Hussaini H., Christie J., Chaudhry T., Mann S., Ala A., Maltby J., Corbett C., Singhal S., Hoeroldt B., Butterworth J., Douglas A., Sinha R., Panter S., Shearman J., Bray G., Roberts M., Forton D., Taylor N., Jafar W., Cowan M., Ch'ng C. L., Rahman M., Wesley E., Jain S., Mandal A., Wright M., Trivedi P., Gordon F., Unitt E., Austin A., Palegwala A., Vemala V., Higham A., Fraser J., Li A., Ramakrishnan S., King A., Whalley S., Gee I., Keld R., Fellows H., Gotto J., Millson C., Murillo Perez, C, Fisher, H, Hiu, S, Kareithi, D, Adekunle, F, Mayne, T, Malecha, E, Ness, E, van der Meer, A, Lammers, W, Trivedi, P, Battezzati, P, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Mason, A, Pares, A, Londono, M, Invernizzi, P, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Gulamhusein, A, Janssen, H, Smith, R, Flack, S, Mulcahy, V, Trauner, M, Bowlus, C, Lindor, K, Corpechot, C, Jones, D, Mells, G, Hirschfield, G, Wason, J, Hansen, B, Sturgess, R, Healey, C, Gunasekera, A, Kallis, Y, Wright, G, Mathialahan, T, Evans, R, Gasem, J, Ramanaden, D, Ward, E, Bhalme, M, Southern, P, Maggs, J, Yousif, M, Srivastava, B, Foxton, M, Collins, C, Prasad, Y, Porras-Perez, F, Yapp, T, Patel, M, Ede, R, Carte, M, Koss, K, Sattianayagam, P, Grimley, C, Tidbury, J, Mansour, D, Beckley, M, Hollywood, C, Ramag, J, Gordon, H, Ridpath, J, Grover, B, Abouda, G, Rees, I, Narain, M, Salam, I, Banim, P, Das, D, Matthews, H, Mohammed, F, Jones, R, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Hutchinson, J, Gupta, P, Shah, A, Saha, S, Pollock, K, Barclay, S, Mcdonald, N, Rushbrook, S, Przemioslo, R, Millar, A, Mitchell, S, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Cramp, M, Aspinal, R, Booth, J, Williams, E, Hussaini, H, Christie, J, Chaudhry, T, Mann, S, Ala, A, Maltby, J, Corbett, C, Singhal, S, Hoeroldt, B, Butterworth, J, Douglas, A, Sinha, R, Panter, S, Shearman, J, Bray, G, Roberts, M, Forton, D, Taylor, N, Jafar, W, Cowan, M, Ch'Ng, C, Rahman, M, Wesley, E, Jain, S, Mandal, A, Wright, M, Gordon, F, Unitt, E, Austin, A, Palegwala, A, Vemala, V, Higham, A, Fraser, J, Li, A, Ramakrishnan, S, King, A, Whalley, S, Gee, I, Keld, R, Fellows, H, Gotto, J, Millson, C, Murillo Perez C. F., Fisher H., Hiu S., Kareithi D., Adekunle F., Mayne T., Malecha E., Ness E., van der Meer A. J., Lammers W. J., Trivedi P. J., Battezzati P. M., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., Mason A. L., Pares A., Londono M. -C., Invernizzi P., Carbone M., Lleo A., Mayo M. J., Dalekos G. N., Gatselis N. K., Thorburn D., Verhelst X., Gulamhusein A., Janssen H. L. A., Smith R., Flack S., Mulcahy V., Trauner M., Bowlus C. L., Lindor K. D., Corpechot C., Jones D., Mells G., Hirschfield G. M., Wason J., Hansen B. E., Sturgess R., Healey C., Gunasekera A., Kallis Y., Wright G., Mathialahan T., Evans R., Gasem J., Ramanaden D., Ward E., Bhalme M., Southern P., Maggs J., Yousif M., Srivastava B., Foxton M., Collins C., Prasad Y., Porras-Perez F., Yapp T., Patel M., Ede R., Carte M., Koss K., Sattianayagam P., Grimley C., Tidbury J., Mansour D., Beckley M., Hollywood C., Ramag J., Gordon H., Ridpath J., Grover B., Abouda G., Rees I., Narain M., Salam I., Banim P., Das D., Matthews H., Mohammed F., Jones R., Sen S., Bird G., Prince M., Prasad G., Kitchen P., Hutchinson J., Gupta P., Shah A., Saha S., Pollock K., Barclay S., McDonald N., Rushbrook S., Przemioslo R., Millar A., Mitchell S., Davis A., Naqvi A., Lee T., Ryder S., Collier J., Cramp M., Aspinal R., Booth J., Williams E., Hussaini H., Christie J., Chaudhry T., Mann S., Ala A., Maltby J., Corbett C., Singhal S., Hoeroldt B., Butterworth J., Douglas A., Sinha R., Panter S., Shearman J., Bray G., Roberts M., Forton D., Taylor N., Jafar W., Cowan M., Ch'ng C. L., Rahman M., Wesley E., Jain S., Mandal A., Wright M., Trivedi P., Gordon F., Unitt E., Austin A., Palegwala A., Vemala V., Higham A., Fraser J., Li A., Ramakrishnan S., King A., Whalley S., Gee I., Keld R., Fellows H., Gotto J., and Millson C.

