Author: "Battezzati, P." / Topic: female - Searchworks@Jio Institute Digital Library Search Results

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18 results on '"Battezzati, P."'

1. A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon

Author: Fattovich, G., Giustina, G., Favarato, S., Ruol, A., Macarri, G., Orlandi, E., Iaquinto, G., Ambrosone, L., Francavilla, A., Pastore, G., Santantonio, M. T., Romagno, D., Bolondi, L., Sofia, S., Marchesini, A., Pisi, E., Mazzella, G., Roda, E., Attaro, L., Chiodo, E., Mori, E., Verucchi, G., Lanzini, A., Salmi, A., Calvi, B., Bozzetti, E., Radaeli, E., Bernasconi, M., Pilleri, G., Bacca, D., Romano, G., Mastrapasqua, G., Cozzolongo, R., Cacopardo, B., Nunnari, A., Blasi, A., Sala, L. O., Minoli, G., Sangiovanni, A., Spinzi, G. C., Colombo, A., Camassa, M., Riva, D., Maggi, G., Boccia, S., Gualandi, G., Nucci, A., Pacini, F., Marino, N., Mazzotta, E., La Mura, A., Pompei, A. G., Casinelli, K., Petrosillo, N., Giacchino, R., Timitilli, A., Spiga, E., Corsetti, M., Menicagli, V., Tucci, A., Bissoli, E., Raimondo, G., Rodino, G., Bellobuono, A., Ideo, G., Colombo, M., Pacchetti, S., Rumi, M. R., Battezzati, P. M., Bruno, S., Podda, M., Zuin, M., Fargion, S., Fiorelli, G., Gellmann, E., Vandelli, C., Ventura, E., Manenti, F., Villa, E., Caporaso, N., Coltorti, M., Morisco, E., Del Vecchio-Blanco, C., di Santolo, S. S., Di Nunzio, S., Ruggiero, G., Zampino, R., Ascione, A., De Luca, M., Galeota-Lanza, A., Aprea, L., Sagnelli, E., Felaco, E. M., Piccinino, E., Ballare, M., Monteverde, A., Tappero, G., Sanna, G., Alberti, A., Bonetti, P., Casarin, C., Diodati, G., Tremolada, E., Naccarato, R., Chiaramonte, M., Floreani, M. R., Almasio, P., Craxi, A., Loiacono, O., Pagliaro, L., Fiaccadori, E., Giuberti, T., Belloni, G., Bernardini, E., Buscarini, L., Sbolli, G., Giudici-Cipriani, A., Marenco, G., Mazzaro, C., Massari, M., Fornaciari, G., Plancher, A., Gasbarrini, G., Grieco, A., Luchetti, R., Rapaccini, G. L., Bombardieri, G., Di Virgilio, D., Bruno, G., Ricci, G. L., Hassan, G., Mari, T., Scalisi, I., Colloredo, G., Frunzio, A., Tabone, M., Costa, C., Rosina, E., Saracco, G., Verme, G., Frezza, M., Urban, E., Capra, E., Casaril, M., Corrocher, R., and Benetti, G. P.
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Hepatitis, Viral, Human, Alpha interferon, Poison control, Chronic viral hepatitis, Interferon alfa, Side effects, Gastroenterology, Autoimmune Diseases, Internal medicine, Medicine, Humans, Adverse effect, Child, Aged, Retrospective Studies, Hepatitis, Hepatology, business.industry, Thyroid disease, Mental Disorders, Infant, Newborn, Infant, Middle Aged, medicine.disease, Recombinant Proteins, Surgery, Bone marrow suppression, Child, Preschool, Chronic Disease, Interferon Type I, Female, business, Viral hepatitis, medicine.drug
Abstract: Aims: The aim of this study was to assess the incidence of fatal, life-threatening side effects and the de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated. Methods: We conducted a retrospective study at 73 Italian centers of 11 241 consecutive patients with chronic vital hepatitis who underwent interferon alfa treatment. Results: Five patients died during interferon therapy due to liver failure ( n =4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes 3 or platelets 3 ). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following de novo non-hepatic disorders: symptomatic thyroid disease ( n =71), impotence ( n =5), systemic autoimmune disease ( n =5), immune-mediated dermatologic disease ( n =14), diabetes mellitus ( n =10), cardiovascular disease ( n =7), psychosis n =10), seizures ( n =4), peripheral neuropathy ( n =3) and hemolytic anemia ( n =2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with de novo non-hepatic morbidity received medium/high doses ( > 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively). Conclusions: Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.
Published: 1996

