Search

Your search keyword '"Corpechot, C"' showing total 374 results
Start Over Author "Corpechot, C"
374 results on '"Corpechot, C"'

3. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Author

Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., Carrat F., Corpechot, C, Lemoinne, S, Soret, P, Hansen, B, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Pares, A, Olivas, I, Eaton, J, Osman, K, Schramm, C, Sebode, M, Lohse, A, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Floreani, A, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Sobenko, N, Villamil, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, Van Der Meer, A, De Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Bruns, T, Grosse, K, Wetten, A, Dyson, J, Jones, D, Dumortier, J, Pageaux, G, De Ledinghen, V, Chazouilleres, O, Carrat, F, Corpechot C., Lemoinne S., Soret P. -A., Hansen B., Hirschfield G., Gulamhusein A., Montano-Loza A. J., Lytvyak E., Pares A., Olivas I., Eaton J. E., Osman K. T., Schramm C., Sebode M., Lohse A. W., Dalekos G., Gatselis N., Nevens F., Cazzagon N., Zago A., Russo F. P., Floreani A., Abbas N., Trivedi P., Thorburn D., Saffioti F., Barkai L., Roccarina D., Calvaruso V., Fichera A., Delamarre A., Sobenko N., Villamil A. M., Medina-Morales E., Bonder A., Patwardhan V., Rigamonti C., Carbone M., Invernizzi P., Cristoferi L., Van Der Meer A., De Veer R., Zigmond E., Yehezkel E., Kremer A. E., Deibel A., Bruns T., Grosse K., Wetten A., Dyson J. K., Jones D., Dumortier J., Pageaux G. -P., De Ledinghen V., Chazouilleres O., and Carrat F.

Abstract

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Published
2024

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

Author

Murilloperez, C, Ioannou, S, Hassanally, I, Trivedi, P, Corpechot, C, van der Meer, A, Lammers, W, Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Londono, M, Janssen, H, Invernizzi, P, Vuppalanchi, R, Hirschfield, G, Hansen, B, Levy, C, MurilloPerez C. F., Ioannou S., Hassanally I., Trivedi P. J., Corpechot C., van der Meer A. J., Lammers W. J., Battezzati P. M., Lindor K. D., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., 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., Londono M. -C., Janssen H. L. A., Invernizzi P., Vuppalanchi R., Hirschfield G. M., Hansen B. E., Levy C., Murilloperez, C, Ioannou, S, Hassanally, I, Trivedi, P, Corpechot, C, van der Meer, A, Lammers, W, Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Londono, M, Janssen, H, Invernizzi, P, Vuppalanchi, R, Hirschfield, G, Hansen, B, Levy, C, MurilloPerez C. F., Ioannou S., Hassanally I., Trivedi P. J., Corpechot C., van der Meer A. J., Lammers W. J., Battezzati P. M., Lindor K. D., Nevens F., Kowdley K. V., Bruns T., Cazzagon N., Floreani A., 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., Londono M. -C., Janssen H. L. A., Invernizzi P., Vuppalanchi R., Hirschfield G. M., Hansen B. E., and Levy C.

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.

Published
2023

5. 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

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, 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

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. Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis

Author

Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, Corpechot, C, Soret P. -A., Lam L., Carrat F., Smets L., Berg T., Carbone M., Invernizzi P., Leroy V., Trivedi P., Cazzagon N., Weiler-Normann C., Alric L., Rosa-Hezode I., Heurgue A., Cervoni J. -P., Dumortier J., Potier P., Roux O., Silvain C., Bureau C., Anty R., Larrey D., Levy C., Pares A., Schramm C., Nevens F., Chazouilleres O., Corpechot C., Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, Corpechot, C, Soret P. -A., Lam L., Carrat F., Smets L., Berg T., Carbone M., Invernizzi P., Leroy V., Trivedi P., Cazzagon N., Weiler-Normann C., Alric L., Rosa-Hezode I., Heurgue A., Cervoni J. -P., Dumortier J., Potier P., Roux O., Silvain C., Bureau C., Anty R., Larrey D., Levy C., Pares A., Schramm C., Nevens F., Chazouilleres O., and Corpechot C.

Abstract

Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC. Methods: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model. Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group. Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.

Published
2021

10. The genetic architecture of primary biliary cholangitis

Author

Gerussi, A, Carbone, M, Corpechot, C, Schramm, C, Asselta, R, Invernizzi, P, Gerussi A., Carbone M., Corpechot C., Schramm C., Asselta R., Invernizzi P., Gerussi, A, Carbone, M, Corpechot, C, Schramm, C, Asselta, R, Invernizzi, P, Gerussi A., Carbone M., Corpechot C., Schramm C., Asselta R., and Invernizzi P.

Abstract

Primary biliary cholangitis (PBC) is a rare autoimmune disease of the liver affecting the small bile ducts. From a genetic point of view, PBC is a complex trait and several genetic and environmental factors have been called in action to explain its etiopathogenesis. Similarly to other complex traits, PBC has benefited from the introduction of genome-wide association studies (GWAS), which identified many variants predisposing or protecting toward the development of the disease. While a progressive endeavour toward the characterization of candidate loci and downstream pathways is currently ongoing, there is still a relatively large portion of heritability of PBC to be revealed. In addition, genetic variation behind progression of the disease and therapeutic response are mostly to be investigated yet. This review outlines the state-of-the-art regarding the genetic architecture of PBC and provides some hints for future investigations, focusing on the study of gene-gene interactions, the application of whole-genome sequencing techniques, and the investigation of X chromosome that can be helpful to cover the missing heritability gap in PBC.

