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480 results on '"Hirschfield G."'

1. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Author: van Gerven, N., van Erpecum, K., Ouden, J den, Brouwer, J., Vrolijk, J., Gevers, T.J., Drenth, J., Guichelaar, M., Bouma, G., Schreuder, T.C.M.A., van der Wouden, E.J., Baak, L.C., Stadhouders, P., Klemt-Kropp, M., Verhagen, M., Bhalla, A., Kuijvenhoven, J., Almasio, P., Alvarez, F., Andrade, R., Arikan, C., Assis, D., Bardou-Jacquet, E., Biewenga, M., Cancado, E., Cazzagon, N., Chazouillères, O., Colloredo, G., Cuarterolo, M., Dalekos, G., Debray, D., Robles-Díaz, M., Dyson, J., Efe, C., Engel, B., Ferri, S., Fontana, R., Gatselis, N., Gerussi, A., Halilbasic, E., Halliday, N., Heneghan, M., Hirschfield, G., van Hoek, B., Hørby Jørgensen, M., Indolfini, G., Iorio, R., Invernizzi, P., Jeong, S., Jones, D., Kelly, D., Kerkar, N., Lacaille, F., Lammert, C., Leggett, B., Lenzi, M., Levy, C., Liberal, R., Lleo, A., Lohse, A., Lopez, S. Ines, de Martin, E., McLin, V., Mieli-Vergani, G., Milkiewicz, P., Mohan, N., Muratori, L., Nebbia, G., van Nieuwkerk, C., Oo, Y., Ortega, A., Páres, A., Pop, T., Pratt, D., Purnak, T., Ranucci, G., Rushbrook, S., Schramm, C., Stättermayer, A., Swain, M., Tanaka, A., Taubert, R., Terrabuio, D., Terziroli, B., Trauner, M., Valentino, P., van den Brand, F., Vergani, D., Villamil, A., Wahlin, S., Ytting, H., Zachou, K., Zeniya, M., Colapietro, Francesca, Maisonneuve, Patrick, Lytvyak, Ellina, Beuers, Ulrich, Verdonk, Robert C., van der Meer, Adriaan J., van Hoek, Bart, Kuiken, Sjoerd D., Brouwer, Johannes T., Muratori, Paolo, Aghemo, Alessio, Carella, Francesco, van den Berg, Ad P., Zachou, Kalliopi, Dalekos, George N., Di Zeo-Sánchez, Daniel E., Robles, Mercedes, Andrade, Raul J., Montano-Loza, Aldo J., van den Brand, Floris F., Slooter, Charlotte D., Macedo, Guilherme, Liberal, Rodrigo, de Boer, Ynto S., and Lleo, Ana
Published: 2024
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2. A43 LONG-TERM EFFICACY AND SAFETY OF OBETICHOCLIC ACID IN PRIMARY BILIARY CHOLANGITIS: RESPONDER ANALYSIS OF OVER 5 YEARS OF TREATMENT IN THE POISE TRIAL

Author: Hirschfield, G, Jones, D, Carbone, M, Bowlus, CL, Nevens, F, Kremer, AE, Liberman, A, MacConell, L, and Hansen, BE
Abstract: Abstract Background Obeticholic acid (OCA), a potent farnesoid X receptor agonist, is approved as second-line treatment for primary biliary cholangitis (PBC) in patients with an incomplete response or intolerance to ursodeoxycholic acid. Aims We evaluated the effect of OCA in PBC patients enrolled in the POISE trial, comparing those who did or did not achieve the POISE response criteria. Methods The phase 3, randomized, double-blind, 1-year POISE trial evaluated the efficacy and safety of OCA 5 and 10 mg vs placebo in patients with PBC; a 5-year open-label extension followed in which all patients received OCA. This analysis evaluated longer-term efficacy and safety in patients who achieved the POISE primary endpoint of alkaline phosphatase (ALP)
Published: 2021

3. Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation

Author: Montano-Loza, A, Lytvyak, E, Hirschfield, G, Hansen, B, Ebadi, M, Berney, T, Toso, C, Magini, G, Villamil, A, Nevens, F, Van den Ende, N, Pares, A, Ruiz, P, Terrabuio, D, Trivedi, P, Abbas, N, Donato, M, Yu, L, Landis, C, Dumortier, J, Dyson, J, van der Meer, A, de Veer, R, Pedersen, M, Mayo, M, Manns, M, Taubert, R, Kirchner, T, Belli, L, Mazzarelli, C, Stirnimann, G, Floreani, A, Cazzagon, N, Russo, F, Burra, P, Zigmound, U, Houri, I, Carbone, M, Mulinacci, G, Fagiuoli, S, Pratt, D, Bonder, A, Schiano, T, Haydel, B, Lohse, A, Schramm, C, Ruther, D, Casu, S, Verhelst, X, Beretta-Piccoli, B, Robles, M, Mason, A, Corpechot, C, Montano-Loza A. J., Lytvyak E., Hirschfield G., Hansen B. E., Ebadi M., Berney T., Toso C., Magini G., Villamil A., Nevens F., Van den Ende N., Pares A., Ruiz P., Terrabuio D., Trivedi P. J., Abbas N., Donato M. F., Yu L., Landis C., Dumortier J., Dyson J. K., van der Meer A. J., de Veer R., Pedersen M., Mayo M., Manns M. P., Taubert R., Kirchner T., Belli L. S., Mazzarelli C., Stirnimann G., Floreani A., Cazzagon N., Russo F. P., Burra P., Zigmound U., Houri I., Carbone M., Mulinacci G., Fagiuoli S., Pratt D. S., Bonder A., Schiano T. D., Haydel B., Lohse A., Schramm C., Ruther D., Casu S., Verhelst X., Beretta-Piccoli B. T., Robles M., Mason A. L., Corpechot C., Montano-Loza, A, Lytvyak, E, Hirschfield, G, Hansen, B, Ebadi, M, Berney, T, Toso, C, Magini, G, Villamil, A, Nevens, F, Van den Ende, N, Pares, A, Ruiz, P, Terrabuio, D, Trivedi, P, Abbas, N, Donato, M, Yu, L, Landis, C, Dumortier, J, Dyson, J, van der Meer, A, de Veer, R, Pedersen, M, Mayo, M, Manns, M, Taubert, R, Kirchner, T, Belli, L, Mazzarelli, C, Stirnimann, G, Floreani, A, Cazzagon, N, Russo, F, Burra, P, Zigmound, U, Houri, I, Carbone, M, Mulinacci, G, Fagiuoli, S, Pratt, D, Bonder, A, Schiano, T, Haydel, B, Lohse, A, Schramm, C, Ruther, D, Casu, S, Verhelst, X, Beretta-Piccoli, B, Robles, M, Mason, A, Corpechot, C, Montano-Loza A. J., Lytvyak E., Hirschfield G., Hansen B. E., Ebadi M., Berney T., Toso C., Magini G., Villamil A., Nevens F., Van den Ende N., Pares A., Ruiz P., Terrabuio D., Trivedi P. J., Abbas N., Donato M. F., Yu L., Landis C., Dumortier J., Dyson J. K., van der Meer A. J., de Veer R., Pedersen M., Mayo M., Manns M. P., Taubert R., Kirchner T., Belli L. S., Mazzarelli C., Stirnimann G., Floreani A., Cazzagon N., Russo F. P., Burra P., Zigmound U., Houri I., Carbone M., Mulinacci G., Fagiuoli S., Pratt D. S., Bonder A., Schiano T. D., Haydel B., Lohse A., Schramm C., Ruther D., Casu S., Verhelst X., Beretta-Piccoli B. T., Robles M., Mason A. L., and Corpechot C.
Abstract: Background & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2–62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. Results: During a median follow-up of 8.7 years [IQR 4.3–12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. Conclusion: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. Impact and implications: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according
Published: 2024

4. 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

5. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Author: Almasio, P., Alvarez, F., Andrade, R., Arikan, C., Assis, D., Bardou-Jacquet, E., Biewenga, M., Cancado, E., Cazzagon, N., Chazouillères, O., Colloredo, G., Cuarterolo, M., Dalekos, G., Debray, D., Robles-Díaz, M., Drenth, J., Dyson, J., Efe, C., Engel, B., Ferri, S., Fontana, R., Gatselis, N., Gerussi, A., Halilbasic, E., Halliday, N., Heneghan, M., Hirschfield, G., van Hoek, B., Hørby Jørgensen, M., Indolfini, G., Iorio, R., Jeong, S., Jones, D., Kelly, D., Kerkar, N., Lacaille, F., Lammert, C., Leggett, B., Lenzi, M., Levy, C., Liberal, R., Lleo, A., Lohse, A., Ines Lopez, S., de Martin, E., McLin, V., Mieli-Vergani, G., Milkiewicz, P., Mohan, N., Muratori, L., Nebbia, G., van Nieuwkerk, C., Oo, Y., Ortega, A., Páres, A., Pop, T., Pratt, D., Purnak, T., Ranucci, G., Rushbrook, S., Schramm, C., Stättermayer, A., Swain, M., Tanaka, A., Taubert, R., Terrabuio, D., Terziroli, B., Trauner, M., Valentino, P., van den Brand, F., Villamil, A., Wahlin, S., Ytting, H., Zachou, K., Zeniya, M., Pape, Simon, Snijders, Romée J.A.L.M., Gevers, Tom J.G., Chazouilleres, Oliver, Dalekos, George N., Hirschfield, Gideon M., Lenzi, Marco, Trauner, Michael, Manns, Michael P., Vierling, John M., Montano-Loza, Aldo J., Lohse, Ansgar W., Schramm, Christoph, Drenth, Joost P.H., and Heneghan, Michael A.
Published: 2022
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6. Ursodeoxycholic Acid Treatment-Induced GLOBE Score Changes Are Associated With Liver Transplantation-Free Survival in Patients With Primary Biliary Cholangitis