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

Author: S. Abiru, John F. Dillon, Yasuhiro Miyake, Piero Portincasa, Giancarlo Spinzi, R. Harvey, T. Ngatchu, Agostino Colli, M. Taniai, K. Flahive, Masanori Abe, B. Hoeroldt, S. Holder, Howard Curtis, María Isabel Colombo, C. MacNicol, Gang Xie, Andrew Chilton, H. Hussaini, Cristina Rigamonti, M. Kato, Shintaro Yagi, G. Abouda, D. Tyrer, Chris D. Evans, Christopher I. Amos, K. Koss, Kazuaki Chayama, P. Premchand, K. Migita, Simon Panter, Marco Marzioni, Silvia Colombo, Konstantinos N. Lazaridis, M. Yagura, Ashley Brown, D. Gocher, Domenico Alvaro, K. Murata, Mark Wright, Piero Luigi Almasio, C. Healey, A. Ciaccio, N. Wheatley, Vincenzo Cardinale, T. Delahooke, Chiara Milani, T. Shewan, W. Stableforth, S. Levi, Mark L. Green, James V. Jones, Y. Baird, Aftab Ala, Burroughs Ak, D. Williams, K. Ario, P. Sanghi, Hemant Gupta, P. Southern, L. Farrington, M. Hamilton, Andrew D. Higham, I. Yabuuchi, H. Yatsuhashi, Lorenzo Morini, T. Yamamoto, Douglas Thorburn, M. Carnahan, N. Nishida, Susan Slininger, M. Koga, K. Honda, Annarosa Floreani, Andrew Douglass, K. Netherton, M. Yasunami, Hirohito Tsubouchi, F. Donato, K. Walker, U. Shmueli, Paolo Muratori, Ray Mathew, J. Maiden, E. Dungca, Subramaniam Ramakrishnan, S. Vyas, Helen Sweeting, Subrata Saha, T. Komeda, T. Komatsu, H. J. Lee, Maria Consiglia Bragazzi, T. Komura, C. Thomas, C. Shallcross, C. Duggan, J. Kordula, F. Muscariu, Lourdes Cumlat, Imran Patanwala, Giulia Cardamone, L. Morgan, J. Brighton, Masao Honda, H. Nakamura, David Jones, Raj Srirajaskanthan, M. E. Gershwin, T. Muro, L. Stafford, N. Fukushima, Graham P. Butcher, Andrea Crosignani, George Lipscomb, K. Hirata, Y. Nagaoki, S. Mann, Paul G. Richardson, David A Elphick, M. Mupudzi, Y. Ohara, E. Grieve, Gayle Clifford, Claudio Tiribelli, M. Quinn, G. Van Duyvenvoorde, E. Archer, Tatsuki Ichikawa, J. Maltby, T. Arinaga-Hino, Simon Williams, A. King, Yasuni Nakanuma, H. Doyle, A. Brind, Nora Cazzagon, H. Ota, Daphne D’Amato, K. Hogben, H. Wooldridge, J. Wilkins, Shuichi Kaneko, L. Hankey, Gordon Wood, Andrew Fraser, K. Martin, A. Naqvi, M. Ninkovic, M. Patel, Yoshihiko Maehara, Kapil Kapur, I. Amey, Vincenza Calvaruso, Kenichi Harada, T. Yamashita, James Neuberger, N. Taylor, T. Lee, J. Featherstone, C. Lawlor, K. Seward, Satoshi Yamagiwa, Andrea Galli, L. Tan, Kentaro Kikuchi, K. Furuta, Mark A. Ainsworth, Hiromasa Ohira, Esther Unitt, Yosuke Kawai, N. Lancaster, D. Simpson, R. Shidrawi, I. Salam, A.J. Bell, Pietro Andreone, J. Ishida, Voi Shim Wong, N Fisher, Andrew C. Douds, R. Penn, Matthew Foxton, A. Watson, Andrew Mason, S. Walsh, Hiromi Ishibashi, Daniel M. Forton, Giovanni Casella, H. Takaki, K. Yamauchi, Pietro Lampertico, Osamu Yokosuka, M. Koda, M. Davies, H. Mitchison, P. Gyawali, G. Bird, M. Hughes, L. Jones, C. Hamilton, A. Hynes, R. Galaska, Fabio Marra, Debasish Das, C. Cowley, A. Fouracres, Yasuhiko Sugawara, E. Mita, T. Saoshiro, Akinobu Taketomi, Robert P. Myers, R. Przemioslo, F. Wright, L. Hobson, L. Currie, J. Allison, J. Hails, Noriyo Yamashiki, Massimo Zuin, C. Grimley, Alessio Gerussi, S. Besley, Stefano Duga, A. Piotrowicz, H. Kouno, L. Dali-kemmery, H. Sakai, M. Mizokami, Stefano Fagiuoli, Amy Davis, Pier Maria Battezzati, Masao Nagasaki, Luigi Muratori, A. Mori, S. Desmennu, S. Jones, R. Abrahams, Keith George, F. Makita, J. Brown, D. Gorard, Satoru Joshita, M. Mills, Pierluigi Toniutto, S. Campbell, J. Butterworth, S. Dyer, Filomena Morisco, Norihiro Kokudo, T. Yapp, C. Shorrock, Floriano Rosina, E. Walker, Shinji Uemoto, H. Takahashi, Simon M. Rushbrook, K. Amor, E. Marshall, J. Browning, S. Batham, Luca Fabris, Paul R. Banim, Meenakshi Narain, M. Harada, Dermot Gleeson, N. Hirashima, M. Kikuchi, T. Nikami, Gideon M. Hirschfield, Carlo Ferrari, G. Prasad, O. Chirag, Katsushi Tokunaga, M. Nasseri, Rosanna Asselta, Y. Lu, Ken Shirabe, D. Sirdefield, George F. Mells, K. Sugi, R. Ayres, G. Whatley, A. Singhal, M. Leoni, N. Sivaramakrishnan, T. Harding, Rupert Ransford, Anton V J Gunasekera, C. Mulvaney-Jones, D. Ramanaden, M. Mendall, Muhammad F. Dawwas, Dave Jones, Luca Valenti, Earl J. Williams, Markus Gess, Peter Bramley, A. McNair, E. Hashimoto, P. Townshend, C. Ford, Mario Strazzabosco, Luca Miele, Matthew J Brookes, J. Colley, Mark Wilkinson, H. Dewhurst, Charles Millson, E. Shpuza, Shinji Shimoda, T. Himoto, P. Kitchen, M. Nakamuta, Hiroaki Nishimura, Martin Lombard, Kevork M. Peltekian, M. Pitcher, G. Lim, L. Graves, C. Palmer, S. Lord, S. Katsushima, S. Tripoli, Andrew Austin, N. White, B. Grover, S. Congreave, M. Prince, Rebecca Jones, K. Hirano, A. Shepherd, Y. Mano, Michael A. Heneghan, Richard Sandford, L. O'Donohoe, Marco Carbone, S. A. Rolls, Patrick Goggin, M. L. Cowan, M. Crossey, A. Loftus, K. Young, Mesbah Rahman, Cameron N. Ghent, E. Nambela, M. Xiong, L. Grellier, Sunil Dolwani, Antonio Picciotto, Gill