Published
2021

11. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis

Author

Harms, M, De Veer, R, Lammers, W, Corpechot, C, Thorburn, D, Janssen, H, Lindor, K, Trivedi, P, Hirschfield, G, Pares, A, Floreani, A, Mayo, M, Invernizzi, P, Battezzati, P, Nevens, F, Ponsioen, C, Mason, A, Kowdley, K, Hansen, B, Buuren, H, Van Der Meer, A, Harms M. H., De Veer R. C., Lammers W. J., Corpechot C., Thorburn D., Janssen H. L. A., Lindor K. D., Trivedi P. J., Hirschfield G. M., Pares A., Floreani A., Mayo M. J., Invernizzi P., Battezzati P. M., Nevens F., Ponsioen C. Y., Mason A. L., Kowdley K. V., Hansen B. E., Buuren H. R. V., Van Der Meer A. J., Harms, M, De Veer, R, Lammers, W, Corpechot, C, Thorburn, D, Janssen, H, Lindor, K, Trivedi, P, Hirschfield, G, Pares, A, Floreani, A, Mayo, M, Invernizzi, P, Battezzati, P, Nevens, F, Ponsioen, C, Mason, A, Kowdley, K, Hansen, B, Buuren, H, Van Der Meer, A, Harms M. H., De Veer R. C., Lammers W. J., Corpechot C., Thorburn D., Janssen H. L. A., Lindor K. D., Trivedi P. J., Hirschfield G. M., Pares A., Floreani A., Mayo M. J., Invernizzi P., Battezzati P. M., Nevens F., Ponsioen C. Y., Mason A. L., Kowdley K. V., Hansen B. E., Buuren H. R. V., and Van Der Meer A. J.

Abstract

Objective The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC. Methods The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database. Results We included 3902 patients with a median follow-up of 7.8 (4.1-12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT 5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT 5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2-4× ULN) and high ALP (>4× ULN), the NNT 5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively. Conclusion The absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.

Published
2020

12. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis

Author

Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Corpechot C., Chazouilleres O., Belnou P., Montano-Loza A. J., Mason A., Ebadi M., Eurich D., Chopra S., Jacob D., Schramm C., Sterneck M., Bruns T., Reuken P., Rauchfuss F., Roccarina D., Thorburn D., Gerussi A., Trivedi P., Hirschfield G., McDowell P., Nevens F., Boillot O., Bosch A., Giostra E., Conti F., Poupon R., Pares A., Reig A., Donato M. F., Malinverno F., Floreani A., Russo F. P., Cazzagon N., Verhelst X., Goet J., Harms M., van Buuren H., Hansen B., Carrat F., Dumortier J., Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Corpechot C., Chazouilleres O., Belnou P., Montano-Loza A. J., Mason A., Ebadi M., Eurich D., Chopra S., Jacob D., Schramm C., Sterneck M., Bruns T., Reuken P., Rauchfuss F., Roccarina D., Thorburn D., Gerussi A., Trivedi P., Hirschfield G., McDowell P., Nevens F., Boillot O., Bosch A., Giostra E., Conti F., Poupon R., Pares A., Reig A., Donato M. F., Malinverno F., Floreani A., Russo F. P., Cazzagon N., Verhelst X., Goet J., Harms M., van Buuren H., Hansen B., Carrat F., and Dumortier J.

Abstract

Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13–0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22–0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49–0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28–3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death. Conclusions: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality. Lay summary: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We perform

Published
2020

13. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

Author

Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolaos, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Douglas, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vicenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vilas, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, and de Lédinghen, Victor

Abstract

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. Methods: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. Results: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026–1.054) and 1.042 (1.029–1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79–0.87) and 0.92 (0.89–0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. Conclusions: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. Lay summary: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses

Published
2022

14. Machine learning in primary biliary cholangitis: A novel approach for risk stratification

Author

Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Vespasiani‐gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Gerussi, Alessio, Verda, Damiano, Bernasconi, Davide Paolo, Carbone, Marco, Komori, Atsumasa, Abe, Masanori, Inao, Mie, Namisaki, Tadashi, Mochida, Satoshi, Yoshiji, Hitoshi, Hirschfield, Gideon, Lindor, Keith, Pares, Albert, Corpechot, Christophe, Cazzagon, Nora, Floreani, Annarosa, Marzioni, Marco, Alvaro, Domenico, Vespasiani‐Gentilucci, Umberto, Cristoferi, Laura, Valsecchi, Maria Grazia, Muselli, Marco, Hansen, Bettina E., Tanaka, Atsushi, Invernizzi, Pietro, Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Vespasiani‐gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Gerussi, Alessio, Verda, Damiano, Bernasconi, Davide Paolo, Carbone, Marco, Komori, Atsumasa, Abe, Masanori, Inao, Mie, Namisaki, Tadashi, Mochida, Satoshi, Yoshiji, Hitoshi, Hirschfield, Gideon, Lindor, Keith, Pares, Albert, Corpechot, Christophe, Cazzagon, Nora, Floreani, Annarosa, Marzioni, Marco, Alvaro, Domenico, Vespasiani‐Gentilucci, Umberto, Cristoferi, Laura, Valsecchi, Maria Grazia, Muselli, Marco, Hansen, Bettina E., Tanaka, Atsushi, and Invernizzi, Pietro