Abstract

Background & Aims: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA–treated external controls. Methods: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. Results: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10–0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12–0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03–1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09–1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21–0.85) including hepatic decompensation. Conclusions: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Published
2022

7. Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls

Author

Murillo Perez, C. Fiorella, primary, Fisher, Holly, additional, Hiu, Shaun, additional, Kareithi, Dorcas, additional, Adekunle, Femi, additional, Mayne, Tracy, additional, Malecha, Elizabeth, additional, Ness, Erik, additional, van der Meer, Adriaan J., additional, Lammers, Willem J., additional, Trivedi, Palak J., additional, Battezzati, Pier Maria, additional, Nevens, Frederik, additional, Kowdley, Kris V., additional, Bruns, Tony, additional, Cazzagon, Nora, additional, Floreani, Annarosa, additional, Mason, Andrew L., additional, Parés, Albert, additional, Londoño, Maria-Carlota, additional, Invernizzi, Pietro, additional, Carbone, Marco, additional, Lleo, Ana, additional, Mayo, Marlyn J., additional, Dalekos, George N., additional, Gatselis, Nikolaos K., additional, Thorburn, Douglas, additional, Verhelst, Xavier, additional, Gulamhusein, Aliya, additional, Janssen, Harry L.A., additional, Smith, Rachel, additional, Flack, Steve, additional, Mulcahy, Victoria, additional, Trauner, Michael, additional, Bowlus, Christopher L., additional, Lindor, Keith D., additional, Corpechot, Christophe, additional, Jones, David, additional, Mells, George, additional, Hirschfield, Gideon M., additional, Wason, James, additional, Hansen, Bettina E., additional, Sturgess, Richard, additional, Healey, Christopher, additional, Gunasekera, Anton, additional, Kallis, Yiannis, additional, Wright, Gavin, additional, Mathialahan, Thiriloganathan, additional, Evans, Richard, additional, Gasem, Jaber, additional, Ramanaden, David, additional, Ward, Emma, additional, Bhalme, Mahesh, additional, Southern, Paul, additional, Maggs, James, additional, Yousif, Mohamed, additional, Srivastava, Brijesh, additional, Foxton, Matthew, additional, Collins, Carole, additional, Prasad, Yash, additional, Porras-Perez, Francisco, additional, Yapp, Tom, additional, Patel, Minesh, additional, Ede, Roland, additional, Carte, Martyn, additional, Koss, Konrad, additional, Sattianayagam, Prayman, additional, Grimley, Charles, additional, Tidbury, Jude, additional, Mansour, Dina, additional, Beckley, Matilda, additional, Hollywood, Coral, additional, Ramag, John, additional, Gordon, Harriet, additional, Ridpath, Joanne, additional, Grover, Bob, additional, Abouda, George, additional, Rees, Ian, additional, Narain, Mark, additional, Salam, Imroz, additional, Banim, Paul, additional, Das, Debasish, additional, Matthews, Helen, additional, Mohammed, Faiyaz, additional, Jones, Rebecca, additional, Sen, Sambit, additional, Bird, George, additional, Prince, Martin, additional, Prasad, Geeta, additional, Kitchen, Paul, additional, Hutchinson, John, additional, Gupta, Prakash, additional, Shah, Amir, additional, Saha, Subrata, additional, Pollock, Katharine, additional, Barclay, Stephen, additional, McDonald, Natasha, additional, Rushbrook, Simon, additional, Przemioslo, Robert, additional, Millar, Andrew, additional, Mitchell, Steven, additional, Davis, Andrew, additional, Naqvi, Asifabbas, additional, Lee, Tom, additional, Ryder, Stephen, additional, Collier, Jane, additional, Cramp, Matthew, additional, Aspinal, Richard, additional, Booth, Jonathan, additional, Williams, Earl, additional, Hussaini, Hyder, additional, Christie, John, additional, Chaudhry, Tehreem, additional, Mann, Stephen, additional, Ala, Aftab, additional, Maltby, Julia, additional, Corbett, Chris, additional, Singhal, Saket, additional, Hoeroldt, Barbara, additional, Butterworth, Jeff, additional, Douglas, Andrew, additional, Sinha, Rohit, additional, Panter, Simon, additional, Shearman, Jeremy, additional, Bray, Gary, additional, Roberts, Michael, additional, Forton, Daniel, additional, Taylor, Nicola, additional, Jafar, Wisam, additional, Cowan, Matthew, additional, Ch'ng, Chin Lye, additional, Rahman, Mesbah, additional, Wesley, Emma, additional, Jain, Sanjiv, additional, Mandal, Aditya, additional, Wright, Mark, additional, Trivedi, Palak, additional, Gordon, Fiona, additional, Unitt, Esther, additional, Austin, Andrew, additional, Palegwala, Altaf, additional, Vemala, Vishwaraj, additional, Higham, Andrew, additional, Fraser, Jocelyn, additional, Li, Andy, additional, Ramakrishnan, Subramaniam, additional, King, Alistair, additional, Whalley, Simon, additional, Gee, Ian, additional, Keld, Richard, additional, Fellows, Helen, additional, Gotto, James, additional, and Millson, Charles, additional

Published
2022
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8. Simplified care-pathway selection for nonspecialist practice: the GLOBAL Primary Biliary Cholangitis Study Group Age, Bilirubin, Alkaline phosphatase risk assessment tool