Watts, Alberto Mattalia, Elvezia Maria Paraboschi, J. Orpe, Takeji Umemura, Yuki Hitomi, Fiona H. Gordon, Shotaro Sakisaka, A. Dias, Chin Lye Ch'ng, M. Carter, A. Mandal, Yufang Shi, Takafumi Ichida, N. Masaki, M. Oblak, S. Nagaoka, Kevin Yoong, O. Gervais, Minoru Nakamura, Kazuhiko Nakao, S. Taylor-Robinson, L. Kent, Sushma Saksena, A. Affronti, K. Boulton, R. Ede, H. Pateman, K. Yoshizawa, G. Bray, H. Ebinuma, Yeng Ang, Akio Ido, John Ramage, Richard Sturgess, C. Gray, E. Durant, M. Hayes, A. Saeed, J. Keggans, J. Gitahi, T. Valliani, Edoardo G. Giannini, C. Foale, A. Palegwala, Lory Saveria Crocè, K. Matsushita, S. Shaukat, J. Mclindon, S. Pearson, A. Barnardo, A. Wright, Mirko Tarocchi, R Marley, M. Kent, C. Dickson, A. Gibbins, J. Whiteman, S. Singhal, Richard Aspinall, M. Ito, Laura Cristoferi, Maurizia Rossana Brunetto, J. Booth, A. Bathgate, Morikazu Onji, A. Grant, A. Paton, Y. Aiba, P. Chan, J. Sayer, S. Whalley, T. Mathialahan, J. Gotto, T. Kanda, B. Williams, K. Elliott, P. Raymode, Akinobu Takaki, V. Silvestre, I. Gee, C. Hovell, Graham R. Foster, D. Cotterill, G. Stansfield, Grazia Anna Niro, J. Conder, Yoshiyuki Ueno, A. Shah, Jane Metcalf, S. Hayashi, T. Sato, S. Jain, J. Subhani, Donatella Barisani, A. McKay, Kuniaki Arai, Jeremy Shearman, Torao Tanaka, S. Glenn, S. E. O'Donnell, Federica Malinverno, Denise O'Donnell, R. Casey, N. Sharer, J. Bowles, J. Kendall, Maria Cristina Vinci, Antonio Benedetti, George MacFaul, K. Houghton, Vincenzo Ronca, P. Desousa, B. Holbrook, F. Ali, B. Longhurst, Atsushi Tanaka, Marek Czajkowski, R. Tang, Kazuhide Yamamoto, Y. Watanabe, Graeme J.M. Alexander, R. Cloudsdale, F. Hines, M. Karmo, Brian D. Juran, I. Gooding, Y. Takeyama, J. Fraser, A. Mukhopadhya, Sumihito Tamura, Hajime Takikawa, R. Damant, E. Wilhelmsen, M. Kobayashi, J. Tregonning, V. Lambourne, D. Clement, D. Braim, M. Shimada, S. Sen, Shaun Greer, C. Innes, E. Gunter, C. Brown, H. Klass, A. Komori, Andy Li, H. Fairlamb, N. Ncube, Yoshinori Shimada, M. Harrison, S. Marriott, I. Grattagliano, Savino Bruno, A. Naganuma, Xiangjun Gu, Michael F. Seldin, S. Thornthwaite, Peter R. Mills, Katherine A. Siminovitch, X. Liu, Masataka Seike, J. Curtis, Carmela Cursaro, Z. Li, Mikio Zeniya, K. Warner, B. Bird, Jane Collier, Bridget Gunson, S. Tsuruta, E. Tanqueray, Richard Evans, H. Kamitsukasa, R. Sugimoto, Jeremy Tibble, D. Neal, S. Ducker, Francesco Azzaroli, K. Spurdle, K. Ocker, M. Senju, C. Collins, Y. Nakamura, Matthew E. Cramp, Yuji Soejima, I. Drake, K. Ueno, T. Mannami, Clara Mancuso, M. Kawashima, M. Cox, S. S. Kohn, H. Shibata, Stephen D. Ryder, Christopher Macdonald, J. Ridpath, Stephen P. Pereira, L. March, Barbara Coco, J. Morrison, A. Broad, J. Verheyden, Angelo Andriulli, N. Higuchi, J. Musselwhite, R. Bishop, Gwen Baxter, Richard A. Miller, Guido Colloredo, A. Eastick, I. Rees, Deb Ghosh, L. Winter, Sara Massironi, R. McCorry, Gianfranco Elia, T. Kobata, N. Naeshiro, K. Pollock, J. Gasem, S. Gallagher, K. Jing, S. Misra, B. Shinder, Harriet Gordon, E. Takesaki, J. Sadeghian, S. Tsunematsu, Ana Lleo, M. Aldersley, Elizabeth J. Atkinson, Pietro Invernizzi, Heather J. Cordell, 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.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., 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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, 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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, 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PBC Genetics Study Group, UK-PBC Consortium, Japan PBC-GWAS Consortium, Carbone M, Cardamone G, Duga S, Gershwin ME, Seldin MF, Invernizzi P, and LiveR North
Subjects: Canadian-US PBC Consortium, 0301 basic medicine, Male, Linkage disequilibrium, Genome-wide association study, Disease, PBC, Settore MED/03 - GENETICA MEDICA, Linkage Disequilibrium, 0302 clinical medicine, UK-PBC Consortium, Genotype, Mitochondrial Precursor Protein Import Complex Proteins, Italian PBC Genetics Study Group, Odds Ratio, X-Wide Association Study, Japan PBC-GWAS Consortium, X chromosome, Genetics, Liver Cirrhosis, Biliary, Gastroenterology, Forkhead Transcription Factors, DNA-Binding Proteins, Shal Potassium Channels, 030211 gastroenterology & hepatology, Female, Adult, Monosaccharide Transport Proteins, Superenhancer, Locus (genetics), Single-nucleotide polymorphism, Biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Asian People, Proto-Oncogene Proteins, Endopeptidases, Humans, Cell Lineage, Genetic Predisposition to Disease, Meta-analysi, Genetic association, Chromosomes, Human, X, Gastroenterology & Hepatology, Hepatology, 1103 Clinical Sciences, Meta-analysis, 030104 developmental biology, Genetic Loci, 1114 Paediatrics and Reproductive Medicine, 1109 Neurosciences, Carrier Proteins, Genome-Wide Association Study
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