Abstract

Background & Aims: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC). Methods: ML was applied to an international dataset of PBC patients. The dataset was split into a derivation cohort (training set) and a validation cohort (validation set), and key clinical features were analysed. The outcome was a composite of liver-related death or liver transplantation. ML and standard survival analysis were performed. Results: The training set was composed of 11,819 subjects, while the validation set was composed of 1,069 subjects. ML identified four clusters of patients characterized by different phenotypes and long-term prognosis. Cluster 1 (n = 3566) included patients with excellent prognosis, whereas Cluster 2 (n = 3966) consisted of individuals at worse prognosis differing from Cluster 1 only for albumin levels around the limit of normal. Cluster 3 (n = 2379) included young patients with florid cholestasis and Cluster 4 (n = 1908) comprised advanced cases. Further sub-analyses on the dynamics of albumin within the normal range revealed that ursodeoxycholic acid-induced increase of albumin >1.2 x lower limit of normal (LLN) is associated with improved transplant-free survival. Conclusions: Unsupervised ML identified four novel groups of PBC patients with different phenotypes and prognosis and highlighted subtle variations of albumin within the normal range. Therapy-induced increase of albumin >1.2 x LLN should be considered a treatment goal.

Published
2022

17. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis

Author

Harms, M, van Buuren, H, Corpechot, C, Thorburn, D, Janssen, H, Lindor, K, Hirschfield, G, Pares, A, Floreani, A, Mayo, M, Invernizzi, P, Battezzati, P, Nevens, F, Ponsioen, C, Mason, A, Kowdley, K, Lammers, W, Hansen, B, van der Meer, A, Harms M. H., van Buuren H. R., Corpechot C., Thorburn D., Janssen H. L. A., Lindor K. D., Hirschfield G. M., Pares A., Floreani A., Mayo M. J., Invernizzi P., Battezzati P. M., Nevens F., Ponsioen C. Y., Mason A. L., Kowdley K. V., Lammers W. J., Hansen B. E., van der Meer A. J., Harms, M, van Buuren, H, Corpechot, C, Thorburn, D, Janssen, H, Lindor, K, Hirschfield, G, Pares, A, Floreani, A, Mayo, M, Invernizzi, P, Battezzati, P, Nevens, F, Ponsioen, C, Mason, A, Kowdley, K, Lammers, W, Hansen, B, van der Meer, A, Harms M. H., van Buuren H. R., Corpechot C., Thorburn D., Janssen H. L. A., Lindor K. D., Hirschfield G. M., Pares A., Floreani A., Mayo M. J., Invernizzi P., Battezzati P. M., Nevens F., Ponsioen C. Y., Mason A. L., Kowdley K. V., Lammers W. J., Hansen B. E., and van der Meer A. J.

Abstract

Background & Aims: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC. Methods: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW). Results: In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1–12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1–81.2) among UDCA-treated patients and 60.7% (95% CI 58.2–63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40–0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45–0.69; p <0.001). Conclusion: The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC. Lay summary: In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated

Published
2019

18. 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

20. Measurement of Gamma Glutamyl Transferase to Determine Risk of Liver Transplantation or Death in Patients With Primary Biliary Cholangitis

Author

Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Verhelst, X, Kowdley, K, van der Meer, A, Niro, G, Beretta-Piccoli, B, Marzioni, M, Belli, L, Marra, F, Valsecchi, M, Lindor, K, Invernizzi, P, Hansen, B, Carbone, M, Gerussi, Alessio, Bernasconi, Davide Paolo, O'Donnell, Sarah Elisabeth, Lammers, Willem J, Buuren, Henk Van, Hirschfield, Gideon, Janssen, Harry, Corpechot, Christophe, Reig, Anna, Pares, Albert, Battezzati, Pier Maria, Zuin, Massimo Giovanni, Cazzagon, Nora, Floreani, Annarosa, Nevens, Frederik, Gatselis, Nikolaos, Dalekos, George, Mayo, Marlyn J, Thorburn, Douglas, Bruns, Tony, Mason, Andrew L, Verhelst, Xavier, Kowdley, Kris, van der Meer, Adriaan, Niro, Grazia Anna, Beretta-Piccoli, Benedetta Terziroli, Marzioni, Marco, Belli, Luca Saverio, Marra, Fabio, Valsecchi, Maria Grazia, Lindor, Keith D, Invernizzi, Pietro, Hansen, Bettina E, Carbone, Marco, Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Verhelst, X, Kowdley, K, van der Meer, A, Niro, G, Beretta-Piccoli, B, Marzioni, M, Belli, L, Marra, F, Valsecchi, M, Lindor, K, Invernizzi, P, Hansen, B, Carbone, M, Gerussi, Alessio, Bernasconi, Davide Paolo, O'Donnell, Sarah Elisabeth, Lammers, Willem J, Buuren, Henk Van, Hirschfield, Gideon, Janssen, Harry, Corpechot, Christophe, Reig, Anna, Pares, Albert, Battezzati, Pier Maria, Zuin, Massimo Giovanni, Cazzagon, Nora, Floreani, Annarosa, Nevens, Frederik, Gatselis, Nikolaos, Dalekos, George, Mayo, Marlyn J, Thorburn, Douglas, Bruns, Tony, Mason, Andrew L, Verhelst, Xavier, Kowdley, Kris, van der Meer, Adriaan, Niro, Grazia Anna, Beretta-Piccoli, Benedetta Terziroli, Marzioni, Marco, Belli, Luca Saverio, Marra, Fabio, Valsecchi, Maria Grazia, Lindor, Keith D, Invernizzi, Pietro, Hansen, Bettina E, and Carbone, Marco