Author: De Veer, R, Van Hooff, M, Corpechot, C, Thorburn, D, Invernizzi, P, Lammers, W, Janssen, H, Battezzati, P, Nevens, F, Lindor, K, Floreani, A, Ponsioen, C, Mayo, M, Pares, A, Mason, A, Kowdley, K, Trivedi, P, Hirschfield, G, Goet, J, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Hansen, B, Harms, M, Van Der Meer, A, De Veer R. C., Van Hooff M. C., Corpechot C., Thorburn D., Invernizzi P., Lammers W. J., Janssen H. L. A., Battezzati P. M., Nevens F., Lindor K. D., Floreani A., Ponsioen C. Y., Mayo M. J., Pares A., Mason A. L., Kowdley K. V., Trivedi P. J., Hirschfield G. M., Goet J. C., Bruns T., Dalekos G. N., Gatselis N. K., Verhelst X., Hansen B. E., Harms M. H., Van Der Meer A. J., De Veer, R, Van Hooff, M, Corpechot, C, Thorburn, D, Invernizzi, P, Lammers, W, Janssen, H, Battezzati, P, Nevens, F, Lindor, K, Floreani, A, Ponsioen, C, Mayo, M, Pares, A, Mason, A, Kowdley, K, Trivedi, P, Hirschfield, G, Goet, J, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Hansen, B, Harms, M, Van Der Meer, A, De Veer R. C., Van Hooff M. C., Corpechot C., Thorburn D., Invernizzi P., Lammers W. J., Janssen H. L. A., Battezzati P. M., Nevens F., Lindor K. D., Floreani A., Ponsioen C. Y., Mayo M. J., Pares A., Mason A. L., Kowdley K. V., Trivedi P. J., Hirschfield G. M., Goet J. C., Bruns T., Dalekos G. N., Gatselis N. K., Verhelst X., Hansen B. E., Harms M. H., and Van Der Meer A. J.
Published: 2023

7. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

Author: Hirschfield, G, Shiffman, M, Gulamhusein, A, Kowdley, K, Vierling, J, Levy, C, Kremer, A, Zigmond, E, Andreone, P, Gordon, S, Bowlus, C, Lawitz, E, Aspinall, R, Pratt, D, Raikhelson, K, Gonzalez-Huezo, M, Heneghan, M, Jeong, S, Ladron De Guevara, A, Mayo, M, Dalekos, G, Drenth, J, Janczewska, E, Leggett, B, Nevens, F, Vargas, V, Zuckerman, E, Corpechot, C, Fassio, E, Hinrichsen, H, Invernizzi, P, Trivedi, P, Forman, L, Jones, D, Ryder, S, Swain, M, Steinberg, A, Boudes, P, Choi, Y, Mcwherter, C, Adrover, R, Agrawal, S, Aigner, E, Martinez, A, Alden, A, Bellido, R, Jimenez, M, Ayoub, W, Baum, S, Ben-Ari, Z, Berenguer, M, Berg, C, Bessone, F, Bonder, A, Borg, B, Ruiz, C, Buggisch, P, Panero, J, Carey, E, Carmiel-Haggai, M, Carubbi, F, Grau, P, Ch'Ng, C, Cimpoeru, N, Omana, R, Corless, L, Costentin, C, Deschenes, M, Dorffel, Y, Dugalic, P, Farrell, G, Fernandez, J, Floreani, A, Francque, S, Freilich, B, Saldias, F, Galambos, M, Galati, J, Galli, A, Ganne-Carrie, N, Geyvandova, N, Gheorghe, L, Gilroy, R, Goel, A, Goeser, T, Greenbloom, S, Halota, W, Harrison, S, Hartleb, M, Heo, J, Hofer, H, Horvath, G, Huang, J, Huffman, J, Hunyady, B, Johnson, S, Kallis, Y, Khazanchi, A, Kim, K, Kim, S, Kim, Y, Kohli, A, Kontorinis, N, Lake, J, Lee, K, Mach, T, Manch, R, Maor-Kendler, Y, Mateescu, R, Minuk, G, Modi, A, Moehlen, M, Rodriguez, C, Cunill, R, Mouzas, I, Muir, A, Nagy, I, Ngu, J, Odin, J, Ogurtsov, P, Pabjan, P, Pagadala, M, Papp, M, Pares, A, Peskov, A, Peyton, A, Phillips, J, Porayko, M, Post, A, Pound, D, Rabinovitz, M, Rank, K, Reddy, K, Regula, J, Riley, T, Gomez, M, Safadi, R, Sheridan, D, Silva, M, Silveira, M, Sood, S, Sporea, I, Stanca, C, Stauber, R, Svorcan, P, Tak, W, Taylor, R, Thorburn, D, Tobias, H, Zekry, A, Trauner, M, Triantos, C, Veitsman, E, Thompson, A, Verhelst, X, Verna, E, Von Der Ohe, M, Weilert, F, Wiegand, J, Yimam, K, Yoon, S, Younes, Z, Zivony, A, Zuin, M, Hirschfield G. M., Shiffman M. L., Gulamhusein A., Kowdley K. V., Vierling J. M., Levy C., Kremer A. E., Zigmond E., Andreone P., Gordon S. C., Bowlus C. L., Lawitz E. J., Aspinall R. J., Pratt D. S., Raikhelson K., Gonzalez-Huezo M. S., Heneghan M. A., Jeong S. -H., Ladron De Guevara A. L., Mayo M. J., Dalekos G. N., Drenth J. P. H., Janczewska E., Leggett B. A., Nevens F., Vargas V., Zuckerman E., Corpechot C., Fassio E., Hinrichsen H., Invernizzi P., Trivedi P. J., Forman L., Jones D. E. J., Ryder S. D., Swain M. G., Steinberg A., Boudes P. F., Choi Y. -J., McWherter C. A., Adrover R., Agrawal S., Aigner E., Martinez A. A., Alden A. -M. S., Bellido R. J. A., Jimenez M. A. A., Ayoub W., Baum S. J., Ben-Ari Z., Berenguer M., Berg C., Bessone F. O., Bonder A., Borg B. B., Ruiz C. G. B., Buggisch P., Panero J. L. C., Carey E. J., Carmiel-Haggai M., Carubbi F., Grau P. C., Ch'ng C. L., Cimpoeru N. -C., Omana R. C., Corless L., Costentin C., Deschenes M., Dorffel Y., Dugalic P., Farrell G. C., Fernandez J. L., Floreani A., Francque S., Freilich B. L., Saldias F. A. F., Galambos M. R., Galati J., Galli A., Ganne-Carrie N., Geyvandova N., Gheorghe L. -S., Gilroy R., Goel A., Goeser T., Greenbloom S., Halota W., Harrison S. A., Hartleb M., Heo J., Hofer H., Horvath G., Huang J. C., Huffman J. L., Hunyady B., Johnson S., Kallis Y., Khazanchi A., Kim K. -A., Kim S. U., Kim Y. J., Kohli A., Kontorinis N., Lake J. R., Lee K. S., Mach T., Manch R., Maor-Kendler Y., Mateescu R. -B., Minuk G., Modi A. A., Moehlen M. W., Rodriguez C. M., Cunill R. M. M., Mouzas I., Muir A., Nagy I., Ngu J. H. (., Odin J., Ogurtsov P., Pabjan P., Pagadala M., Papp M., Pares A., Peskov A., Peyton A., Phillips J., Porayko M., Post A., Pound D. C., Rabinovitz M., Rank K., Reddy K. G., Regula J., Riley T., Gomez M. R., Safadi R., Sheridan D. A., Silva M. O., Silveira M. G., Sood S., Sporea I., Stanca C., Stauber R., Svorcan P., Tak W. Y., Taylor R. M., Thorburn D., Tobias H., Zekry A. T., Trauner M., Triantos C., Veitsman E., Thompson A. J. V., Verhelst X., Verna E. C., Von Der Ohe M., Weilert F., Wiegand J., Yimam K. K., Yoon S. K., Younes Z., Zivony A. S., Zuin M., Hirschfield, G, Shiffman, M, Gulamhusein, A, Kowdley, K, Vierling, J, Levy, C, Kremer, A, Zigmond, E, Andreone, P, Gordon, S, Bowlus, C, Lawitz, E, Aspinall, R, Pratt, D, Raikhelson, K, Gonzalez-Huezo, M, Heneghan, M, Jeong, S, Ladron De Guevara, A, Mayo, M, Dalekos, G, Drenth, J, Janczewska, E, Leggett, B, Nevens, F, Vargas, V, Zuckerman, E, Corpechot, C, Fassio, E, Hinrichsen, H, Invernizzi, P, Trivedi, P, Forman, L, Jones, D, Ryder, S, Swain, M, Steinberg, A, Boudes, P, Choi, Y, Mcwherter, C, Adrover, R, Agrawal, S, Aigner, E, Martinez, A, Alden, A, Bellido, R, Jimenez, M, Ayoub, W, Baum, S, Ben-Ari, Z, Berenguer, M, Berg, C, Bessone, F, Bonder, A, Borg, B, Ruiz, C, Buggisch, P, Panero, J, Carey, E, Carmiel-Haggai, M, Carubbi, F, Grau, P, Ch'Ng, C, Cimpoeru, N, Omana, R, Corless, L, Costentin, C, Deschenes, M, Dorffel, Y, Dugalic, P, Farrell, G, Fernandez, J, Floreani, A, Francque, S, Freilich, B, Saldias, F, Galambos, M, Galati, J, Galli, A, Ganne-Carrie, N, Geyvandova, N, Gheorghe, L, Gilroy, R, Goel, A, Goeser, T, Greenbloom, S, Halota, W, Harrison, S, Hartleb, M, Heo, J, Hofer, H, Horvath, G, Huang, J, Huffman, J, Hunyady, B, Johnson, S, Kallis, Y, Khazanchi, A, Kim, K, Kim, S, Kim, Y, Kohli, A, Kontorinis, N, Lake, J, Lee, K, Mach, T, Manch, R, Maor-Kendler, Y, Mateescu, R, Minuk, G, Modi, A, Moehlen, M, Rodriguez, C, Cunill, R, Mouzas, I, Muir, A, Nagy, I, Ngu, J, Odin, J, Ogurtsov, P, Pabjan, P, Pagadala, M, Papp, M, Pares, A, Peskov, A, Peyton, A, Phillips, J, Porayko, M, Post, A, Pound, D, Rabinovitz, M, Rank, K, Reddy, K, Regula, J, Riley, T, Gomez, M, Safadi, R, Sheridan, D, Silva, M, Silveira, M, Sood, S, Sporea, I, Stanca, C, Stauber, R, Svorcan, P, Tak, W, Taylor, R, Thorburn, D, Tobias, H, Zekry, A, Trauner, M, Triantos, C, Veitsman, E, Thompson, A, Verhelst, X, Verna, E, Von Der Ohe, M, Weilert, F, Wiegand, J, Yimam, K, Yoon, S, Younes, Z, Zivony, A, Zuin, M, Hirschfield G. M., Shiffman M. L., Gulamhusein A., Kowdley K. V., Vierling J. M., Levy C., Kremer A. E., Zigmond E., Andreone P., Gordon S. C., Bowlus C. L., Lawitz E. J., Aspinall R. J., Pratt D. S., Raikhelson K., Gonzalez-Huezo M. S., Heneghan M. A., Jeong S. -H., Ladron De Guevara A. L., Mayo M. J., Dalekos G. N., Drenth J. P. H., Janczewska E., Leggett B. A., Nevens F., Vargas V., Zuckerman E., Corpechot C., Fassio E., Hinrichsen H., Invernizzi P., Trivedi P. J., Forman L., Jones D. E. J., Ryder S. D., Swain M. G., Steinberg A., Boudes P. F., Choi Y. -J., McWherter C. A., Adrover R., Agrawal S., Aigner E., Martinez A. A., Alden A. -M. S., Bellido R. J. A., Jimenez M. A. A., Ayoub W., Baum S. J., Ben-Ari Z., Berenguer M., Berg C., Bessone F. O., Bonder A., Borg B. B., Ruiz C. G. B., Buggisch P., Panero J. L. C., Carey E. J., Carmiel-Haggai M., Carubbi F., Grau P. C., Ch'ng C. L., Cimpoeru N. -C., Omana R. C., Corless L., Costentin C., Deschenes M., Dorffel Y., Dugalic P., Farrell G. C., Fernandez J. L., Floreani A., Francque S., Freilich B. L., Saldias F. A. F., Galambos M. R., Galati J., Galli A., Ganne-Carrie N., Geyvandova N., Gheorghe L. -S., Gilroy R., Goel A., Goeser T., Greenbloom S., Halota W., Harrison S. A., Hartleb M., Heo J., Hofer H., Horvath G., Huang J. C., Huffman J. L., Hunyady B., Johnson S., Kallis Y., Khazanchi A., Kim K. -A., Kim S. U., Kim Y. J., Kohli A., Kontorinis N., Lake J. R., Lee K. S., Mach T., Manch R., Maor-Kendler Y., Mateescu R. -B., Minuk G., Modi A. A., Moehlen M. W., Rodriguez C. M., Cunill R. M. M., Mouzas I., Muir A., Nagy I., Ngu J. H. (., Odin J., Ogurtsov P., Pabjan P., Pagadala M., Papp M., Pares A., Peskov A., Peyton A., Phillips J., Porayko M., Post A., Pound D. C., Rabinovitz M., Rank K., Reddy K. G., Regula J., Riley T., Gomez M. R., Safadi R., Sheridan D. A., Silva M. O., Silveira M. G., Sood S., Sporea I., Stanca C., Stauber R., Svorcan P., Tak W. Y., Taylor R. M., Thorburn D., Tobias H., Zekry A. T., Trauner M., Triantos C., Veitsman E., Thompson A. J. V., Verhelst X., Verna E. C., Von Der Ohe M., Weilert F., Wiegand J., Yimam K. K., Yoon S. K., Younes Z., Zivony A. S., and Zuin M.
Published: 2023