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

Author: Carla F, Murillo Perez, Alessio, Gerussi, Palak J, Trivedi, Christophe, Corpechot, Adriaan J, van der Meer, Pier, Maria Battezzati, Keith D, Lindor, Frederik, Nevens, Kris V, Kowdley, Tony, Bruns, Nora, Cazzagon, Annarosa, Floreani, Atsushi, Tanaka, Xiong, Ma, Andrew L, Mason, Aliya, Gulamhusein, Cyriel Y, Ponsioen, Marco, Carbone, Ana, Lleo, Marlyn J, Mayo, George N, Dalekos, Nikolaos K, Gatselis, Douglas, Thorburn, Xavier, Verhelst, Albert, Parés, Harry L A, Janssen, Gideon M, Hirschfield, Bettina E, Hansen, Pietro, Invernizzi, Willem J, Lammers, Gastroenterology & Hepatology, Murillo Perez, C, Gerussi, A, Trivedi, P, Corpechot, C, Van Der Meer, A, Maria Battezzati, P, Lindor, K, Nevens, F, Kowdley, K, Bruns, T, Cazzagon, N, Floreani, A, Tanaka, A, Ma, X, Mason, A, Gulamhusein, A, Ponsioen, C, Carbone, M, Lleo, A, Mayo, M, Dalekos, G, Gatselis, N, Thorburn, D, Verhelst, X, Pares, A, Janssen, H, Hirschfield, G, Hansen, B, Invernizzi, P, and Lammers, W
Subjects: Male, Europe, Liver Cirrhosis, Databases, Factual, risk factor, Liver Cirrhosis, Biliary, environmental factor, Graft Survival, Humans, Female, Middle Aged, geography
Abstract: Background and aims The are geographic variations in the incidence and prevalence of primary biliary cholangitis (PBC). The aim was to explore whether clinical outcomes of patients within Western Europe differ according to geographical region. Methods Ursodeoxycholic acid-treated patients from European centers from the Global PBC database diagnosed from 1990 onwards were included. Patients with a time lag > 1 year from diagnosis to start of follow-up were excluded. Differences in baseline characteristics were studied according to North/South and East/West, whereas outcomes (transplant-free survival and decompensation) were studied with center latitude and longitude. Cox regression analyses were adjusted for age, sex, diagnosis year, biochemical markers, and cirrhosis as a time-dependent covariate. Results One thousand eight hundred seventy-eight patients were included, and there were no geographical differences in age or sex, with a mean age of 54 years and 89% female patients. Those in North Europe were more often of a moderately advanced/advanced Rotterdam biochemical stage (28.4%) compared with South Europe (20.6%). Additionally, they exhibited higher median alkaline phosphatase (2.0 ×ULN vs. 1.4 ×ULN) and transaminases. In multivariable analysis, there was a significant interaction between center latitude and longitude for decompensation (P < 0.001) and a trend for transplant-free survival, in which the Northwestern area demonstrated an increased risk for poor outcomes as compared to the reference (Paris). Conclusion We describe geographic variations in outcomes for patients across Europe from specialist centers in the Global PBC Study Group. Further study is important to explore the potential individual, environmental, and healthcare-related factors that may be contributors.
Published: 2023