Abstract

Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC). Methods: We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death. Results: Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r=0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum level of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P<.05). Including information on level of GGT increased the prognostic value of the Globe score. Conclusion: Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatm

Published
2021

21. Cluster analysis reveals the prognostic role of serum albumin within the normal range in patients with primary biliary cholangitis

Author

Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Lindor, KD, Gentilucci, UV, Valsecchi, MG, Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Lindor, KD, Gentilucci, UV, and Valsecchi, MG

Published
2021

22. Clustering Reveals the Prognostic Role of Serum Albumin Values Within the Normal Range in Patients with Primary Biliary Cholangitis

Author

Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Vespasiani-Gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Bernasconi, DP, Valsecchi, MG, Hansen, BE, Gerussi, A, Verda, D, Bernasconi, D, Carbone, M, Komori, A, Abe, M, Inao, M, Namisaki, T, Mochida, S, Yoshiji, H, Hirschfield, G, Lindor, K, Pares, A, Corpechot, C, Cazzagon, N, Floreani, A, Marzioni, M, Alvaro, D, Vespasiani-Gentilucci, U, Cristoferi, L, Valsecchi, M, Muselli, M, Hansen, B, Tanaka, A, Invernizzi, P, Bernasconi, DP, Valsecchi, MG, and Hansen, BE

Published
2021

23. OC-030 Effective Stratification of Hepatocellular Carcinoma Risk in Primary Biliary Cirrhosis: Results of a Multi-centre International Study

Author

Trivedi, PJ, Lammers, W, van Buuren, H, Janssen, H, Invernizzi, P, Battezzati, PM, Floreani, A, Pares, A, Ponsioen, C, Corpechot, C, Poupon, R, Mayo, M, Talwalkar, J, Burroughs, A, Nevens, F, Mason, A, Bruns, T, Li, K-K, Kowdley, K, Kumagi, T, Cheung, A, Lleo, A, Cazagon, N, Franceschet, I, Caballería, L, Boonstra, K, de Vries, E, Imam, M, Pieri, G, Kanwar, P, Lindor, K, Hansen, B, and Hirschfield, G

Published
2014
Full Text
View/download PDF

24. 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

25. 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

26. Factors Associated With Progression and Outcomes of Early Stage Primary Biliary Cholangitis

Author

Gatselis, N, Goet, J, Zachou, K, Lammers, W, Janssen, H, Hirschfield, G, Corpechot, C, Lindor, K, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Lygoura, V, Nevens, F, Mason, A, Kowdley, K, Ponsioen, C, Bruns, T, Thorburn, D, Verhelst, X, Harms, M, van Buuren, H, Hansen, B, Dalekos, G, Gatselis, Nikolaos K, Goet, Jorn C, Zachou, Kalliopi, Lammers, Willem J, Janssen, Harry L A, Hirschfield, Gideon, Corpechot, Christophe, Lindor, Keith D, Invernizzi, Pietro, Mayo, Marlyn J, Battezzati, Pier Maria, Floreani, Annarosa, Pares, Albert, Lygoura, Vasiliki, Nevens, Frederik, Mason, Andrew L, Kowdley, Kris V, Ponsioen, Cyriel Y, Bruns, Tony, Thorburn, Douglas, Verhelst, Xavier, Harms, Maren H, van Buuren, Henk R, Hansen, Bettina E, Dalekos, George N, Gatselis, N, Goet, J, Zachou, K, Lammers, W, Janssen, H, Hirschfield, G, Corpechot, C, Lindor, K, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Lygoura, V, Nevens, F, Mason, A, Kowdley, K, Ponsioen, C, Bruns, T, Thorburn, D, Verhelst, X, Harms, M, van Buuren, H, Hansen, B, Dalekos, G, Gatselis, Nikolaos K, Goet, Jorn C, Zachou, Kalliopi, Lammers, Willem J, Janssen, Harry L A, Hirschfield, Gideon, Corpechot, Christophe, Lindor, Keith D, Invernizzi, Pietro, Mayo, Marlyn J, Battezzati, Pier Maria, Floreani, Annarosa, Pares, Albert, Lygoura, Vasiliki, Nevens, Frederik, Mason, Andrew L, Kowdley, Kris V, Ponsioen, Cyriel Y, Bruns, Tony, Thorburn, Douglas, Verhelst, Xavier, Harms, Maren H, van Buuren, Henk R, Hansen, Bettina E, and Dalekos, George N