8. 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

9. 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

10. Corrigendum to: “An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs” [J Hepatol 75 (2021) 572-581, (S0168827821003342), (10.1016/j.jhep.2021.04.055)]

Author: Cordell H. J., Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Cordell H. J., Fryett J. J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S. -S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B. D., Atkinson E. J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M. A. R., Sun D., Jones D. E., Flack S., Spicer A., Mulcahy V. L., Byan J., Han Y., Sandford R. N., Lazaridis K. N., Amos C. I., Hirschfield G. M., Seldin M. F., Invernizzi P., Siminovitch K. A., Ma X., Nakamura M., Mells G. F., Cordell H. J., Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Cordell H. J., Fryett J. J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S. -S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B. D., Atkinson E. J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M. A. R., Sun D., Jones D. E., Flack S., Spicer A., Mulcahy V. L., Byan J., Han Y., Sandford R. N., Lazaridis K. N., Amos C. I., Hirschfield G. M., Seldin M. F., Invernizzi P., Siminovitch K. A., Ma X., Nakamura M., and Mells G. F.
Abstract: It has come to our attention that while we explained that data for the control group in our study was provided by Understanding Society, we did not include the required statement for use of these data, which is the following: “Understanding Society: The UK Household Longitudinal Study is led by the Institute for Social and Economic Research at the University of Essex and funded by the Economic and Social Research Council. The survey was conducted by NatCen and the genome-wide scan data were analysed and deposited by the Wellcome Trust Sanger Institute. Information on how to access the data can be found on the Understanding Society website https://www.understandingsociety.ac.uk/.” We apologise for any inconvenience caused.
Published: 2023

11. A114 IMPROVING THE QUALITY OF PARACENTESIS PRACTICES IN PEOPLE WITH ADVANCED CIRRHOSIS IN AN AMBULATORY CARE SETTING

Author: Sedarous, M, primary, Lee, E, additional, Verma, A, additional, Quinn, K, additional, and Hirschfield, G, additional
Published: 2024
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12. A280 HEPATOBILIARY DISEASE IN INDIVIDUALS LIVING WITH FRAGILE X SYNDROME: A CASE SERIES

Author: Alalool, A, primary, Hirschfield, G, additional, and Leung, K, additional
Published: 2024
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13. A296 ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY AND PRIMARY SCLEROSING CHOLANGITIS: A RETROSPECTIVE STUDY OF A HIGH-VOLUME PROGRAMME