4. Anti-phospholipid antibody prevalence and association with subclinical atherosclerosis and atherothrombosis in the general population

Author: Carlo Selmi, Simone Aldo Lari, Carlo Alberto Scirè, P. Zermiani, Torsten Matthias, Natasa Isailovic, Sandra Neidhöfer, Pier Maria Battezzati, Damiano Baldassarre, Elena Generali, Massimo Zuin, Maria De Santis, Angela Ceribelli, Selmi, C, De Santis, M, Battezzati, P, Generali, E, Lari, S, Ceribelli, A, Isailovic, N, Zermiani, P, Neidhofer, S, Matthias, T, Scire, C, Baldassarre, D, and Zuin, M
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Heart Diseases, Epidemiology, Population, Cardiovascular event, Serum biomarker, 030204 cardiovascular system & hematology, Random Allocation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Prevalence, Humans, Medicine, 030212 general & internal medicine, Myocardial infarction, education, Stroke, Aged, education.field_of_study, Framingham Risk Score, business.industry, Thrombosis, Odds ratio, Middle Aged, Atherosclerosis, medicine.disease, Cross-Sectional Studies, Italy, Intima-media thickness, Population Surveillance, Antibodies, Antiphospholipid, Female, Cardiology and Cardiovascular Medicine, business, Antiphospholipid antibodie, Body mass index, Biomarkers
Abstract: Background There is no agreement on the prevalence of anti-phospholipid antibodies (aPLs) and the correlation with atherosclerosis and cardiovascular (CV) events in the general population. Methods We performed a cross-sectional study on 1712 randomly enrolled subjects from a Northern Italian city to investigate the presence of aPLs and the association with subclinical atherosclerosis (using the carotid artery intima media thickness measured as inter-adventitia common carotid artery diameters - ICCAD) and retrospectively collected CV factors and events (i.e. acute myocardial infarction, stroke, and peripheral obliterans arterial vasculopathy) using physician-assisted questionnaires. We tested serum IgG, IgM, and IgA anti-cardiolipin, anti-beta2glycoprotein I (aGPI), and anti-phosphatidylserine-prothrombin antibodies. Results Positive aPLs were found in 15.1% of the subjects, with no differences between sex but with higher rates in older subjects. Carotid subclinical atherosclerosis was more frequent in aPL positive subjects; more specifically, aGPI IgA were associated with higher ICCAD average (adjusted beta 0.51, 95% confidence interval (CI)0.17–0.84; p = 0.003). A positive history of CV events was also more frequent in aPL positive subjects (odds ratio (OR) 1.67, 95%CI 1.08–2.54; p = 0.012), particularly peripheral obliterans arterial vasculopathy ( OR 2.02 ; 95%CI 1.14–3.57; p = 0.015). Among subjects with a Framingham risk score >20, and/or diabetes, and/or body mass index >3 5 kg/m 2 , aPL positivity was associated to the highest risk of CV events (OR 2.52, 95%CI 1.24–5.11; p = 0.011). Conclusions APL prevalence in the general population is higher than previously reported. CV events and subclinical atherosclerosis are more frequent in the presence of aPL, particularly when a high CV risk coexists.
Published: 2020
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5. Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase

Author: George N. Dalekos, Harry L.A. Janssen, Albert Parés, Willem J Lammers, Keith D. Lindor, Frederik Nevens, Jordan J. Feld, Maren H. Harms, Pier Maria Battezzati, Henk R. van Buuren, Marlyn J. Mayo, Pietro Invernizzi, Carla F. Murillo Perez, Christophe Corpechot, Annarosa Floreani, Douglas Thorburn, Tony Bruns, Palak J. Trivedi, Kris V. Kowdley, Xavier Verhelst, Ana Lleo, Aliya Gulamhusein, Cyriel Y. Ponsioen, Nikolaos K. Gatselis, Andrew Mason, Bettina E. Hansen, Gideon M. Hirschfield, Adriaan J. van der Meer, Marco Carbone, Murillo Perez, C, Harms, M, Lindor, K, van Buuren, H, Hirschfield, G, Corpechot, C, van der Meer, A, Feld, J, Gulamhusein, A, Lammers, W, Ponsioen, C, Carbone, M, Mason, A, Mayo, M, Invernizzi, P, Battezzati, P, Floreani, A, Lleo, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Thorburn, D, Trivedi, P, Verhelst, X, Parés, A, Janssen, H, Hansen, B, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Gastroenterology & Hepatology
Subjects: Male, medicine.medical_specialty, Cholagogues and Choleretics, Cirrhosis, Bilirubin, Cholangitis, medicine.medical_treatment, Autoimmune hepatitis, Liver transplantation, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, Reference Values, Internal medicine, medicine, Humans, Primary Biliary Cholangiti, Survival rate, Hepatology, business.industry, Hazard ratio, Ursodeoxycholic Acid, Middle Aged, medicine.disease, Alkaline Phosphatase, Prognosis, Survival Rate, chemistry, 030220 oncology & carcinogenesis, Cohort, Alkaline phosphatase, 030211 gastroenterology & hepatology, Female, business, Biomarkers
Abstract: INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels ≤1 × upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP ≤1.67 × ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 × ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin ≤0.6 × ULN and >0.6 × ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 × ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP ≤ 1 × ULN and 86.1% in those with ALP 1.0-1.67 × ULN. DISCUSSION: Attaining bilirubin levels ≤0.6 × ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.
Published: 2020
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6. Measurement of Gamma Glutamyl Transferase to Determine Risk of Liver Transplantation or Death in Patients With Primary Biliary Cholangitis