Author

Murillo Perez, C, Gulamhusein, A, Carbone, M, Trivedi, P, van der Meer, A, Corpechot, C, Battezzati, P, Lammers, W, Cazzagon, N, Floreani, A, Pares, A, Nevens, F, Lleo, A, Mayo, M, Kowdley, K, Ponsioen, C, Dalekos, G, Gatselis, N, Thorburn, D, Mason, A, Janssen, H, Verhelst, X, Bruns, T, Lindor, K, Chazouilleres, O, Invernizzi, P, Hansen, B, Hirschfield, G, Murillo Perez C. F., Gulamhusein A., Carbone M., Trivedi P. J., van der Meer A. J., Corpechot C., Battezzati P. M., Lammers W. J., Cazzagon N., Floreani A., Pares A., Nevens F., Lleo A., Mayo M. J., Kowdley K. V., Ponsioen C. Y., Dalekos G. N., Gatselis N. K., Thorburn D., Mason A. L., Janssen H., Verhelst X., Bruns T., Lindor K. D., Chazouilleres O., Invernizzi P., Hansen B. E., Hirschfield G. M., Murillo Perez, C, Gulamhusein, A, Carbone, M, Trivedi, P, van der Meer, A, Corpechot, C, Battezzati, P, Lammers, W, Cazzagon, N, Floreani, A, Pares, A, Nevens, F, Lleo, A, Mayo, M, Kowdley, K, Ponsioen, C, Dalekos, G, Gatselis, N, Thorburn, D, Mason, A, Janssen, H, Verhelst, X, Bruns, T, Lindor, K, Chazouilleres, O, Invernizzi, P, Hansen, B, Hirschfield, G, Murillo Perez C. F., Gulamhusein A., Carbone M., Trivedi P. J., van der Meer A. J., Corpechot C., Battezzati P. M., Lammers W. J., Cazzagon N., Floreani A., Pares A., Nevens F., Lleo A., Mayo M. J., Kowdley K. V., Ponsioen C. Y., Dalekos G. N., Gatselis N. K., Thorburn D., Mason A. L., Janssen H., Verhelst X., Bruns T., Lindor K. D., Chazouilleres O., Invernizzi P., Hansen B. E., and Hirschfield G. M.

Abstract

BACKGROUND: Opportunity to redefine the care journeys for those living with primary biliary cholangitis (PBC) includes facilitating access to enhanced (PBC-dedicated) programmes by nonspecialist risk 'flagging' of patients. OBJECTIVE: To develop a nonexpert PBC stratification tool to help care pathway choices (standard vs. enhanced) choices in PBC. METHODS: We included ursodeoxycholic acid-treated patients with PBC from the Global PBC Study Group. The performance of baseline and 1-year clinical markers with transplant-free survival was assessed to develop the 'ABA' tool using Age (A), Bilirubin (B), and Alkaline phosphatase (A). Added value of fibrosis estimation was assessed. RESULTS: 'ABA' classification mapped three risk groups (n = 2226): low [Age > 50 years, bilirubin ≤ 1 × ULN, alkaline phosphatase (ALP) ≤ 3 × ULN], high (Age ≤ 50 years, bilirubin > 1 × ULN, ALP > 3 × ULN), and intermediate (other). Transplant-free survival at 10 years in the low-, intermediate-, and high-risk groups were 89, 77, and 59% at baseline and 86, 76, and 40% at 1 year, respectively. We propose that high-risk patients at baseline be directly triaged to enhanced (PBC-dedicated) care and the remaining be reassessed at 1 year. Modelling showed after 1 year 46% patients were proposed to enhanced care and 54% to standard care. The 'ABA' mapped pathways facilitated identification of patients at risk based on a young age, as compared to traditional liver biochemical stratification. In patients proposed to standard care, estimated fibrosis stage had ongoing prognostic value. CONCLUSION: Nonspecialist use of the 'ABA' risk tool could prioritize care journey choices for patients with PBC.

Published
2021

9. A Comparison of Prognostic Scores (Mayo, UK-PBC, and GLOBE) in Primary Biliary Cholangitis

Author

Goet, J, Murillo Perez, C, Harms, M, Floreani, A, Cazzagon, N, Bruns, T, Prechter, F, Dalekos, G, Verhelst, X, Gatselis, N, Lindor, K, Lammers, W, Gulamhusein, A, Reig, A, Carbone, M, Nevens, F, Hirschfield, G, van der Meer, A, van Buuren, H, Hansen, B, Pares, A, Goet J. C., Murillo Perez C. F., Harms M. H., Floreani A., Cazzagon N., Bruns T., Prechter F., Dalekos G. N., Verhelst X., Gatselis N. K., Lindor K. D., Lammers W. J., Gulamhusein A., Reig A., Carbone M., Nevens F., Hirschfield G. M., van der Meer A. J., van Buuren H. R., Hansen B. E., Pares A., Goet, J, Murillo Perez, C, Harms, M, Floreani, A, Cazzagon, N, Bruns, T, Prechter, F, Dalekos, G, Verhelst, X, Gatselis, N, Lindor, K, Lammers, W, Gulamhusein, A, Reig, A, Carbone, M, Nevens, F, Hirschfield, G, van der Meer, A, van Buuren, H, Hansen, B, Pares, A, Goet J. C., Murillo Perez C. F., Harms M. H., Floreani A., Cazzagon N., Bruns T., Prechter F., Dalekos G. N., Verhelst X., Gatselis N. K., Lindor K. D., Lammers W. J., Gulamhusein A., Reig A., Carbone M., Nevens F., Hirschfield G. M., van der Meer A. J., van Buuren H. R., Hansen B. E., and Pares A.

Abstract

INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.