Author: Leung, K, primary, Youssef, M, additional, Xiao, Y, additional, Streutker, C, additional, Calo, N, additional, Gulamhusein, A, additional, Hansen, B, additional, May, G, additional, Mosko, J, additional, and Hirschfield, G, additional
Published: 2024
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14. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Author: Colapietro, Francesca, primary, Maisonneuve, Patrick, additional, Lytvyak, Ellina, additional, Beuers, Ulrich, additional, Verdonk, Robert C., additional, van der Meer, Adriaan J., additional, van Hoek, Bart, additional, Kuiken, Sjoerd D., additional, Brouwer, Johannes T., additional, Muratori, Paolo, additional, Aghemo, Alessio, additional, Carella, Francesco, additional, van den Berg, Ad P., additional, Zachou, Kalliopi, additional, Dalekos, George N., additional, Di Zeo-Sánchez, Daniel E., additional, Robles, Mercedes, additional, Andrade, Raul J., additional, Montano-Loza, Aldo J., additional, van den Brand, Floris F., additional, Slooter, Charlotte D., additional, Macedo, Guilherme, additional, Liberal, Rodrigo, additional, de Boer, Ynto S., additional, Lleo, Ana, additional, van Gerven, N., additional, van Erpecum, K., additional, Ouden, J den, additional, Brouwer, J., additional, Vrolijk, J., additional, Gevers, T.J., additional, Drenth, J., additional, Guichelaar, M., additional, Bouma, G., additional, Schreuder, T.C.M.A., additional, van der Wouden, E.J., additional, Baak, L.C., additional, Stadhouders, P., additional, Klemt-Kropp, M., additional, Verhagen, M., additional, Bhalla, A., additional, Kuijvenhoven, J., additional, Almasio, P., additional, Alvarez, F., additional, Andrade, R., additional, Arikan, C., additional, Assis, D., additional, Bardou-Jacquet, E., additional, Biewenga, M., additional, Cancado, E., additional, Cazzagon, N., additional, Chazouillères, O., additional, Colloredo, G., additional, Cuarterolo, M., additional, Dalekos, G., additional, Debray, D., additional, Robles-Díaz, M., additional, Dyson, J., additional, Efe, C., additional, Engel, B., additional, Ferri, S., additional, Fontana, R., additional, Gatselis, N., additional, Gerussi, A., additional, Halilbasic, E., additional, Halliday, N., additional, Heneghan, M., additional, Hirschfield, G., additional, van Hoek, B., additional, Hørby Jørgensen, M., additional, Indolfini, G., additional, Iorio, R., additional, Invernizzi, P., additional, Jeong, S., additional, Jones, D., additional, Kelly, D., additional, Kerkar, N., additional, Lacaille, F., additional, Lammert, C., additional, Leggett, B., additional, Lenzi, M., additional, Levy, C., additional, Liberal, R., additional, Lleo, A., additional, Lohse, A., additional, Lopez, S. Ines, additional, de Martin, E., additional, McLin, V., additional, Mieli-Vergani, G., additional, Milkiewicz, P., additional, Mohan, N., additional, Muratori, L., additional, Nebbia, G., additional, van Nieuwkerk, C., additional, Oo, Y., additional, Ortega, A., additional, Páres, A., additional, Pop, T., additional, Pratt, D., additional, Purnak, T., additional, Ranucci, G., additional, Rushbrook, S., additional, Schramm, C., additional, Stättermayer, A., additional, Swain, M., additional, Tanaka, A., additional, Taubert, R., additional, Terrabuio, D., additional, Terziroli, B., additional, Trauner, M., additional, Valentino, P., additional, van den Brand, F., additional, Vergani, D., additional, Villamil, A., additional, Wahlin, S., additional, Ytting, H., additional, Zachou, K., additional, and Zeniya, M., additional
Published: 2023
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15. Longer transplant-free and liver-related event-free survival in obeticholic acid-treated patients with primary biliary cholangitis compared to external controls from two large real-world cohorts

Author: Terracciani, F., De Vincentis, A., D'Amato, D., Invernizzi, P., Morgando, A., Vanni, E., Viganò, M., Alvaro, D., Venere, R., Lleo, A., Colapietro, F., Degasperi, E., Viganò, R., Giannini, E.G., Labanca, S., Feletti, V., Mussetto, A., Cozzolongo, R., Losito, F., Pompili, M., Ponziani, F.R., Niro, G.A., Cotugno, R., Pozzoni, P., Chessa, L., Cuccorese, G., Pace Palitti, V., Russello, M., Cannavò, M., Frazzetto, E., Bertino, G., Marzioni, M., Terreni, N., Zolfino, T., Saitta, C., Pellicelli, A., Coco, B., Brunetto, M., Cazzagon, N., Floreani, A., Muratori, L., Rosina, F., Stefano, M. Di, Scifo, G., Baiocchi, L., Grassi, G., Sacco, R., Izzi, A., Crocè, S.L., Fiorini, C., Marra, F., Galli, A., Simone, L., Morelli, O., Abenavoli, L., Pizzolante, F., De Matthaeis, N., Scaravaglio, M., Gimignani, G., Boano, V., Manfredi, G.F., Marignani, M., Fanella, S., Giacchetto, M., Castellaneta, A., Poggi, G., Buzzanca, V., Scivetti, P., Tortora, A., Casella, S., Bellia, V., Omazzi, B.F., Alagna, G., Ricci, C., Poisa, P., Rigamonti, C., Calvaruso, V., Corpechot, C., Carrat, F., Hirschfield, G., Gulamhusein, A., Levy, C., Tananka, A., Montano-Loza, A. J, Londono, M., Eaton, J. E, Dalekos, G. N, Gatselis, N., Abbas, N., Trivedi, P., Thorburn, D., Bonder, A., van der Meer, A., Zigmond, E., Kremer, A. E, Bruns, T., Chazouilleres, O., Hansen, B. E, Carbone, M., and Vespasiani-Gentilucci, U.
Published: 2024
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16. 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

17. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

Author: Cordell H. 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F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, 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A., Overton J. D., Reid J. G., Shuldiner A., Beechert C., Forsythe C., Fuller E. D., Gu Z., Lattari M., Lopez A., Schleicher T. D., Padilla M. S., Toledo K., Widom L., Wolf S. E., Pradhan M., Manoochehri K., Ulloa R. H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E. K., Salerno W., Staples J. C., Jones M. B., Mitnaul L. J., Sturgess R., Healey C., Yeoman A., Gunasekera A. V. J., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J. A., Gorard D. A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M. R., Collins C. E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M. J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I. R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H. M., Ridpath J., Ngatchu T., Bob Grover V. P., Shidrawi R. G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M. A., Curtis H., Matthews H. C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M. I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N. N., Gupta P., Shah A., Evans C. D. J., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S. T., McDonald N., Bathgate A. J., Palmer K., Dillon J. F., Rushbrook S. M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T. J. W., Ryder S., Collier J., Klass H., Cramp M. E., Sharer N., Aspinall R., Ghosh D., Douds A. C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C. L., Rahman M., Whatley G. C. A., Wesley E., Mandal A., Jain S., Pereira S. P., Wright M., Trivedi P., Gordon F. H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A. D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S. J., Bell A., Wong V. S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Tarocchi M., Cordell H. J., Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byun, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Tarocchi, M, Cordell H. J., Fryett J. J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S. -S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B. D., Atkinson E. J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M. A. R., Sun D., Jones D. E., Flack S., Spicer A., Mulcahy V. L., Byun J., Han Y., Sandford R. N., Lazaridis K. N., Amos C. I., Hirschfield G. M., Seldin M. F., Invernizzi P., Siminovitch K. A., Ma X., Nakamura M., Mells G. F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P. L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P. M., Benedetti A., Bragazzi M. C., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L. S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G. A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L. A., Overton J. D., Reid J. G., Shuldiner A., Beechert C., Forsythe C., Fuller E. D., Gu Z., Lattari M., Lopez A., Schleicher T. D., Padilla M. S., Toledo K., Widom L., Wolf S. E., Pradhan M., Manoochehri K., Ulloa R. H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E. K., Salerno W., Staples J. C., Jones M. B., Mitnaul L. J., Sturgess R., Healey C., Yeoman A., Gunasekera A. V. J., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J. A., Gorard D. A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M. R., Collins C. E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M. J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I. R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H. M., Ridpath J., Ngatchu T., Bob Grover V. P., Shidrawi R. G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M. A., Curtis H., Matthews H. C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M. I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N. N., Gupta P., Shah A., Evans C. D. J., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S. T., McDonald N., Bathgate A. J., Palmer K., Dillon J. F., Rushbrook S. M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T. J. W., Ryder S., Collier J., Klass H., Cramp M. E., Sharer N., Aspinall R., Ghosh D., Douds A. C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C. L., Rahman M., Whatley G. C. A., Wesley E., Mandal A., Jain S., Pereira S. P., Wright M., Trivedi P., Gordon F. H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A. D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S. J., Bell A., Wong V. S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., and Tarocchi M.
Abstract: It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused.
Published: 2022

18. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Author: Pape, S, Snijders, R, Gevers, T, Chazouilleres, O, Dalekos, G, Hirschfield, G, Lenzi, M, Trauner, M, Manns, M, Vierling, J, Montano-Loza, A, Lohse, A, Schramm, C, Drenth, J, Heneghan, M, Almasio, P, Alvarez, F, Andrade, R, Arikan, C, Assis, D, Bardou-Jacquet, E, Biewenga, M, Cancado, E, Cazzagon, N, Colloredo, G, Cuarterolo, M, Debray, D, Robles-Diaz, M, Dyson, J, Efe, C, Engel, B, Ferri, S, Fontana, R, Gatselis, N, Gerussi, A, Halilbasic, E, Halliday, N, van Hoek, B, Horby Jorgensen, M, Indolfini, G, Iorio, R, Jeong, S, Jones, D, Kelly, D, Kerkar, N, Lacaille, F, Lammert, C, Leggett, B, Levy, C, Liberal, R, Lleo, A, Ines Lopez, S, de Martin, E, Mclin, V, Mieli-Vergani, G, Milkiewicz, P, Mohan, N, Muratori, L, Nebbia, G, van Nieuwkerk, C, Oo, Y, Ortega, A, Pares, A, Pop, T, Pratt, D, Purnak, T, Ranucci, G, Rushbrook, S, Stattermayer, A, Swain, M, Tanaka, A, Taubert, R, Terrabuio, D, Terziroli, B, Valentino, P, van den Brand, F, Villamil, A, Wahlin, S, Ytting, H, Zachou, K, Zeniya, M, Pape S., Snijders R. J. A. L. M., Gevers T. J. G., Chazouilleres O., Dalekos G. N., Hirschfield G. M., Lenzi M., Trauner M., Manns M. P., Vierling J. M., Montano-Loza A. J., Lohse A. W., Schramm C., Drenth J. P. H., Heneghan M. A., Almasio P., Alvarez F., Andrade R., Arikan C., Assis D., Bardou-Jacquet E., Biewenga M., Cancado E., Cazzagon N., Colloredo G., Cuarterolo M., Dalekos G., Debray D., Robles-Diaz M., Drenth J., Dyson J., Efe C., Engel B., Ferri S., Fontana R., Gatselis N., Gerussi A., Halilbasic E., Halliday N., Heneghan M., Hirschfield G., van Hoek B., Horby Jorgensen M., Indolfini G., Iorio R., Jeong S., Jones D., Kelly D., Kerkar N., Lacaille F., Lammert C., Leggett B., Levy C., Liberal R., Lleo A., Lohse A., Ines Lopez S., de Martin E., McLin V., Mieli-Vergani G., Milkiewicz P., Mohan N., Muratori L., Nebbia G., van Nieuwkerk C., Oo Y., Ortega A., Pares A., Pop T., Pratt D., Purnak T., Ranucci G., Rushbrook S., Stattermayer A., Swain M., Tanaka A., Taubert R., Terrabuio D., Terziroli B., Valentino P., van den Brand F., Villamil A., Wahlin S., Ytting H., Zachou K., Zeniya M., Pape, S, Snijders, R, Gevers, T, Chazouilleres, O, Dalekos, G, Hirschfield, G, Lenzi, M, Trauner, M, Manns, M, Vierling, J, Montano-Loza, A, Lohse, A, Schramm, C, Drenth, J, Heneghan, M, Almasio, P, Alvarez, F, Andrade, R, Arikan, C, Assis, D, Bardou-Jacquet, E, Biewenga, M, Cancado, E, Cazzagon, N, Colloredo, G, Cuarterolo, M, Debray, D, Robles-Diaz, M, Dyson, J, Efe, C, Engel, B, Ferri, S, Fontana, R, Gatselis, N, Gerussi, A, Halilbasic, E, Halliday, N, van Hoek, B, Horby Jorgensen, M, Indolfini, G, Iorio, R, Jeong, S, Jones, D, Kelly, D, Kerkar, N, Lacaille, F, Lammert, C, Leggett, B, Levy, C, Liberal, R, Lleo, A, Ines Lopez, S, de Martin, E, Mclin, V, Mieli-Vergani, G, Milkiewicz, P, Mohan, N, Muratori, L, Nebbia, G, van Nieuwkerk, C, Oo, Y, Ortega, A, Pares, A, Pop, T, Pratt, D, Purnak, T, Ranucci, G, Rushbrook, S, Stattermayer, A, Swain, M, Tanaka, A, Taubert, R, Terrabuio, D, Terziroli, B, Valentino, P, van den Brand, F, Villamil, A, Wahlin, S, Ytting, H, Zachou, K, Zeniya, M, Pape S., Snijders R. J. A. L. M., Gevers T. J. G., Chazouilleres O., Dalekos G. N., Hirschfield G. M., Lenzi M., Trauner M., Manns M. P., Vierling J. M., Montano-Loza A. J., Lohse A. W., Schramm C., Drenth J. P. H., Heneghan M. A., Almasio P., Alvarez F., Andrade R., Arikan C., Assis D., Bardou-Jacquet E., Biewenga M., Cancado E., Cazzagon N., Colloredo G., Cuarterolo M., Dalekos G., Debray D., Robles-Diaz M., Drenth J., Dyson J., Efe C., Engel B., Ferri S., Fontana R., Gatselis N., Gerussi A., Halilbasic E., Halliday N., Heneghan M., Hirschfield G., van Hoek B., Horby Jorgensen M., Indolfini G., Iorio R., Jeong S., Jones D., Kelly D., Kerkar N., Lacaille F., Lammert C., Leggett B., Levy C., Liberal R., Lleo A., Lohse A., Ines Lopez S., de Martin E., McLin V., Mieli-Vergani G., Milkiewicz P., Mohan N., Muratori L., Nebbia G., van Nieuwkerk C., Oo Y., Ortega A., Pares A., Pop T., Pratt D., Purnak T., Ranucci G., Rushbrook S., Stattermayer A., Swain M., Tanaka A., Taubert R., Terrabuio D., Terziroli B., Valentino P., van den Brand F., Villamil A., Wahlin S., Ytting H., Zachou K., and Zeniya M.
Abstract: Background & Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘<50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents
Published: 2022

19. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

Author: Hirschfield, G. M., Bowlus, C. L., Mayo, M. J., Kremer, A. E., Vierling, J. M., Kowdley, K. V., Levy, C., Villamil, A., de Guevara Cetina, A. L. Ladrón, Janczewska, E., Zigmond, E., Jeong, S.-H., Yilmaz, Y., Kallis, Y., Corpechot, C., Buggisch, P., Invernizzi, P., Londoño Hurtado, M. C., Bergheanu, S., and Yang, K.
Subjects: *CLINICAL trials, *CHOLANGITIS, *PEROXISOME proliferator-activated receptors, *ALKALINE phosphatase, *URSODEOXYCHOLIC acid
Abstract: BACKGROUND Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits. METHODS In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus). RESULTS Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P=0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively. CONCLUSIONS In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733. opens in new tab; EudraCT number, 2020-004348-27.) [ABSTRACT FROM AUTHOR]
Published: 2024
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20. A245 A TERTIARY CENTRE REVIEW OF PORTO-SYSTEMIC SHUNTS: AN INCREASINGLY IMPORTANT TOOL IN LIVER DISEASE MANAGEMENT

Author: Malik, S, primary, Hirschfield, G, additional, and Jaberi, A, additional
Published: 2023
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21. A44 A 1000 PATIENT CANADIAN NETWORK FOR AUTOIMMUNE LIVER DISEASE EVALUATION OF CLINICAL AND DEMOGRAPHIC PATTERNS OF AUTOIMMUNE HEPATITIS

Author: Plagiannakos, C G, primary, Montano-Loza, A J, additional, Lytvyak, E, additional, Pallotta, J, additional, Mason, A L, additional, Qumosani, K M, additional, Worobetz, L, additional, Flemming, J A, additional, Hercun, J, additional, Vincent, C, additional, Cheung, A, additional, Chen, T, additional, Grbic, D, additional, Swain, M G, additional, Gulamhusein, A, additional, Hansen, B E, additional, and Hirschfield, G M, additional
Published: 2023
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22. A42 LIVE DONOR LIVER TRANSPLANTATION IN PRIMARY SCLEROSING CHOLANGITIS: AN INDICATOR OF AN ORGAN ALLOCATION SYSTEM NOT ADDRESSING PATIENT NEED

Author: Zheng, K, primary, Onofrio, F, additional, Xu, C, additional, Chen, S, additional, Xu, W, additional, Vyas, M, additional, Bingham, K, additional, Patel, K, additional, Lilly, L, additional, Selzner, N, additional, Jaeckel, E, additional, Tsien, C, additional, Gulamhusein, A, additional, Hirschfield, G M, additional, and Bhat, M, additional
Published: 2023
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23. Improving quality of life in patients with rare autoimmune liver diseases by structured peer-delivered support (Q.RARE.LI): Study protocol for a transnational effectiveness-implementation hybrid trial

Author: Uhlenbusch, N., Bal, A., Boglárka, B., Braun, A., Geerts, A., Hirschfield, G., Janik, M., Lohse, A.W., Milkiewicz, P., Papp, M., Poppe, C., Schramm, C., and Löwe, B.
Published: 2023
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24. 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

25. Effects of Primary Biliary Cholangitis on Quality of Life and Health Care Costs in the United Kingdom

Author: Rice, S, Albani, V, Minos, D, Fattakhova, G, Mells, G, Carbone, M, Flack, S, Varvaropoulou, N, Badrock, J, Spicer, A, Sandford, R, Shirley, M, Coughlan, D, Hirschfield, G, Taylor-Robinson, S, Vale, L, Jones, D, Rice S., Albani V., Minos D., Fattakhova G., Mells G. F., Carbone M., Flack S., Varvaropoulou N., Badrock J., Spicer A., Sandford R. N., Shirley M. D. F., Coughlan D., Hirschfield G., Taylor-Robinson S. D., Vale L., Jones D. E. J., Rice, S, Albani, V, Minos, D, Fattakhova, G, Mells, G, Carbone, M, Flack, S, Varvaropoulou, N, Badrock, J, Spicer, A, Sandford, R, Shirley, M, Coughlan, D, Hirschfield, G, Taylor-Robinson, S, Vale, L, Jones, D, Rice S., Albani V., Minos D., Fattakhova G., Mells G. F., Carbone M., Flack S., Varvaropoulou N., Badrock J., Spicer A., Sandford R. N., Shirley M. D. F., Coughlan D., Hirschfield G., Taylor-Robinson S. D., Vale L., and Jones D. E. J.
Abstract: Background & Aims: There have been few high-quality studies of the costs, preference-based health-related quality of life (HRQoL) and cost effectiveness of treatments for primary biliary cholangitis (PBC). We aimed to estimate the marginal effects of PBC complications and symptoms, accounting for treatment, on HRQoL and the annual cost of health care in the United Kingdom (UK). These are essential components for evaluation of cost effectiveness and this information will aid in evaluation of new treatments. Methods: Questionnaires were mailed to 4583 participants in the UK-PBC research cohort and data were collected on HRQoL and use of the National Health Service (NHS) in the UK from 2015 through 2016. HRQoL was measured using the EQ-5D-5L instrument. The annual cost of resource use was calculated using unit costs obtained from NHS sources. We performed econometric analyses to determine the effects of treatment, symptoms, complications, liver transplantation status, and patient characteristics on HRQoL and annual costs. Results: In an analysis of data from 2240 participants (over 10% of all UK PBC patients), we found that PBC symptoms have a considerable effect on HRQoL. Ursodeoxycholic acid therapy was associated with significantly higher HRQoL regardless of response status. Having had a liver transplant and ascites were also independently associated with reduced HRQoL. Having had a liver transplant (US$4294) and esophageal varices (US$3401) were the factors with the two greatest mean annual costs to the NHS. Symptoms were not independently associated with cost but were associated with reduction in HRQoL for patients, indicating the lack of effective treatments for PBC symptoms. Conclusions: In an analysis of data from 2240 participants in the UK PBC, we found that HRQoL and cost estimates provide greater insight into the relative importance of PBC-related symptoms and complications. These findings provide estimates for health technology assessments of new treat
Published: 2021