Author: Keith D. Lindor, Anna Reig, Marco Marzioni, Annarosa Floreani, Sarah Elisabeth O’Donnell, Fabio Marra, Willem J Lammers, Albert Parés, Pier Maria Battezzati, Maria Grazia Valsecchi, Grazia Anna Niro, Benedetta Terziroli Beretta-Piccoli, Harry L.A. Janssen, Adriaan J. van der Meer, Douglas Thorburn, Henk R. van Buuren, Massimo Zuin, Xavier Verhelst, Gideon M. Hirschfield, Andrew Mason, Luca S. Belli, Marlyn J. Mayo, Davide Paolo Bernasconi, Marco Carbone, Frederik Nevens, Alessio Gerussi, Pietro Invernizzi, Nikolaos K. Gatselis, Bettina E. Hansen, Tony Bruns, George N. Dalekos, Christophe Corpechot, Kris V. Kowdley, Nora Cazzagon, Gerussi, A, Bernasconi, D, O'Donnell, S, Lammers, W, Buuren, H, Hirschfield, G, Janssen, H, Corpechot, C, Reig, A, Pares, A, Battezzati, P, Zuin, M, Cazzagon, N, Floreani, A, Nevens, F, Gatselis, N, Dalekos, G, Mayo, M, Thorburn, D, Bruns, T, Mason, A, Verhelst, X, Kowdley, K, van der Meer, A, Niro, G, Beretta-Piccoli, B, Marzioni, M, Belli, L, Marra, F, Valsecchi, M, Lindor, K, Invernizzi, P, Hansen, B, Carbone, M, and Gastroenterology & Hepatology
Subjects: medicine.medical_specialty, medicine.medical_treatment, Liver transplantation, Gastroenterology, digestive system, UDCA, 03 medical and health sciences, 0302 clinical medicine, Cholestasis, MED/12 - GASTROENTEROLOGIA, Internal medicine, Clinical endpoint, medicine, Humans, Autoimmune Liver Disease, Hepatology, Receiver operating characteristic, Liver Cirrhosis, Biliary, business.industry, Proportional hazards model, autoimmune liver disease, Hazard ratio, biomarkers, prediction, gamma-Glutamyltransferase, Biomarker, Prognosis, medicine.disease, Ursodeoxycholic acid, digestive system diseases, Liver Transplantation, 030220 oncology & carcinogenesis, Alkaline phosphatase, Female, 030211 gastroenterology & hepatology, MED/09 - MEDICINA INTERNA, business, Prediction, medicine.drug
Abstract: BACKGROUND & AIMS: Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC). METHODS: We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death. RESULTS: Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r = 0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum levels of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P < .05). Including information on level of GGT increased the prognostic value of the Globe score. CONCLUSIONS: Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatment of metabolic disorders or PBC treatment escalation. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:19 issue:8 pages:1688-+ ispartof: location:United States status: published
Published: 2021

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

Author: Murillo Perez, Fiorella, Hirschfield, GM, Corpechot, C, Floreani, A, Mayo, MJ, van der Meer, Adriaan, Ponsioen, CY, Lammers, Wim, Pares, A, Invernizzi, P, Carbone, M, Battezzati, PM, Nevens, F, Kowdley, KV, Thorburn, D, Mason, AL, Trivedi, PJ, Lindor, KD, Bruns, T, Dalekos, GN, Gatselis, NK, Verhelst, X, Janssen, HL, Hansen, BE, Gulamhusein, A, Grp, GPS, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Gastroenterology & Hepatology, Murillo Perez, C, Hirschfield, G, Corpechot, C, Floreani, A, Mayo, M, van der Meer, A, Ponsioen, C, Lammers, W, Pares, A, Invernizzi, P, Carbone, M, Maria Battezzati, P, Nevens, F, Kowdley, K, Thorburn, D, Mason, A, Trivedi, P, Lindor, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Janssen, H, Hansen, B, and Gulamhusein, A
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Fibrosi, Biopsy, Context (language use), risk stratification, Chronic liver disease, Gastroenterology, Severity of Illness Index, Biomarkers, Pharmacological, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, MED/12 - GASTROENTEROLOGIA, Fibrosis, Predictive Value of Tests, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Primary Biliary Cholangiti, Stage (cooking), Hepatology, medicine.diagnostic_test, business.industry, Liver Cirrhosis, Biliary, Hazard ratio, Ursodeoxycholic Acid, Middle Aged, medicine.disease, Prognosis, Treatment Outcome, Liver, Liver biopsy, Disease Progression, 030211 gastroenterology & hepatology, Female, business, Liver function tests
Abstract: Background: Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. Aim: To assess the utility of baseline fibrosis stage in predicting long‐term outcomes in the context of biochemical risk stratification Methods: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1 year (Toronto/Paris‐II criteria), as well as non‐invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB‐4), for transplant‐free survival was assessed with Cox proportional‐hazards models. Results: There were 1828 patients with baseline liver biopsy. Advanced histologic fi‐ brosis (stage 3/4) was an independent predictor of survival in addition to non‐invasive measures offibrosis with the hazard ratios ranging from 1.59 to 2.73 (P < .001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treat‐ ment response, with a 10‐year survival of 76.0%‐86.6% compared to 94.5%‐95.1% depending on the treatment response criteria used. Poor correlations were observed between non‐invasive measures of fibrosis and histologic fibrosis stage. Conclusion: Assessment of fibrosis stage grants prognostic value beyond biochem‐ ical treatment response at 1 year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.
Published: 2019