Abstract

Background & Aims: Patients usually receive a diagnosis of primary biliary cholangitis (PBC) at an early stage, based on biochemical analyses. We investigated the proportion of patients who progress to moderate or advanced PBC and factors associated with progression and patient survival. Methods: We obtained data from 1615 patients (mean age, 55.4 y) with early stage PBC (based on their normal levels of albumin and bilirubin), collected at the time of initial evaluation or treatment, from the Global PBC Study Group database (comprising patients at 19 liver centers in North American and European countries). We collected data from health care evaluations on progression to moderate PBC (abnormal level of bilirubin or albumin) or advanced-stage PBC (abnormal level of both). The median follow-up time was 7.9 years. The composite end point was decompensation, hepatocellular carcinoma, liver transplantation, or death. Results: Of the 1615 patients identified with early stage PBC, 904 developed moderate PBC and 201 developed advanced disease over the study period. The proportions of patients who transitioned to moderate PBC at 1, 3, and 5 years were 12.9%, 30.2%, and 45.8%. The proportions of these patients who then transitioned to advanced PBC at 1, 3, and 5 years later were 3.4%, 12.5%, and 16.0%, respectively. During the follow-up period, 236 patients had a clinical event. The proportions of patients with moderate PBC and event-free survival were 97.9%, 95.1%, and 91.5% at 1, 3, and 5 years, respectively, and the proportions of patients with advanced PBC and event-free survival were 90.6%, 71.2%, and 58.3% at 1, 3, and 5 years later, respectively. Variables associated with transition from early to moderate PBC included baseline levels of bilirubin, albumin, and alkaline phosphatase; aspartate to alanine aminotransferase ratio; platelet count; and treatment with ursodeoxycholic acid. Transitions from early to moderate PBC and from moderate to advanced PBC were associated

Published
2020

27. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis

Author

Harms, Maren, de Veer, Rozanne, Lammers, Wim, Corpechot, C, Thorburn, D, Janssen, HL, Lindor, KD, Trivedi, PJ, Hirschfield, GM, Pares, A, Floreani, A, Mayo, MJ, Invernizzi, P, Battezzati, PM, Nevens, F, Ponsioen, CY, Mason, AL, Kowdley, KV, Hansen, BE, van Buuren, Henk, van der Meer, Adriaan, Harms, Maren, de Veer, Rozanne, Lammers, Wim, Corpechot, C, Thorburn, D, Janssen, HL, Lindor, KD, Trivedi, PJ, Hirschfield, GM, Pares, A, Floreani, A, Mayo, MJ, Invernizzi, P, Battezzati, PM, Nevens, F, Ponsioen, CY, Mason, AL, Kowdley, KV, Hansen, BE, van Buuren, Henk, and van der Meer, Adriaan

Published
2020

28. Serum gamma-glutamyltransferase is a prognostic biomarker in primary biliary cholangitis and improves risk stratification based on alkaline phosphatase

Author

Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Van Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Xavier, V, Kowdley, K, Invernizzi, P, Hansen, B, Carbone, M, O'donnell, SE, Lammers, WJ, Battezzati, PM, Zuin, MG, Mayo, MJ, Mason, AL, Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Van Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Xavier, V, Kowdley, K, Invernizzi, P, Hansen, B, Carbone, M, O'donnell, SE, Lammers, WJ, Battezzati, PM, Zuin, MG, Mayo, MJ, and Mason, AL

Published
2020

29. The impact of geographical region on outcomes of patients with primary biliary cholangitis from western Europe

Author

Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van der Meer, A, Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Mayo, M, Lleo, A, Dalekos, G, Gatselis, N, Thorburn, D, Xavier, V, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, Lammers, W, Perez, CFM, Battezzati, PM, Lindor, KD, Kowdley, KV, Mason, AL, Mayo, MJ, Lammers, WJ, Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van der Meer, A, Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Mayo, M, Lleo, A, Dalekos, G, Gatselis, N, Thorburn, D, Xavier, V, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, Lammers, W, Perez, CFM, Battezzati, PM, Lindor, KD, Kowdley, KV, Mason, AL, Mayo, MJ, and Lammers, WJ

Published
2020

30. Serum gamma-glutamyltransferase is a prognostic biomarker in primary biliary cholangitis and improves risk stratification based on the alkaline phosphatase

Author

Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Van Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Xavier, V, Kowdley, K, Invernizzi, P, Hansen, B, Carbone, M, O'Donnell, SE, Lammers, WJ, Battezzati, PM, Zuin, MG, Mayo, MJ, Mason, AL, Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Van Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Xavier, V, Kowdley, K, Invernizzi, P, Hansen, B, Carbone, M, O'Donnell, SE, Lammers, WJ, Battezzati, PM, Zuin, MG, Mayo, MJ, and Mason, AL