Published
2021

10. Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls

Author

Murillo Perez, C. Fiorella, Fisher, Holly, Hiu, Shaun, Kareithi, Dorcas, Adekunle, Femi, Mayne, Tracy, Malecha, Elizabeth, Ness, Erik, van der Meer, Adriaan J., Lammers, Willem J., Trivedi, Palak J., Battezzati, Pier Maria, Nevens, Frederik, Kowdley, Kris V., Bruns, Tony, Cazzagon, Nora, Floreani, Annarosa, Mason, Andrew L., Parés, Albert, Londoño, Maria Carlota, Invernizzi, Pietro, Carbone, Marco, Lleo, Ana, Mayo, Marlyn J., Dalekos, George N., Gatselis, Nikolaos K., Thorburn, Douglas, Verhelst, Xavier, Gulamhusein, Aliya, Janssen, Harry L.A., Smith, Rachel, Flack, Steve, Mulcahy, Victoria, Trauner, Michael, Bowlus, Christopher L., Lindor, Keith D., Corpechot, Christophe, Jones, David, Mells, George, Hirschfield, Gideon M., Wason, James, Hansen, Bettina E., Murillo Perez, C. Fiorella, Fisher, Holly, Hiu, Shaun, Kareithi, Dorcas, Adekunle, Femi, Mayne, Tracy, Malecha, Elizabeth, Ness, Erik, van der Meer, Adriaan J., Lammers, Willem J., Trivedi, Palak J., Battezzati, Pier Maria, Nevens, Frederik, Kowdley, Kris V., Bruns, Tony, Cazzagon, Nora, Floreani, Annarosa, Mason, Andrew L., Parés, Albert, Londoño, Maria Carlota, Invernizzi, Pietro, Carbone, Marco, Lleo, Ana, Mayo, Marlyn J., Dalekos, George N., Gatselis, Nikolaos K., Thorburn, Douglas, Verhelst, Xavier, Gulamhusein, Aliya, Janssen, Harry L.A., Smith, Rachel, Flack, Steve, Mulcahy, Victoria, Trauner, Michael, Bowlus, Christopher L., Lindor, Keith D., Corpechot, Christophe, Jones, David, Mells, George, Hirschfield, Gideon M., Wason, James, and Hansen, Bettina E.

Abstract

Background & Aims: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA–treated external controls. Methods: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. Results: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10–0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12–0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03–1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09–1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21–0.85) including hepatic decompensation. Conclusions: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Published
2022

11. Fibrosis stage is an independent predictor of outcome in primary biliary cholangitis despite biochemical treatment response

Author

Murillo Perez, C, Hirschfield, G, Corpechot, C, Floreani, A, Mayo, M, van der Meer, A, Ponsioen, C, Lammers, W, Pares, A, Invernizzi, P, Carbone, M, Maria Battezzati, P, Nevens, F, Kowdley, K, Thorburn, D, Mason, A, Trivedi, P, Lindor, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Janssen, H, Hansen, B, Gulamhusein, A, Murillo Perez C. F., Hirschfield G. M., Corpechot C., Floreani A., Mayo M. J., van der Meer A., Ponsioen C. Y., Lammers W. J., Pares A., Invernizzi P., Carbone M., Maria Battezzati P., Nevens F., Kowdley K. V., Thorburn D., Mason A. L., Trivedi P. J., Lindor K. D., Bruns T., Dalekos G. N., Gatselis N. K., Verhelst X., Janssen H. L. A., Hansen B. E., Gulamhusein A., Murillo Perez, C, Hirschfield, G, Corpechot, C, Floreani, A, Mayo, M, van der Meer, A, Ponsioen, C, Lammers, W, Pares, A, Invernizzi, P, Carbone, M, Maria Battezzati, P, Nevens, F, Kowdley, K, Thorburn, D, Mason, A, Trivedi, P, Lindor, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Janssen, H, Hansen, B, Gulamhusein, A, Murillo Perez C. F., Hirschfield G. M., Corpechot C., Floreani A., Mayo M. J., van der Meer A., Ponsioen C. Y., Lammers W. J., Pares A., Invernizzi P., Carbone M., Maria Battezzati P., Nevens F., Kowdley K. V., Thorburn D., Mason A. L., Trivedi P. J., Lindor K. D., Bruns T., Dalekos G. N., Gatselis N. K., Verhelst X., Janssen H. L. A., Hansen B. E., and Gulamhusein A.

Abstract

Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long-term outcomes in the context of biochemical risk stratification. Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris-II criteria), as well as non-invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB-4), for transplant-free survival was assessed with Cox proportional-hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fibrosis (stage 3/4) was an independent predictor of survival in addition to non-invasive measures of fibrosis with the hazard ratios ranging from 1.59 to 2.73 (P <.001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treatment response, with a 10-year survival of 76.0%-86.6% compared to 94.5%-95.1% depending on the treatment response criteria used. Poor correlations were observed between non-invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochemical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.

Published
2019

12. Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase

Author

Murillo Perez, C, Harms, M, Lindor, K, van Buuren, H, Hirschfield, G, Corpechot, C, van der Meer, A, Feld, J, Gulamhusein, A, Lammers, W, Ponsioen, C, Carbone, M, Mason, A, Mayo, M, Invernizzi, P, Battezzati, P, Floreani, A, Lleo, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Thorburn, D, Trivedi, P, Verhelst, X, Parés, A, Janssen, H, Hansen, B, Murillo Perez, Carla F, Harms, Maren H, Lindor, Keith D, van Buuren, Henk R, Hirschfield, Gideon M, Corpechot, Christophe, van der Meer, Adriaan J, Feld, Jordan J, Gulamhusein, Aliya, Lammers, Willem J, Ponsioen, Cyriel Y, Carbone, Marco, Mason, Andrew L, Mayo, Marlyn J, Invernizzi, Pietro, Battezzati, Pier Maria, Floreani, Annarosa, Lleo, Ana, Nevens, Frederik, Kowdley, Kris V, Bruns, Tony, Dalekos, George N, Gatselis, Nikolaos K, Thorburn, Douglas, Trivedi, Palak J, Verhelst, Xavier, Parés, Albert, Janssen, Harry L A, Hansen, Bettina E, Murillo Perez, C, Harms, M, Lindor, K, van Buuren, H, Hirschfield, G, Corpechot, C, van der Meer, A, Feld, J, Gulamhusein, A, Lammers, W, Ponsioen, C, Carbone, M, Mason, A, Mayo, M, Invernizzi, P, Battezzati, P, Floreani, A, Lleo, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Thorburn, D, Trivedi, P, Verhelst, X, Parés, A, Janssen, H, Hansen, B, Murillo Perez, Carla F, Harms, Maren H, Lindor, Keith D, van Buuren, Henk R, Hirschfield, Gideon M, Corpechot, Christophe, van der Meer, Adriaan J, Feld, Jordan J, Gulamhusein, Aliya, Lammers, Willem J, Ponsioen, Cyriel Y, Carbone, Marco, Mason, Andrew L, Mayo, Marlyn J, Invernizzi, Pietro, Battezzati, Pier Maria, Floreani, Annarosa, Lleo, Ana, Nevens, Frederik, Kowdley, Kris V, Bruns, Tony, Dalekos, George N, Gatselis, Nikolaos K, Thorburn, Douglas, Trivedi, Palak J, Verhelst, Xavier, Parés, Albert, Janssen, Harry L A, and Hansen, Bettina E

Abstract

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.