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

Author: Keith D. Lindor, Andrew Mason, B.E. Hansen, Maren H. Harms, Cyriel Y. Ponsioen, Gideon M. Hirschfield, Adriaan J. van der Meer, Christophe Corpechot, Willem J Lammers, Albert Parés, Rozanne C de Veer, Kris V. Kowdley, Douglas Thorburn, Palak J. Trivedi, Pier Maria Battezzati, Marlyn J. Mayo, Pietro Invernizzi, Annarosa Floreani, Harry L. A. Janssen, Henk R. van Buuren, Frederik Nevens, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Royal Free Hospital [London, UK], University College of London [London] (UCL), Toronto Western Hospital, Arizona State University [Tempe] (ASU), Mayo Clinic [Rochester], University of Birmingham [Birmingham], Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Universita degli Studi di Padova, University of Texas Southwestern Medical Center, University of Milan, University Hospitals Leuven [Leuven], VU University Medical Center [Amsterdam], University of Alberta, 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, and Gastroenterology & Hepatology
Subjects: Liver Cirrhosis, Male, Cholagogues and Choleretics, Cirrhosis, Databases, Factual, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Trasplantament hepàtic, Liver transplantation, Gastroenterology, hepatobiliary disease, 0302 clinical medicine, Primary biliary cirrhosis, MED/12 - GASTROENTEROLOGIA, Liver Cirrhosis, Biliary, Hepatobiliary disease, Ursodeoxycholic Acid, Middle Aged, Ursodeoxycholic acid, 3. Good health, Survival Rate, Treatment Outcome, Hepatic cirrhosis, 030220 oncology & carcinogenesis, Number needed to treat, 030211 gastroenterology & hepatology, Female, medicine.drug, Numbers Needed To Treat, Adult, medicine.medical_specialty, Cirrosi hepàtica, clinical decision making, liver, 03 medical and health sciences, Internal medicine, medicine, Mortalitat, Humans, Mortality, Survival rate, Aged, Proportional Hazards Models, business.industry, Proportional hazards model, medicine.disease, Alkaline Phosphatase, Liver Transplantation, primary biliary cirrhosis, Chronic Disease, business, Hepatic transplantation
Abstract: ObjectiveThe 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.MethodsThe 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.ResultsWe included 3902 patients with a median follow-up of 7.8 (4.1–12.1) years. The overall HR of UDCA was 0.46 (95% CI 0.40 to 0.52) and the 5-year LT-free survival without UDCA was 81% (95% CI 79 to 82). The NNT to prevent one LT or death within 5 years (NNT5y) was 11 (95% CI 9 to 13). Although the HR of UDCA was similar for patients with and without cirrhosis (0.33 vs 0.31), the NNT5y was 4 (95% CI 3 to 5) and 20 (95% CI 14 to 34), respectively. Among patients with low alkaline phosphatase (ALP) (≤2× the upper limit of normal (ULN)), intermediate ALP (2–4× ULN) and high ALP (>4× ULN), the NNT5y to prevent one LT or death was 26 (95% CI 15 to 70), 11 (95% CI 8 to 17) and 5 (95% CI 4 to 8), respectively.ConclusionThe absolute clinical efficacy of UDCA with respect to LT or death varied with baseline prognostic characteristics, but was high throughout. These findings strongly emphasise the incentive to promptly initiate UDCA treatment in all patients with PBC and may improve patient compliance.
Published: 2019
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9. Effects of Age and Sex of Response to Ursodeoxycholic Acid and Transplant-free Survival in Patients With Primary Biliary Cholangitis