Published
2020

31. Clustering Reveals the Prognostic Role of Serum Albumin Values Within the Normal Range in Patients with Primary Biliary Cholangitis

Author

Gerussi, A., primary, Verda, D., additional, Bernasconi, D.P., additional, Carbone, M., additional, Komori, A., additional, Abe, M., additional, Inao, M., additional, Namisaki, T., additional, Mochida, S., additional, Yoshiji, H., additional, Hirschfield, G., additional, Lindor, K., additional, Pares, A., additional, Corpechot, C., additional, Cazzagon, N., additional, Floreani, A., additional, Marzioni, M., additional, Alvaro, D., additional, Vespasiani-Gentilucci, U., additional, Cristoferi, L., additional, Valsecchi, M.G., additional, Muselli, M., additional, Study Group, the Japan PBC, additional, Study Group, the Global PBC, additional, study Group, the Italian PBC, additional, Hansen, B.E., additional, Tanaka, A., additional, and Invernizzi, P., additional

Published
2021
Full Text
View/download PDF

34. THU0051 LOW-DOSE INTERLEUKIN-2 SELECTIVELY EXPAND AND ACTIVATE REGULATORY T CELLS ACROSS 13 AUTOIMMUNE DISEASES.

Author

Rosenzwajg, M., primary, Lorenzon, R., additional, Cacoub, P., additional, Pitoiset, F., additional, Aractingi, S., additional, Banneville, B., additional, Beaugerie, L., additional, Berenbaum, F., additional, Champey, J., additional, Chazouilleres, O., additional, Corpechot, C., additional, Fautrel, B., additional, Mekinian, A., additional, Regnier, E., additional, Saadoun, D., additional, Salem, J. E., additional, Sellam, J., additional, Seksik, P., additional, and Klatzmann, D., additional

Published
2020
Full Text
View/download PDF

35. Serum gamma-glutamyltransferase is a prognostic biomarker in primary biliary cholangitis and improves risk stratification based on alkaline phosphatase

Author

Gerussi, A., primary, Bernasconi, D., additional, O’donnell, S.E., additional, Lammers, W.J., additional, Van Buuren, H., additional, Hirschfield, G., additional, Janssen, H., additional, Corpechot, C., additional, Reig, A., additional, Pares, A., additional, Battezzati, P.M., additional, Zuin, M.G., additional, Cazzagon, N., additional, Floreani, A., additional, Nevens, F., additional, Gatselis, N., additional, Dalekos, G., additional, Mayo, M.J., additional, Thorburn, D., additional, Bruns, T., additional, Mason, A.L., additional, Xavier, V., additional, Kowdley, K., additional, Invernizzi, P., additional, Hansen, B., additional, and Carbone, M., additional

Published
2020
Full Text
View/download PDF

36. Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals

Author

Bazerbachi, F. Haffar, S. Wang, Z. Cabezas, J. Arias-Loste, M.T. Crespo, J. Darwish-Murad, S. Ikram, M.A. Olynyk, J.K. Gan, E. Petta, S. Berzuini, A. Prati, D. de Lédinghen, V. Wong, V.W. Del Poggio, P. Chávez-Tapia, N.C. Chen, Y.-P. Cheng, P.-N. Yuen, M.-F. Das, K. Chowdhury, A. Caballeria, L. Fabrellas, N. Ginès, P. Kumar, M. Sarin, S.K. Conti, F. Andreone, P. Sirli, R. Cortez-Pinto, H. Carvalhana, S. Sugihara, T. Kim, S.U. Parikh, P. Chayama, K. Corpechot, C. Kim, K.M. Papatheodoridis, G. Alsebaey, A. Kamath, P.S. Murad, M.H. Watt, K.D.

Abstract

Background & Aims: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. Methods: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index

Published
2019

38. Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis

Author

Harms, M.H. (Maren), De Veer, R.C. (Rozanne C.), Lammers, W.J. (Wim), Corpechot, C. (Christophe), Thorburn, D. (Douglas), Janssen, H.L.A. (Harry), Lindor, K.D. (Keith), Trivedi, P.J. (Palak J.), Hirschfield, G.M. (Gideon), Parés, A. (Albert), Floreani, A. (Annarosa), Mayo, M.J. (Marlyn J.), Invernizzi, P. (Pietro), Battezzati, P.M. (Pier Maria), Nevens, F. (Frederik), Ponsioen, C.Y. (Cyril), Mason, A.L. (Andrew L.), Kowdley, K.V. (Kris), Hansen, B.E. (Bettina), Buuren, H.R. (Henk) van, Meer, A.J.P. (Adriaan) van der, Harms, M.H. (Maren), De Veer, R.C. (Rozanne C.), Lammers, W.J. (Wim), Corpechot, C. (Christophe), Thorburn, D. (Douglas), Janssen, H.L.A. (Harry), Lindor, K.D. (Keith), Trivedi, P.J. (Palak J.), Hirschfield, G.M. (Gideon), Parés, A. (Albert), Floreani, A. (Annarosa), Mayo, M.J. (Marlyn J.), Invernizzi, P. (Pietro), Battezzati, P.M. (Pier Maria), Nevens, F. (Frederik), Ponsioen, C.Y. (Cyril), Mason, A.L. (Andrew L.), Kowdley, K.V. (Kris), Hansen, B.E. (Bettina), Buuren, H.R. (Henk) van, and Meer, A.J.P. (Adriaan) van der

Abstract

Objective: The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC. Methods: The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database. Results: We included 3902 patients with a median follow-up of 7.8 (4.1-12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2-4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively. Conclusion: The absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.