Published
2020

13. Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Author

Cheung, A, Lammers, W, Murillo Perez, C, van Buuren, H, Gulamhusein, A, Trivedi, P, Lazaridis, K, Ponsioen, C, Floreani, A, Hirschfield, G, Corpechot, C, Mayo, M, Invernizzi, P, Battezzati, P, Parés, A, Nevens, F, Thorburn, D, Mason, A, Carbone, M, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Lindor, K, Lleo, A, Poupon, R, Janssen, H, Hansen, B, Cheung, Angela C, Lammers, Willem J, Murillo Perez, Carla F, van Buuren, Henk R, Gulamhusein, Aliya, Trivedi, Palak J, Lazaridis, Konstantinos N, Ponsioen, Cyriel Y, Floreani, Annarosa, Hirschfield, Gideon M, Corpechot, Christophe, Mayo, Marlyn J, Invernizzi, Pietro, Battezzati, Pier Maria, Parés, Albert, Nevens, Frederik, Thorburn, Douglas, Mason, Andrew L, Carbone, Marco, Kowdley, Kris V, Bruns, Tony, Dalekos, George N, Gatselis, Nikolaos K, Verhelst, Xavier, Lindor, Keith D, Lleo, Ana, Poupon, Raoul, Janssen, Harry L, Hansen, Bettina E, Cheung, A, Lammers, W, Murillo Perez, C, van Buuren, H, Gulamhusein, A, Trivedi, P, Lazaridis, K, Ponsioen, C, Floreani, A, Hirschfield, G, Corpechot, C, Mayo, M, Invernizzi, P, Battezzati, P, Parés, A, Nevens, F, Thorburn, D, Mason, A, Carbone, M, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Lindor, K, Lleo, A, Poupon, R, Janssen, H, Hansen, B, Cheung, Angela C, Lammers, Willem J, Murillo Perez, Carla F, van Buuren, Henk R, Gulamhusein, Aliya, Trivedi, Palak J, Lazaridis, Konstantinos N, Ponsioen, Cyriel Y, Floreani, Annarosa, Hirschfield, Gideon M, Corpechot, Christophe, Mayo, Marlyn J, Invernizzi, Pietro, Battezzati, Pier Maria, Parés, Albert, Nevens, Frederik, Thorburn, Douglas, Mason, Andrew L, Carbone, Marco, Kowdley, Kris V, Bruns, Tony, Dalekos, George N, Gatselis, Nikolaos K, Verhelst, Xavier, Lindor, Keith D, Lleo, Ana, Poupon, Raoul, Janssen, Harry L, and Hansen, Bettina E

Abstract

Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival.

Published
2019

14. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history

Author

Murillo Perez, C, Goet, J, Lammers, W, Gulamhusein, A, van Buuren, H, Ponsioen, C, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Thorburn, D, Hirschfield, G, Larusso, N, Lindor, K, Zachou, K, Poupon, R, Trivedi, P, Verhelst, X, Janssen, H, Hansen, B, Murillo Perez, Carla F., Goet, Jorn C., Lammers, Willem J., Gulamhusein, Aliya, van Buuren, Henk R., Ponsioen, Cyriel Y., Carbone, Marco, Mason, Andrew, Corpechot, Christophe, Invernizzi, Pietro, Mayo, Marlyn J., Battezzati, Pier Maria, Floreani, Annarosa, Pares, Albert, Nevens, Frederik, Kowdley, Kris V., Bruns, Tony, Dalekos, George N., Thorburn, Douglas, Hirschfield, Gideon, LaRusso, Nicholas F., Lindor, Keith D., Zachou, Kalliopi, Poupon, Raoul, Trivedi, Palak J., Verhelst, Xavier, Janssen, Harry L. A., Hansen, Bettina E., Murillo Perez, C, Goet, J, Lammers, W, Gulamhusein, A, van Buuren, H, Ponsioen, C, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Thorburn, D, Hirschfield, G, Larusso, N, Lindor, K, Zachou, K, Poupon, R, Trivedi, P, Verhelst, X, Janssen, H, Hansen, B, Murillo Perez, Carla F., Goet, Jorn C., Lammers, Willem J., Gulamhusein, Aliya, van Buuren, Henk R., Ponsioen, Cyriel Y., Carbone, Marco, Mason, Andrew, Corpechot, Christophe, Invernizzi, Pietro, Mayo, Marlyn J., Battezzati, Pier Maria, Floreani, Annarosa, Pares, Albert, Nevens, Frederik, Kowdley, Kris V., Bruns, Tony, Dalekos, George N., Thorburn, Douglas, Hirschfield, Gideon, LaRusso, Nicholas F., Lindor, Keith D., Zachou, Kalliopi, Poupon, Raoul, Trivedi, Palak J., Verhelst, Xavier, Janssen, Harry L. A., and Hansen, Bettina E.