26. A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients

Author: Hirschfield, G, Chazouilleres, O, Cortez-Pinto, H, Macedo, G, de Ledinghen, V, Adekunle, F, Carbone, M, Hirschfield G. M., Chazouilleres O., Cortez-Pinto H., Macedo G., de Ledinghen V., Adekunle F., Carbone M., Hirschfield, G, Chazouilleres, O, Cortez-Pinto, H, Macedo, G, de Ledinghen, V, Adekunle, F, Carbone, M, Hirschfield G. M., Chazouilleres O., Cortez-Pinto H., Macedo G., de Ledinghen V., Adekunle F., and Carbone M.
Abstract: Introduction: Primary biliary cholangitis (PBC) is an infrequent, immune-mediated cholestatic liver disease, which can lead to liver fibrosis, cirrhosis and complications of end-stage liver disease. The established goals of treatment of PBC are prevention of end-stage liver disease and amelioration of associated symptoms. The European Association for the Study of the Liver (EASL) management guidelines provide extensive recommendations on the diagnosis and management of PBC. Areas covered: This article describes the development by expert consensus of a ‘PBC Integrated Patient Care Pathway’ to simplify and standardize the management of PBC for clinicians based on current practice. Expert opinion: Guideline adoption is potentially poor in practice since most patients with PBC in the community are seen by general gastroenterologists or hepatologists without a special interest in autoimmune liver disease. The PBC Integrated Patient Care Pathway is a best practice tool for clinicians designed to complement the EASL Clinical Practice Guidelines for the diagnosis and management of PBC patients. It gives clinicians a practical decision tree of the key steps in PBC management, thereby providing a simplified framework and an opportunity for more uniform practice that supports the safe and timely adoption of varied models of care provision to patients with PBC.
Published: 2021

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

Author: Goet, J, Murillo Perez, C, Harms, M, Floreani, A, Cazzagon, N, Bruns, T, Prechter, F, Dalekos, G, Verhelst, X, Gatselis, N, Lindor, K, Lammers, W, Gulamhusein, A, Reig, A, Carbone, M, Nevens, F, Hirschfield, G, van der Meer, A, van Buuren, H, Hansen, B, Pares, A, Goet J. C., Murillo Perez C. F., Harms M. H., Floreani A., Cazzagon N., Bruns T., Prechter F., Dalekos G. N., Verhelst X., Gatselis N. K., Lindor K. D., Lammers W. J., Gulamhusein A., Reig A., Carbone M., Nevens F., Hirschfield G. M., van der Meer A. J., van Buuren H. R., Hansen B. E., Pares A., Goet, J, Murillo Perez, C, Harms, M, Floreani, A, Cazzagon, N, Bruns, T, Prechter, F, Dalekos, G, Verhelst, X, Gatselis, N, Lindor, K, Lammers, W, Gulamhusein, A, Reig, A, Carbone, M, Nevens, F, Hirschfield, G, van der Meer, A, van Buuren, H, Hansen, B, Pares, A, Goet J. C., Murillo Perez C. F., Harms M. H., Floreani A., Cazzagon N., Bruns T., Prechter F., Dalekos G. N., Verhelst X., Gatselis N. K., Lindor K. D., Lammers W. J., Gulamhusein A., Reig A., Carbone M., Nevens F., Hirschfield G. M., van der Meer A. J., van Buuren H. R., Hansen B. E., and Pares A.
Abstract: INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.
Published: 2021

28. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Author: Asselta, R, Paraboschi, E, Gerussi, A, Cordell, H, Mells, G, Sandford, R, Jones, D, Nakamura, M, Ueno, K, Hitomi, Y, Kawashima, M, Nishida, N, Tokunaga, K, Nagasaki, M, Tanaka, A, Tang, R, Li, Z, Shi, Y, Liu, X, Xiong, M, Hirschfield, G, Siminovitch, K, Walker, E, Xie, G, Mason, A, Myers, R, Peltekian, K, Ghent, C, Atkinson, E, Juran, B, Lazaridis, K, Lu, Y, Gu, X, Jing, K, Amos, C, Affronti, A, Brunetto, M, Coco, B, Spinzi, G, Elia, G, Ferrari, C, Lleo, A, Muratori, L, Muratori, P, Portincasa, P, Colli, A, Bruno, S, Colloredo, G, Azzaroli, F, Andreone, P, Bragazzi, M, Alvaro, D, Cardinale, V, Cazzagon, N, Rigamonti, C, Floreani, A, Rosina, F, Ciaccio, A, Cristoferi, L, D'Amato, D, Malinverno, F, Mancuso, C, Massironi, S, Milani, C, O'Donnell, S, Ronca, V, Barisani, D, Lampertico, P, Donato, F, Fagiuoli, S, Almasio, P, Giannini, E, Cursaro, C, Colombo, M, Valenti, L, Miele, L, Andriulli, A, Niro, G, Grattagliano, I, Morini, L, Casella, G, Vinci, M, Battezzati, P, Crosignani, A, Zuin, M, Mattalia, A, Calvaruso, V, Colombo, S, Benedetti, A, Marzioni, M, Galli, A, Marra, F, Tarocchi, M, Picciotto, A, Morisco, F, Fabris, L, Croce, L, Tiribelli, C, Toniutto, P, Strazzabosco, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Alexander, G, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Taylor-Robinson, S, Williams, S, Grellier, L, Banim, P, Das, D, Chilton, A, Heneghan, M, Curtis, H, Gess, M, Drake, I, Aldersley, M, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Bathgate, A, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Thorburn, D, Marshall, E, Burroughs, A, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Neuberger, J, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney-Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali-kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordula, J, Aiba, Y, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Kawai, Y, Kohn, S, Gervais, O, Migita, K, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Higuchi, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Takikawa, H, Ohira, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Carbone, M, Cardamone, G, Duga, S, Gershwin, M, Seldin, M, Invernizzi, P, Asselta R., Paraboschi E. M., Gerussi A., Cordell H. J., Mells G. F., Sandford R. N., Jones D. E., Nakamura M., Ueno K., Hitomi Y., Kawashima M., Nishida N., Tokunaga K., Nagasaki M., Tanaka A., Tang R., Li Z., Shi Y., Liu X., Xiong M., Hirschfield G., Siminovitch K. A., Walker E., Xie G., Mason A., Myers R., Peltekian K., Ghent C., Atkinson E., Juran B., Lazaridis K., Lu Y., Gu X., Jing K., Amos C., Affronti A., Brunetto M., Coco B., Spinzi G., Elia G., Ferrari C., Lleo A., Muratori L., Muratori P., Portincasa P., Colli A., Bruno S., Colloredo G., Azzaroli F., Andreone P., Bragazzi M., Alvaro D., Cardinale V., Cazzagon N., Rigamonti C., Floreani A., Rosina F., Ciaccio A., Cristoferi L., D'Amato D., Malinverno F., Mancuso C., Massironi S., Milani C., O'Donnell S. E., Ronca V., Barisani D., Lampertico P., Donato F., Fagiuoli S., Almasio P. L., Giannini E., Cursaro C., Colombo M., Valenti L., Miele L., Andriulli A., Niro G. A., Grattagliano I., Morini L., Casella G., Vinci M., Battezzati P. M., Crosignani A., Zuin M., Mattalia A., Calvaruso V., Colombo S., Benedetti A., Marzioni M., Galli A., Marra F., Tarocchi M., Picciotto A., Morisco F., Fabris L., Croce L. S., Tiribelli C., Toniutto P., Strazzabosco M., Ch'ng C. L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Jones S., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Ryder S. D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., Mclindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V. S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Thomas C., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Rolls S. -A., Hynes A., Duggan C., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H. -J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Martin K., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Dali-kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J., Aiba Y., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Kawai Y., Kohn S. -S., Gervais O., Migita K., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Higuchi N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Takikawa H., Ohira H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Carbone M., Cardamone G., Duga S., Gershwin M. E., Seldin M. F., Invernizzi P., Asselta, R, Paraboschi, E, Gerussi, A, Cordell, H, Mells, G, Sandford, R, Jones, D, Nakamura, M, Ueno, K, Hitomi, Y, Kawashima, M, Nishida, N, Tokunaga, K, Nagasaki, M, Tanaka, A, Tang, R, Li, Z, Shi, Y, Liu, X, Xiong, M, Hirschfield, G, Siminovitch, K, Walker, E, Xie, G, Mason, A, Myers, R, Peltekian, K, Ghent, C, Atkinson, E, Juran, B, Lazaridis, K, Lu, Y, Gu, X, Jing, K, Amos, C, Affronti, A, Brunetto, M, Coco, B, Spinzi, G, Elia, G, Ferrari, C, Lleo, A, Muratori, L, Muratori, P, Portincasa, P, Colli, A, Bruno, S, Colloredo, G, Azzaroli, F, Andreone, P, Bragazzi, M, Alvaro, D, Cardinale, V, Cazzagon, N, Rigamonti, C, Floreani, A, Rosina, F, Ciaccio, A, Cristoferi, L, D'Amato, D, Malinverno, F, Mancuso, C, Massironi, S, Milani, C, O'Donnell, S, Ronca, V, Barisani, D, Lampertico, P, Donato, F, Fagiuoli, S, Almasio, P, Giannini, E, Cursaro, C, Colombo, M, Valenti, L, Miele, L, Andriulli, A, Niro, G, Grattagliano, I, Morini, L, Casella, G, Vinci, M, Battezzati, P, Crosignani, A, Zuin, M, Mattalia, A, Calvaruso, V, Colombo, S, Benedetti, A, Marzioni, M, Galli, A, Marra, F, Tarocchi, M, Picciotto, A, Morisco, F, Fabris, L, Croce, L, Tiribelli, C, Toniutto, P, Strazzabosco, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Alexander, G, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Taylor-Robinson, S, Williams, S, Grellier, L, Banim, P, Das, D, Chilton, A, Heneghan, M, Curtis, H, Gess, M, Drake, I, Aldersley, M, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Bathgate, A, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Thorburn, D, Marshall, E, Burroughs, A, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Neuberger, J, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney-Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali-kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordula, J, Aiba, Y, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Kawai, Y, Kohn, S, Gervais, O, Migita, K, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Higuchi, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Takikawa, H, Ohira, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Carbone, M, Cardamone, G, Duga, S, Gershwin, M, Seldin, M, Invernizzi, P, Asselta R., Paraboschi E. M., Gerussi A., Cordell H. J., Mells G. F., Sandford R. N., Jones D. E., Nakamura M., Ueno K., Hitomi Y., Kawashima M., Nishida N., Tokunaga K., Nagasaki M., Tanaka A., Tang R., Li Z., Shi Y., Liu X., Xiong M., Hirschfield G., Siminovitch K. A., Walker E., Xie G., Mason A., Myers R., Peltekian K., Ghent C., Atkinson E., Juran B., Lazaridis K., Lu Y., Gu X., Jing K., Amos C., Affronti A., Brunetto M., Coco B., Spinzi G., Elia G., Ferrari C., Lleo A., Muratori L., Muratori P., Portincasa P., Colli A., Bruno S., Colloredo G., Azzaroli F., Andreone P., Bragazzi M., Alvaro D., Cardinale V., Cazzagon N., Rigamonti C., Floreani A., Rosina F., Ciaccio A., Cristoferi L., D'Amato D., Malinverno F., Mancuso C., Massironi S., Milani C., O'Donnell S. E., Ronca V., Barisani D., Lampertico P., Donato F., Fagiuoli S., Almasio P. L., Giannini E., Cursaro C., Colombo M., Valenti L., Miele L., Andriulli A., Niro G. A., Grattagliano I., Morini L., Casella G., Vinci M., Battezzati P. M., Crosignani A., Zuin M., Mattalia A., Calvaruso V., Colombo S., Benedetti A., Marzioni M., Galli A., Marra F., Tarocchi M., Picciotto A., Morisco F., Fabris L., Croce L. S., Tiribelli C., Toniutto P., Strazzabosco M., Ch'ng C. L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Jones S., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Ryder S. D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., Mclindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V. S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Thomas C., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Rolls S. -A., Hynes A., Duggan C., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H. -J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Martin K., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Dali-kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J., Aiba Y., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Kawai Y., Kohn S. -S., Gervais O., Migita K., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Higuchi N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Takikawa H., Ohira H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Carbone M., Cardamone G., Duga S., Gershwin M. E., Seldin M. F., and Invernizzi P.
Abstract: Background & Aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10–4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10–6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028–1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09–1.26; P = 9.93 × 10–8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10–9; OR, 1.33; 95% CI, 1.21–1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.
Published: 2021

29. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author: Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell H. J., Fryett J. J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S. -S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B. D., Atkinson E. J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M. A. R., Sun D., Jones D. E., Flack S., Spicer A., Mulcahy V. L., Byan J., Han Y., Sandford R. N., Lazaridis K. N., Amos C. I., Hirschfield G. M., Seldin M. F., Invernizzi P., Siminovitch K. A., Ma X., Nakamura M., Mells G. F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P. L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P. M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L. S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G. A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L. A., Overton J. D., Reid J. G., Shuldiner A., Beechert C., Forsythe C., Fuller E. D., Gu Z., Lattari M., Lopez A., Schleicher T. D., Padilla M. S., Toledo K., Widom L., Wolf S. E., Pradhan M., Manoochehri K., Ulloa R. H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E. K., Salerno W., Staples J. C., Jones M. B., Mitnaul L. J., Sturgess R., Healey C., Yeoman A., Gunasekera A. V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J. A., Gorard D. A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M. R., Collins C. E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M. J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I. R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H. M., Ridpath J., Ngatchu T., Bob Grover V. P., Shidrawi R. G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M. A., Curtis H., Matthews H. C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M. I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N. N., Gupta P., Shah A., Evans C. D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S. T., McDonald N., Bathgate A. J., Palmer K., Dillon J. F., Rushbrook S. M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T. J., Ryder S., Collier J., Klass H., Cramp M. E., Sharer N., Aspinall R., Ghosh D., Douds A. C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C. L., Rahman M., Whatley G. C. A., Wesley E., Mandal A., Jain S., Pereira S. P., Wright M., Trivedi P., Gordon F. H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A. D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S. J., Bell A., Wong V. S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell H. J., Fryett J. J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S. -S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B. D., Atkinson E. J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M. A. R., Sun D., Jones D. E., Flack S., Spicer A., Mulcahy V. L., Byan J., Han Y., Sandford R. N., Lazaridis K. N., Amos C. I., Hirschfield G. M., Seldin M. F., Invernizzi P., Siminovitch K. A., Ma X., Nakamura M., Mells G. F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P. L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P. M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L. S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G. A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L. A., Overton J. D., Reid J. G., Shuldiner A., Beechert C., Forsythe C., Fuller E. D., Gu Z., Lattari M., Lopez A., Schleicher T. D., Padilla M. S., Toledo K., Widom L., Wolf S. E., Pradhan M., Manoochehri K., Ulloa R. H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E. K., Salerno W., Staples J. C., Jones M. B., Mitnaul L. J., Sturgess R., Healey C., Yeoman A., Gunasekera A. V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J. A., Gorard D. A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M. R., Collins C. E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M. J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I. R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H. M., Ridpath J., Ngatchu T., Bob Grover V. P., Shidrawi R. G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M. A., Curtis H., Matthews H. C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M. I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N. N., Gupta P., Shah A., Evans C. D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S. T., McDonald N., Bathgate A. J., Palmer K., Dillon J. F., Rushbrook S. M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T. J., Ryder S., Collier J., Klass H., Cramp M. E., Sharer N., Aspinall R., Ghosh D., Douds A. C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C. L., Rahman M., Whatley G. C. A., Wesley E., Mandal A., Jain S., Pereira S. P., Wright M., Trivedi P., Gordon F. H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A. D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S. J., Bell A., Wong V. S., Kia R., Gee I., Keld R., Ransford R., Gotto J., and Millson C.
Abstract: Backgrounds & Aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. Methods: We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. Results: We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. Conclusions: This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China
Published: 2021

30. Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non‐alcoholic fatty liver disease

Author: Eddowes, P. J., McDonald, N., Davies, N., Semple, S. I. K., Kendall, T. J., Hodson, J., Newsome, P. N., Flintham, R. B., Wesolowski, R., Blake, L., Duarte, R. V., Kelly, C. J., Herlihy, A. H., Kelly, M. D., Olliff, S. P., Hübscher, S. G., Fallowfield, J. A., and Hirschfield, G. M.
Published: 2018
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31. Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Author: Montano-Loza, A.J., Ronca, V., Ebadi, M., Hansen, B.E., Hirschfield, G., Elwir, S., Alsaed, M., Milkiewicz, P., Janik, M.K., Marschall, H.U., Burza, M.A., Efe, C., Caliskan, A.R., Harputluoglu, M., Kabacam, G., Terrabuio, D., Onofrio, F.D., Selzner, N., Bonder, A., Pares, A., Llovet, L., Akyildiz, M., Arikan, C., Manns, M.P., Taubert, R., Weber, A.L., Schiano, T.D., Haydel, B., Czubkowski, P., Socha, P., Oldak, N., Akamatsu, N., Tanaka, A., Levy, C., Martin, E.F., Goel, A., Sedki, M., Jankowska, I., Ikegami, T., Rodriguez, M., Sterneck, M., Weiler-Normann, C., Schramm, C., Donato, M.F., Lohse, A., Andrade, R.J., Patwardhan, V.R., Hoek, B. van, Biewenga, M., Kremer, A.E., Ueda, Y., Deneau, M., Pedersen, M., Mayo, M.J., Floreani, A., Burra, P., Secchi, M.F., Beretta-Piccoli, B.T., Sciveres, M., Maggiore, G., Jafri, S.M., Debray, D., Girard, M., Lacaille, F., Lytvyak, E., Mason, A.L., Heneghan, M., Oo, Y.H., and Int Autoimmune Hepatitis Grp IAIHG
Subjects: Adult, Male, Hepatology, liver transplantation, recurrent disease, autoimmune liver disease, graft survival, Mycophenolic Acid, survival, Hepatitis, Autoimmune, Recurrence, Risk Factors, Immunoglobulin G, Humans, Female, Immunosuppressive Agents
Abstract: Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.Methods: We included 736 patients (77% female, mean age 42 +/- 1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT
Published: 2022