Published
2019
Full Text
View/download PDF

39. 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

40. Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals

Author

Bazerbachi, F., Haffar, S., Wang, Z., Cabezas, J., Arias-Loste, M., Crespo, J., Darwish-Murad, S., Ikram, M., Olynyk, John, Gan, E., Petta, S., Berzuini, A., Prati, D., de Lédinghen, V., Wong, V., Del Poggio, P., Chávez-Tapia, N., Chen, Y., Cheng, P., Yuen, M., Das, K., Chowdhury, A., Caballeria, L., Fabrellas, N., Ginès, P., Kumar, M., Sarin, S., Conti, F., Andreone, P., Sirli, R., Cortez-Pinto, H., Carvalhana, S., Sugihara, T., Kim, S., Parikh, P., Chayama, K., Corpechot, C., Kim, K., Papatheodoridis, G., Alsebaey, A., Kamath, P., Murad, M., Watt, K., Bazerbachi, F., Haffar, S., Wang, Z., Cabezas, J., Arias-Loste, M., Crespo, J., Darwish-Murad, S., Ikram, M., Olynyk, John, Gan, E., Petta, S., Berzuini, A., Prati, D., de Lédinghen, V., Wong, V., Del Poggio, P., Chávez-Tapia, N., Chen, Y., Cheng, P., Yuen, M., Das, K., Chowdhury, A., Caballeria, L., Fabrellas, N., Ginès, P., Kumar, M., Sarin, S., Conti, F., Andreone, P., Sirli, R., Cortez-Pinto, H., Carvalhana, S., Sugihara, T., Kim, S., Parikh, P., Chayama, K., Corpechot, C., Kim, K., Papatheodoridis, G., Alsebaey, A., Kamath, P., Murad, M., and Watt, K.

Abstract

Background & Aims: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. Methods: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index =30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. Results: We established LSM ranges for healthy individuals measured with both probes—these did not change significantly in sensitivity analyses of individuals with platelets =150,000/mm3 and levels of alanine aminotransferase =33 IU/L in men or =25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased

Published
2019

41. Magnetic resonance risk score and liver stiffness by transient elastography have complementary prognostic values in patients with Primary Sclerosing Cholangitis

Author

Cazzagon, N., primary, Mouhadi, S. El, additional, Lemoinne, S., additional, Trivedi, P.J., additional, Gaouar, F., additional, Fankem, A.D. Kemgang, additional, Belkacem, K. Ben, additional, Floreani, A., additional, Hirschfield, G., additional, Chretien, Y., additional, Housset, C., additional, Motta, R., additional, Russo, F.P., additional, Chazouillères, O., additional, Arrivé, L., additional, and Corpechot, C., additional

Published
2019
Full Text
View/download PDF

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

Author

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

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.

Published
2018
Full Text
View/download PDF

43. 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

44. Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: Risk factors and time trends in incidence and outcome

Author

Harms, M, Lammers, W, Thorburn, D, Corpechot, C, Invernizzi, P, Janssen, H, Battezzati, P, Nevens, F, Lindor, K, Floreani, A, Ponsioen, C, Mayo, M, Dalekos, G, Bruns, T, Parés, A, Mason, A, Verhelst, X, Kowdley, K, Goet, J, Hirschfield, G, Hansen, B, Van Buuren, H, Harms, Maren H., Lammers, Willem J., Thorburn, Douglas, Corpechot, Christophe, Invernizzi, Pietro, Janssen, Harry L. A., Battezzati, Pier M., Nevens, Frederik, Lindor, Keith D., Floreani, Annarosa, Ponsioen, Cyriel Y., Mayo, Marlyn J., Dalekos, George N., Bruns, Tony, Parés, Albert, Mason, Andrew L., Verhelst, Xavier, Kowdley, Kris V., Goet, Jorn C., Hirschfield, Gideon M., Hansen, Bettina E., Van Buuren, Henk R., Harms, M, Lammers, W, Thorburn, D, Corpechot, C, Invernizzi, P, Janssen, H, Battezzati, P, Nevens, F, Lindor, K, Floreani, A, Ponsioen, C, Mayo, M, Dalekos, G, Bruns, T, Parés, A, Mason, A, Verhelst, X, Kowdley, K, Goet, J, Hirschfield, G, Hansen, B, Van Buuren, H, Harms, Maren H., Lammers, Willem J., Thorburn, Douglas, Corpechot, Christophe, Invernizzi, Pietro, Janssen, Harry L. A., Battezzati, Pier M., Nevens, Frederik, Lindor, Keith D., Floreani, Annarosa, Ponsioen, Cyriel Y., Mayo, Marlyn J., Dalekos, George N., Bruns, Tony, Parés, Albert, Mason, Andrew L., Verhelst, Xavier, Kowdley, Kris V., Goet, Jorn C., Hirschfield, Gideon M., Hansen, Bettina E., and Van Buuren, Henk R.