Abstract

Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9 ± 10.1 years in the 1970s to 57.0 ± 12.1 years from 2010 onward (P < 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; P < 0.001). Conclusion: In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. (Hepatology 2018;67:1

Published
2018

18. Geographical region and clinical outcomes of patients with primary biliary cholangitis from Western Europe

Author

Carla F, Murillo Perez, Alessio, Gerussi, Palak J, Trivedi, Christophe, Corpechot, Adriaan J, van der Meer, Pier, Maria Battezzati, Keith D, Lindor, Frederik, Nevens, Kris V, Kowdley, Tony, Bruns, Nora, Cazzagon, Annarosa, Floreani, Atsushi, Tanaka, Xiong, Ma, Andrew L, Mason, Aliya, Gulamhusein, Cyriel Y, Ponsioen, Marco, Carbone, Ana, Lleo, Marlyn J, Mayo, George N, Dalekos, Nikolaos K, Gatselis, Douglas, Thorburn, Xavier, Verhelst, Albert, Parés, Harry L A, Janssen, Gideon M, Hirschfield, Bettina E, Hansen, Pietro, Invernizzi, Willem J, Lammers, Gastroenterology & Hepatology, Murillo Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van Der Meer, A, Maria Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, and Lammers, W

Subjects
Male, Europe, Liver Cirrhosis, Databases, Factual, risk factor, Liver Cirrhosis, Biliary, environmental factor, Graft Survival, Humans, Female, Middle Aged, geography
Abstract

Background and aims The are geographic variations in the incidence and prevalence of primary biliary cholangitis (PBC). The aim was to explore whether clinical outcomes of patients within Western Europe differ according to geographical region. Methods Ursodeoxycholic acid-treated patients from European centers from the Global PBC database diagnosed from 1990 onwards were included. Patients with a time lag > 1 year from diagnosis to start of follow-up were excluded. Differences in baseline characteristics were studied according to North/South and East/West, whereas outcomes (transplant-free survival and decompensation) were studied with center latitude and longitude. Cox regression analyses were adjusted for age, sex, diagnosis year, biochemical markers, and cirrhosis as a time-dependent covariate. Results One thousand eight hundred seventy-eight patients were included, and there were no geographical differences in age or sex, with a mean age of 54 years and 89% female patients. Those in North Europe were more often of a moderately advanced/advanced Rotterdam biochemical stage (28.4%) compared with South Europe (20.6%). Additionally, they exhibited higher median alkaline phosphatase (2.0 ×ULN vs. 1.4 ×ULN) and transaminases. In multivariable analysis, there was a significant interaction between center latitude and longitude for decompensation (P < 0.001) and a trend for transplant-free survival, in which the Northwestern area demonstrated an increased risk for poor outcomes as compared to the reference (Paris). Conclusion We describe geographic variations in outcomes for patients across Europe from specialist centers in the Global PBC Study Group. Further study is important to explore the potential individual, environmental, and healthcare-related factors that may be contributors.

Published
2023

19. Simplified care-pathway selection for nonspecialist practice

Author

Aliya Gulamhusein, Nora Cazzagon, Xavier Verhelst, Andrew Mason, Cyriel Y. Ponsioen, George N. Dalekos, Keith D. Lindor, Frederik Nevens, Palak J. Trivedi, Adriaan J. van der Meer, Kris V. Kowdley, Willem J Lammers, Olivier Chazouillères, Ana Lleo, Douglas Thorburn, Nikolaos K. Gatselis, Bettina E. Hansen, Carla F. Murillo Perez, Tony Bruns, Gideon M. Hirschfield, Pietro Invernizzi, Annarosa Floreani, Christophe Corpechot, Marco Carbone, Marlyn J. Mayo, Albert Parés, Pier Maria Battezzati, Harry L.A. Janssen, Gastroenterology & Hepatology, Murillo Perez, C, Gulamhusein, A, Carbone, M, Trivedi, P, van der Meer, A, Corpechot, C, Battezzati, P, Lammers, W, Cazzagon, N, Floreani, A, Pares, A, Nevens, F, Lleo, A, Mayo, M, Kowdley, K, Ponsioen, C, Dalekos, G, Gatselis, N, Thorburn, D, Mason, A, Janssen, H, Verhelst, X, Bruns, T, Lindor, K, Chazouilleres, O, Invernizzi, P, Hansen, B, Hirschfield, G, Gastroenterology and Hepatology, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Cholagogues and Choleretics, medicine.medical_specialty, Bilirubin, Risk management tools, Risk Assessment, chemistry.chemical_compound, Risk groups, Internal medicine, medicine, Care pathway, Humans, In patient, Hepatology, Liver Cirrhosis, Biliary, business.industry, Ursodeoxycholic Acid, Gastroenterology, Fibrosis stage, Middle Aged, Alkaline Phosphatase, pbc, Young age, chemistry, Critical Pathways, Alkaline phosphatase, business
Abstract

BACKGROUND: Opportunity to redefine the care journeys for those living with primary biliary cholangitis (PBC) includes facilitating access to enhanced (PBC-dedicated) programmes by nonspecialist risk 'flagging' of patients. OBJECTIVE: To develop a nonexpert PBC stratification tool to help care pathway choices (standard vs. enhanced) choices in PBC. METHODS: We included ursodeoxycholic acid-treated patients with PBC from the Global PBC Study Group. The performance of baseline and 1-year clinical markers with transplant-free survival was assessed to develop the 'ABA' tool using Age (A), Bilirubin (B), and Alkaline phosphatase (A). Added value of fibrosis estimation was assessed. RESULTS: 'ABA' classification mapped three risk groups (n = 2226): low [Age > 50 years, bilirubin ≤ 1 × ULN, alkaline phosphatase (ALP) ≤ 3 × ULN], high (Age ≤ 50 years, bilirubin > 1 × ULN, ALP > 3 × ULN), and intermediate (other). Transplant-free survival at 10 years in the low-, intermediate-, and high-risk groups were 89, 77, and 59% at baseline and 86, 76, and 40% at 1 year, respectively. We propose that high-risk patients at baseline be directly triaged to enhanced (PBC-dedicated) care and the remaining be reassessed at 1 year. Modelling showed after 1 year 46% patients were proposed to enhanced care and 54% to standard care. The 'ABA' mapped pathways facilitated identification of patients at risk based on a young age, as compared to traditional liver biochemical stratification. In patients proposed to standard care, estimated fibrosis stage had ongoing prognostic value. CONCLUSION: Nonspecialist use of the 'ABA' risk tool could prioritize care journey choices for patients with PBC.