32. HLA haplotypes in primary sclerosing cholangitis patients of admixed and non‐European ancestry

Author: Henriksen, E. K. K., Viken, M. K., Wittig, M., Holm, K., Folseraas, T., Mucha, S., Melum, E., Hov, J. R., Lazaridis, K. N., Juran, B. D., Chazouillères, O., Färkkilä, M., Gotthardt, D. N., Invernizzi, P., Carbone, M., Hirschfield, G. M., Rushbrook, S. M., Goode, E., Ponsioen, C. Y., Weersma, R. K., Eksteen, B., Yimam, K. K., Gordon, S. C., Goldberg, D., Yu, L., Bowlus, C. L., Franke, A., Lie, B. A., and Karlsen, T. H.
Published: 2017
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33. Hepatocellular carcinoma for the non-specialist

Author: Kumagi, T, Hiasa, Y, and Hirschfield, G M
Published: 2009

34. Adult liver transplantation: what non-specialists need to know

Author: Hirschfield, G M, Gibbs, P, and Griffiths, W J H
Published: 2009

35. 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

36. 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

37. Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

Author: Pape, Simon, primary, Snijders, Romée J.A.L.M., additional, Gevers, Tom J.G., additional, Chazouilleres, Oliver, additional, Dalekos, George N., additional, Hirschfield, Gideon M., additional, Lenzi, Marco, additional, Trauner, Michael, additional, Manns, Michael P., additional, Vierling, John M., additional, Montano-Loza, Aldo J., additional, Lohse, Ansgar W., additional, Schramm, Christoph, additional, Drenth, Joost P.H., additional, Heneghan, Michael A., additional, Almasio, P., additional, Alvarez, F., additional, Andrade, R., additional, Arikan, C., additional, Assis, D., additional, Bardou-Jacquet, E., additional, Biewenga, M., additional, Cancado, E., additional, Cazzagon, N., additional, Chazouillères, O., additional, Colloredo, G., additional, Cuarterolo, M., additional, Dalekos, G., additional, Debray, D., additional, Robles-Díaz, M., additional, Drenth, J., additional, Dyson, J., additional, Efe, C., additional, Engel, B., additional, Ferri, S., additional, Fontana, R., additional, Gatselis, N., additional, Gerussi, A., additional, Halilbasic, E., additional, Halliday, N., additional, Heneghan, M., additional, Hirschfield, G., additional, van Hoek, B., additional, Hørby Jørgensen, M., additional, Indolfini, G., additional, Iorio, R., additional, Jeong, S., additional, Jones, D., additional, Kelly, D., additional, Kerkar, N., additional, Lacaille, F., additional, Lammert, C., additional, Leggett, B., additional, Lenzi, M., additional, Levy, C., additional, Liberal, R., additional, Lleo, A., additional, Lohse, A., additional, Ines Lopez, S., additional, de Martin, E., additional, McLin, V., additional, Mieli-Vergani, G., additional, Milkiewicz, P., additional, Mohan, N., additional, Muratori, L., additional, Nebbia, G., additional, van Nieuwkerk, C., additional, Oo, Y., additional, Ortega, A., additional, Páres, A., additional, Pop, T., additional, Pratt, D., additional, Purnak, T., additional, Ranucci, G., additional, Rushbrook, S., additional, Schramm, C., additional, Stättermayer, A., additional, Swain, M., additional, Tanaka, A., additional, Taubert, R., additional, Terrabuio, D., additional, Terziroli, B., additional, Trauner, M., additional, Valentino, P., additional, van den Brand, F., additional, Villamil, A., additional, Wahlin, S., additional, Ytting, H., additional, Zachou, K., additional, and Zeniya, M., additional
Published: 2022
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38. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

Author: Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byun, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byun J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M.C., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V.J., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D.J., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J.W., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., and Millson C.
Subjects: PBC
Abstract: It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused.
Published: 2022

39. Expert clinical management of autoimmune hepatitis in the real world

Author: Liberal, R., de Boer, Y. S., Andrade, R. J., Bouma, G., Dalekos, G. N., Floreani, A., Gleeson, D., Hirschfield, G. M., Invernizzi, P., Lenzi, M., Lohse, A. W., Macedo, G., Milkiewicz, P., Terziroli, B., van Hoek, B., Vierling, J. M., and Heneghan, M. A.
Published: 2017
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40. P079 Association of gut microbiota with mucosal inflammation in ulcerative colitis

Author: Quraishi, M.N., Rossiter, A., Chung, B., Beaumont, M., Liaskou, E., Horniblow, R., Beggs, A., Withers, D., Ghosh, S., Tselepis, C., Hirschfield, G., and Iqbal, T.H.
Published: 2017
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41. Editorial: autoimmune hepatitis – identifying options for treatment

Author: Janmohamed, A. and Hirschfield, G. M.
Published: 2016
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42. Reduction and stabilization of bilirubin with obeticholic acid treatment in patients with primary biliary cholangitis

Author: Pares, A, Shiffman, M, Vargas, V, Invernizzi, P, Malecha, E, Liberman, A, Macconell, L, Hirschfield, G, Pares A., Shiffman M., Vargas V., Invernizzi P., Malecha E. S., Liberman A., MacConell L., Hirschfield G., Pares, A, Shiffman, M, Vargas, V, Invernizzi, P, Malecha, E, Liberman, A, Macconell, L, Hirschfield, G, Pares A., Shiffman M., Vargas V., Invernizzi P., Malecha E. S., Liberman A., MacConell L., and Hirschfield G.
Abstract: Background & Aims: Total bilirubin is a predictor of survival in primary biliary cholangitis, with the main elevated component being direct bilirubin. The purpose of this post hoc analysis was to assess the efficacy and safety of obeticholic acid across quartiles of varying baseline levels of direct bilirubin in the phase 3, randomized, placebo-controlled Primary Biliary Cholangitis Obeticholic Acid International Study of Efficacy. Methods: This analysis assessed patients on the basis of their baseline direct bilirubin level (divided by quartile). Biochemistry and safety outcomes were evaluated within each quartile over time. Results: In the quartile with the highest baseline direct bilirubin (>5.47 µmol/L), there was a significant reduction in both direct and total bilirubin at Month 12 compared with placebo. Least squares mean (standard error) change from baseline in direct bilirubin at Month 12 was 4.17 (1.42) µmol/L for placebo, −3.48 (1.63) µmol/L for obeticholic acid 5-10 mg and −3.66 (1.51) µmol/L for obeticholic acid 10 mg (P <.0001, obeticholic acid vs placebo); the corresponding values for total bilirubin at Month 12 were 4.38 (1.55) µmol/L for placebo, −4.53 (1.83) µmol/L for obeticholic acid 5-10 mg and −5.06 (1.64) µmol/L for obeticholic acid 10 mg (P <.0001, obeticholic acid vs placebo). Conclusions: Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at-risk patients.
Published: 2020

43. 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

44. Letter: histology is relevant for risk stratification in primary biliary cholangitis

Author: Carbone, M, D'Amato, D, Hirschfield, G, Jones, D, Mells, G, Carbone M., D'Amato D., Hirschfield G. M., Jones D. E. J., Mells G. F., Carbone, M, D'Amato, D, Hirschfield, G, Jones, D, Mells, G, Carbone M., D'Amato D., Hirschfield G. M., Jones D. E. J., and Mells G. F.
Published: 2020

45. 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

46. Expert consensus criteria and practical recommendations for pbc care in the covid-19 era and beyond

Author: Berenguer, M., primary, Kremer, A.E., additional, Hirschfield, G., additional, Jones, D., additional, Leroy, V., additional, Adekunle, F., additional, and Carbone, M., additional
Published: 2022
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47. A209 EXPERT CONSENSUS CRITERIA AND PRACTICAL RECOMMENDATIONS FOR PBC CARE IN THE COVID-19 ERA AND BEYOND

Author: Hirschfield, G, primary, Berenguer, M, additional, Kremer, A E, additional, Jones, D, additional, Leroy, V, additional, Adekunle, F, additional, and Carbone, M, additional
Published: 2022
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48. A210 HEPATOLITHIASIS IS A FREQUENT AND PROGNOSTIC FINDING IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

Author: Jubran, B, primary, Ismail, M, additional, Stein, M, additional, Little, D H, additional, Hansen, B, additional, Gulamhusein, A, additional, and Hirschfield, G, additional
Published: 2022
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49. P066 Lower serum concentration of sulfated bile acids is associated with Primary Sclerosing Cholangitis Inflammatory Bowel Disease comorbidity and advanced liver fibrosis

Author: Leibovitzh, H, primary, Nayeri, S, additional, Borowski, K, additional, Hernandez-Rocha, C, additional, Lee, S H, additional, Turpin, W, additional, Stempak, J, additional, Sandhu, I, additional, Milgrom, R, additional, Smith, M I, additional, Croitoru, K, additional, Hirschfield, G M, additional, Gulamhusein, A, additional, and Silverberg, M S, additional
Published: 2022
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50. Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes

Author: Cheung, A. C., Lapointe-Shaw, L., Kowgier, M., Meza-Cardona, J., Hirschfield, G. M., Janssen, H. L. A., and Feld, J. J.
Published: 2016
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