Abstract

Objectives: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. Methods: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. Results: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P<0.001), high aspartate aminotransferase to platelets ratio index (APRI; P<0.001) and biochemical non-response (P<0.001) were independently associated with future complications. Patients with both biochemical non-response and an APRI >0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. Conclusions: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.

Published
2018

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

Author

Murillo Perez, Fiorella, Goet, Jorn, Lammers, Wim, Gulamhusein, A, van Buuren, Henk, Ponsioen, CY, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, MJ, Battezzati, PM, Floreani, A, Pares, A, Nevens, F, Kowdley, KV, Bruns, T, Dalekos, GN, Thorburn, D, Hirschfield, G, LaRusso, NF, Lindor, KD, Zachou, K, Poupon, R, Trivedi, PJ, Verhelst, X, Janssen, HLA, Hansen, Bettina, Murillo Perez, Fiorella, Goet, Jorn, Lammers, Wim, Gulamhusein, A, van Buuren, Henk, Ponsioen, CY, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, MJ, Battezzati, PM, Floreani, A, Pares, A, Nevens, F, Kowdley, KV, Bruns, T, Dalekos, GN, Thorburn, D, Hirschfield, G, LaRusso, NF, Lindor, KD, Zachou, K, Poupon, R, Trivedi, PJ, Verhelst, X, Janssen, HLA, and Hansen, Bettina

Published
2018

46. Changes in serum bile acid levels associated with bezafibrate add-on therapy in patients with primary biliary cholangitis and inadequate biochemical response to ursodeoxycholic acid: results from the BEZURSO trial (NCT01654731)

Author

Corpechot, C., Chazouilleres, O., Humbert, L., Rousseau, A., Le Gruyer, A., Habersetzer, F., Philippe Mathurin, Goria, O., Potier, P., Anne, M., Silvain, C., Abergel, A., Debette-Gratien, M., Larrey, D. G., Roux, O., Bronowicki, J. P., Boursier, J., Ledinghen, V., Heurgue-Berlot, A., Nguyen-Khac, E., Zoulim, F., Ollivier-Hourmand, I., Zarski, J. P. H., Nkontchou, G., Gaouar, F., Simon, T., Poupon, R., Rainteau, D., CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Pôle Hépato-digestif, Les Hôpitaux Universitaires de Strasbourg (HUS), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional d'Orléans (CHRO), Unité d'Hépatologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Department of Digestive and Hepatobiliary Medecine, University Medical Hospital, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Méthodes Formelles pour la Bioinformatique (LS2N - équipe MéForBio), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital universitaire Robert Debré [Reims], Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Hépato-Gastroentérologie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Jean Verdier [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

68th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Washington, DC, OCT 20-24, 2017; International audience

Published
2017

48. Two simple magnetic resonance scores are able to predict survival in patients with Primary Sclerosing Cholangitis

Author

Cazzagon, N., primary, Lemoinne, S., additional, Mouhadi, S. El, additional, Trivedi, P., additional, Dohan, A., additional, Fankem, A. Kemgang, additional, Housset, C., additional, Chretien, Y., additional, Corpechot, C., additional, Hirschfield, G., additional, Floreani, A., additional, Motta, R., additional, Gallix, B., additional, Barkun, A., additional, Barkun, J., additional, Chazouilleres, O., additional, and Arrivé, L., additional

Published
2018
Full Text
View/download PDF

49. Histologic stage is a stronger predictor of transplant free survival than APRI and FIB-4 in patients with primary biliary cholangitis

Author

Gulamhusein, A., primary, Perez, C.F.M., additional, Van Buuren, H., additional, Corpechot, C., additional, Trivedi, P., additional, Carbone, M., additional, Pares, A., additional, Lammers, W.J., additional, Harms, M., additional, Floreani, A., additional, Lindor, K., additional, Ponsioen, C., additional, Invernizzi, P., additional, Mayo, M.J., additional, Battezzati, P.M., additional, Nevens, F., additional, Bruns, T., additional, Dalekos, G., additional, Thorburn, D., additional, Larusso, N., additional, Zachou, K., additional, Poupon, R., additional, Xavier, V., additional, Mason, A.L., additional, Kowdley, K.V., additional, Janssen, H., additional, Hirschfield, G., additional, and Hansen, B., additional

Published
2018
Full Text
View/download PDF

50. Ursodeoxycholic acid treatment is associated with prolonged transplant-free survival in primary biliary cholangitis – even in patients without biochemical improvements

Author

Harms, M., primary, Van Buuren, H., additional, Lammers, W.J., additional, Corpechot, C., additional, Thorburn, D., additional, Invernizzi, P., additional, Janssen, H., additional, Battezzati, P.M., additional, Nevens, F., additional, Lindor, K., additional, Floreani, A., additional, Ponsioen, C., additional, Mayo, M.J., additional, Pares, A., additional, Mason, A.L., additional, Kowdley, K.V., additional, Hirschfield, G., additional, Hansen, B., additional, and Van der Meer, A., additional

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results