Published
2021

20. Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase

Author

George N. Dalekos, Harry L.A. Janssen, Albert Parés, Willem J Lammers, Keith D. Lindor, Frederik Nevens, Jordan J. Feld, Maren H. Harms, Pier Maria Battezzati, Henk R. van Buuren, Marlyn J. Mayo, Pietro Invernizzi, Carla F. Murillo Perez, Christophe Corpechot, Annarosa Floreani, Douglas Thorburn, Tony Bruns, Palak J. Trivedi, Kris V. Kowdley, Xavier Verhelst, Ana Lleo, Aliya Gulamhusein, Cyriel Y. Ponsioen, Nikolaos K. Gatselis, Andrew Mason, Bettina E. Hansen, Gideon M. Hirschfield, Adriaan J. van der Meer, Marco Carbone, Murillo Perez, C, Harms, M, Lindor, K, van Buuren, H, Hirschfield, G, Corpechot, C, van der Meer, A, Feld, J, Gulamhusein, A, Lammers, W, Ponsioen, C, Carbone, M, Mason, A, Mayo, M, Invernizzi, P, Battezzati, P, Floreani, A, Lleo, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Thorburn, D, Trivedi, P, Verhelst, X, Parés, A, Janssen, H, Hansen, B, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology & Hepatology

Subjects
Male, medicine.medical_specialty, Cholagogues and Choleretics, Cirrhosis, Bilirubin, Cholangitis, medicine.medical_treatment, Autoimmune hepatitis, Liver transplantation, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, Reference Values, Internal medicine, medicine, Humans, Primary Biliary Cholangiti, Survival rate, Hepatology, business.industry, Hazard ratio, Ursodeoxycholic Acid, Middle Aged, medicine.disease, Alkaline Phosphatase, Prognosis, Survival Rate, chemistry, 030220 oncology & carcinogenesis, Cohort, Alkaline phosphatase, 030211 gastroenterology & hepatology, Female, business, Biomarkers
Abstract

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.

Published
2020
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21. A Comparison of Prognostic Scores (Mayo, UK-PBC, and GLOBE) in Primary Biliary Cholangitis

Author

Gideon M. Hirschfield, Carla F. Murillo Perez, Frederik Nevens, Jorn C Goet, Keith D Lindor, Albert Parés, Nora Cazzagon, Nikolaos K. Gatselis, Annarosa Floreani, Anna Reig, Willem J Lammers, Florian Prechter, George N. Dalekos, Marco Carbone, Bettina E. Hansen, Maren H. Harms, Henk R. van Buuren, Tony Bruns, Adriaan J. van der Meer, Aliya Gulamhusein, Xavier Verhelst, Gastroenterology & Hepatology, Goet, J, Murillo Perez, C, Harms, M, Floreani, A, Cazzagon, N, Bruns, T, Prechter, F, Dalekos, G, Verhelst, X, Gatselis, N, Lindor, K, Lammers, W, Gulamhusein, A, Reig, A, Carbone, M, Nevens, F, Hirschfield, G, van der Meer, A, van Buuren, H, Hansen, B, and Pares, A

Subjects
Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Concordance, medicine.medical_treatment, Liver transplantation, Severity of Illness Index, Cohort Studies, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Cholagogues and Choleretic, Aged, Hyperbilirubinemia, Framingham Risk Score, Hepatology, business.industry, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Gastroenterology, Middle Aged, medicine.disease, Prognosis, Confidence interval, Advanced fibrosis, Liver Transplantation, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, Cohort Studie, business, Human
Abstract

INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.

Published
2021

22. Fibrosis stage is an independent predictor of outcome in primary biliary cholangitis despite biochemical treatment response

Author

Murillo Perez, Fiorella, Hirschfield, GM, Corpechot, C, Floreani, A, Mayo, MJ, van der Meer, Adriaan, Ponsioen, CY, Lammers, Wim, Pares, A, Invernizzi, P, Carbone, M, Battezzati, PM, Nevens, F, Kowdley, KV, Thorburn, D, Mason, AL, Trivedi, PJ, Lindor, KD, Bruns, T, Dalekos, GN, Gatselis, NK, Verhelst, X, Janssen, HL, Hansen, BE, Gulamhusein, A, Grp, GPS, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Gastroenterology & Hepatology, Murillo Perez, C, Hirschfield, G, Corpechot, C, Floreani, A, Mayo, M, van der Meer, A, Ponsioen, C, Lammers, W, Pares, A, Invernizzi, P, Carbone, M, Maria Battezzati, P, Nevens, F, Kowdley, K, Thorburn, D, Mason, A, Trivedi, P, Lindor, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Janssen, H, Hansen, B, and Gulamhusein, A

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Fibrosi, Biopsy, Context (language use), risk stratification, Chronic liver disease, Gastroenterology, Severity of Illness Index, Biomarkers, Pharmacological, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, MED/12 - GASTROENTEROLOGIA, Fibrosis, Predictive Value of Tests, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Primary Biliary Cholangiti, Stage (cooking), Hepatology, medicine.diagnostic_test, business.industry, Liver Cirrhosis, Biliary, Hazard ratio, Ursodeoxycholic Acid, Middle Aged, medicine.disease, Prognosis, Treatment Outcome, Liver, Liver biopsy, Disease Progression, 030211 gastroenterology & hepatology, Female, business, Liver function tests
Abstract

Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long‐term outcomes in the context of biochemical risk stratification Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris‐II criteria), as well as non‐invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB‐4), for transplant‐free survival was assessed with Cox proportional‐hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fi‐ brosis (stage 3/4) was an independent predictor of survival in addition to non‐invasive measures offibrosis with the hazard ratios ranging from 1.59 to 2.73 (P < .001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treat‐ ment response, with a 10‐year survival of 76.0%‐86.6% compared to 94.5%‐95.1% depending on the treatment response criteria used. Poor correlations were observed between non‐invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochem‐ ical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.

Published
2019

23. Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Author

Angela C. Cheung, Kris V. Kowdley, Marlyn J. Mayo, Albert Parés, Konstantinos N. Lazaridis, Ana Lleo, Aliya Gulamhusein, Keith D. Lindor, George N. Dalekos, Tony Bruns, Pietro Invernizzi, Annarosa Floreani, Harry L.A. Janssen, Xavier Verhelst, Willem J Lammers, Carla F. Murillo Perez, Frederik Nevens, Pier Maria Battezzati, Cyriel Y. Ponsioen, Henk R. van Buuren, Christophe Corpechot, Gideon M. Hirschfield, Marco Carbone, Douglas Thorburn, Bettina E. Hansen, Nikolaos K. Gatselis, Raoul Poupon, Andrew Mason, Palak J. Trivedi, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Gastroenterology & Hepatology, Cheung, A, Lammers, W, Murillo Perez, C, van Buuren, H, Gulamhusein, A, Trivedi, P, Lazaridis, K, Ponsioen, C, Floreani, A, Hirschfield, G, Corpechot, C, Mayo, M, Invernizzi, P, Battezzati, P, Parés, A, Nevens, F, Thorburn, D, Mason, A, Carbone, M, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Lindor, K, Lleo, A, Poupon, R, Janssen, H, and Hansen, B

Subjects
Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Cholangitis, Cholestatic Liver Disease, Mortality, Risk stratification, Stratified Medicine, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Interquartile range, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Longitudinal Studies, Aged, Retrospective Studies, Hepatology, Proportional hazards model, business.industry, Hazard ratio, Ursodeoxycholic Acid, Gastroenterology, Age Factors, Retrospective cohort study, Odds ratio, Middle Aged, Ursodeoxycholic acid, Liver Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. METHODS: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. RESULTS: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P

Published
2019

24. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history

Author

Kris V. Kowdley, George N. Dalekos, Pietro Invernizzi, Carla F. Murillo Perez, Gideon M. Hirschfield, Frederik Nevens, Douglas Thorburn, Marco Carbone, Xavier Verhelst, Cyriel Y. Ponsioen, Christophe Corpechot, Willem J Lammers, Aliya Gulamhusein, Jorn C Goet, Harry L.A. Janssen, Tony Bruns, Palak J. Trivedi, Annarosa Floreani, Pier Maria Battezzati, Kalliopi Zachou, Albert Parés, Marlyn J. Mayo, Henk R. van Buuren, Nicholas F. LaRusso, Bettina E. Hansen, Keith D. Lindor, Raoul Poupon, Andrew Mason, Gastroenterology & Hepatology, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Murillo Perez, C, Goet, J, Lammers, W, Gulamhusein, A, van Buuren, H, Ponsioen, C, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Thorburn, D, Hirschfield, G, Larusso, N, Lindor, K, Zachou, K, Poupon, R, Trivedi, P, Verhelst, X, Janssen, H, and Hansen, B

Subjects
Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Databases, Factual, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, Retrospective Studie, Internal medicine, medicine, Humans, Decompensation, diagnosis year, Cholagogues and Choleretic, Survival analysis, Aged, Retrospective Studies, Hepatology, medicine.diagnostic_test, Liver Function Test, business.industry, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Autoimmune liver disease, age at diagnosis, disease severity, epidemiology, Retrospective cohort study, Middle Aged, Survival Analysis, Ursodeoxycholic acid, Europe, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, North America, 030211 gastroenterology & hepatology, Female, Survival Analysi, Liver function, Liver function tests, business, Human, medicine.drug
Abstract

Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9 ± 10.1 years in the 1970s to 57.0 ± 12.1 years from 2010 onward (P < 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; P < 0.001). Conclusion: In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. (Hepatology 2018;67:1920-1930).

Published
2018
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25. Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival.

Author

Murillo Perez CF, Ioannou S, Hassanally I, Trivedi PJ, Corpechot C, van der Meer AJ, Lammers WJ, Battezzati PM, Lindor KD, Nevens F, Kowdley KV, Bruns T, Cazzagon N, Floreani A, Mason AL, Gulamhusein A, Ponsioen CY, Carbone M, Lleo A, Mayo MJ, Dalekos GN, Gatselis NK, Thorburn D, Verhelst X, Parés A, Londoño MC, Janssen HLA, Invernizzi P, Vuppalanchi R, Hirschfield GM, Hansen BE, and Levy C

Subjects
Humans, Female, Middle Aged, Male, Alkaline Phosphatase, Cholagogues and Choleretics therapeutic use, Bilirubin, Ursodeoxycholic Acid therapeutic use, Liver Cirrhosis, Biliary diagnosis, Liver Cirrhosis, Biliary drug therapy
Abstract

Background and Aims: Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response., Methods: UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected., Results: For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82-1.33) vs. 2.37 × ULN (1.72-3.69) at six months (p < .001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early., Conclusions: We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2023
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