Author: Angela C. Cheung, Kris V. Kowdley, Marlyn J. Mayo, Albert Parés, Konstantinos N. Lazaridis, Ana Lleo, Aliya Gulamhusein, Keith D. Lindor, George N. Dalekos, Tony Bruns, Pietro Invernizzi, Annarosa Floreani, Harry L.A. Janssen, Xavier Verhelst, Willem J Lammers, Carla F. Murillo Perez, Frederik Nevens, Pier Maria Battezzati, Cyriel Y. Ponsioen, Henk R. van Buuren, Christophe Corpechot, Gideon M. Hirschfield, Marco Carbone, Douglas Thorburn, Bettina E. Hansen, Nikolaos K. Gatselis, Raoul Poupon, Andrew Mason, Palak J. Trivedi, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Gastroenterology & Hepatology, Cheung, A, Lammers, W, Murillo Perez, C, van Buuren, H, Gulamhusein, A, Trivedi, P, Lazaridis, K, Ponsioen, C, Floreani, A, Hirschfield, G, Corpechot, C, Mayo, M, Invernizzi, P, Battezzati, P, Parés, A, Nevens, F, Thorburn, D, Mason, A, Carbone, M, Kowdley, K, Bruns, T, Dalekos, G, Gatselis, N, Verhelst, X, Lindor, K, Lleo, A, Poupon, R, Janssen, H, and Hansen, B
Subjects: Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Cholangitis, Cholestatic Liver Disease, Mortality, Risk stratification, Stratified Medicine, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Interquartile range, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Longitudinal Studies, Aged, Retrospective Studies, Hepatology, Proportional hazards model, business.industry, Hazard ratio, Ursodeoxycholic Acid, Gastroenterology, Age Factors, Retrospective cohort study, Odds ratio, Middle Aged, Ursodeoxycholic acid, Liver Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract: BACKGROUND & AIMS: Primary biliary cholangitis (PBC) predominantly affects middle-aged women; there are few data on disease phenotypes and outcomes of PBC in men and younger patients. We investigated whether differences in sex and/or age at the start of ursodeoxycholic acid (UDCA) treatment are associated with response to therapy, based on biochemical markers, or differences in transplant-free survival. METHODS: We performed a longitudinal retrospective study of 4355 adults in the Global PBC Study cohort, collected from 17 centers across Europe and North America. Patients received a diagnosis of PBC from 1961 through 2014. We evaluated the effects of sex and age on response to UDCA treatment (based on GLOBE score) and transplant-free survival using logistic regression and Cox regression analyses, respectively. RESULTS: Male patients were older at the start of treatment (58.3±12.1 years vs 54.3±11.6 years for women; P
Published: 2019

10. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score

Author: Marco Carbone, Alessandra Nardi, Steve Flack, Guido Carpino, Nikoletta Varvaropoulou, Caius Gavrila, Ann Spicer, Jonathan Badrock, Francesca Bernuzzi, Vincenzo Cardinale, Holly F Ainsworth, Michael A Heneghan, Douglas Thorburn, Andrew Bathgate, Rebecca Jones, James M Neuberger, Pier Maria Battezzati, Massimo Zuin, Simon Taylor-Robinson, Maria F Donato, John Kirby, Robert Mitchell-Thain, Annarosa Floreani, Fotios Sampaziotis, Luigi Muratori, Domenico Alvaro, Marco Marzioni, Luca Miele, Fabio Marra, Edoardo Giannini, Eugenio Gaudio, Vincenzo Ronca, Giulia Bonato, Laura Cristoferi, Federica Malinverno, Alessio Gerussi, Deborah D Stocken, Heather J Cordell, Gideon M Hirschfield, Graeme J Alexander, Richard N Sandford, David E Jones, Pietro Invernizzi, George F Mells, Caradog Thomas, Meshbah Rahman, Tom Yapp, Chin Lye Ch'ng, Melanie Harrison, Richard Sturgess, Roman Galaska, Chris Healey, Jessica Whiteman, Marek Czaijkowski, Catherine Gray, Anton Gunasekera, Pranab Gyawli, Purushothaman Premchand, Steven Mann, Keith Elliott, Kapil Kapur, Alan Watson, Graham Foster, Paul Trembling, Javaid Subhani, Rory Harvey, Roger McCorry, Carolyn Adgey, Lucie Hobson, Caroline Mulvaney-Jones, Richard Evans, Thiriloganathan Mathialahan, David Ramanaden, Jaber Gasem, Greta Van Duyvenvoorde, Christopher Shorrock, Katie Seward, Paul Southern, Jeremy Tibble, Ruth Penn, David Gorard, Jane Maiden, Rose Damant, Altaf Palegwala, Susan Jones, Graeme Alexander, George Mells, Richard Sandford, Sunil Dolwani, Martin Prince, Valeria Silvestre, Matthew Foxton, Eleanor Dungca, Harriet Mitchison, Natalie Wheatley, Ian Gooding, Helen Doyle, Mazn Karmo, Melanie Kent, Sushma Saksena, Delyth Braim, Minesh Patel, Susan Lord, Roland Ede, Alison Paton, Andrew Austin, Nicola Lancaster, Joanna Sayer, Andrew Gibbins, Karen Hogben, Chris Hovell, Neil Fisher, Martyn Carter, Konrad Koss, Janine Musselwhite, Florin Muscariu, Andrzej Piotreowicz, Alexandra McKay, Charles Grimley, David Neal, Lai Ting Tan, Guan Lim, Jacqueline Brighton, Carole Foale, Aftab Ala, Athar Saeed, Kerry Flahive, Gordon Wood, Paula Townshend, Chris Ford, Jonathan Brown, Jean Kordula, Jane Bowles, Mark Wilkinson, Caroline Palmer, John Ramage, Harriet Gordon, James Featherstone, Jo Ridpath, Theodore Ngatchu, Sass Levi, Syed Shaukat, Joy Sadeghian, Ray Shidrawi, Bronwen Williams, George Abouda, Sarah Jones, Claire Duggan, Abigail Hynes, Mark Narain, Ian Rees, Imroz Salam, Mary Crossey, Ashley Brown, Carolyn MacNicol, Simon Williams, Elva Wilhelmsen, Paul Banim, Parizade Raymode, Andrew Chilton, Debasish Das, Hye-Jeong Lee, Howard Curtis, Michael Heneghan, Markus Gess, Emma Durant, IM Drake, Rebecca Bishop, Mervyn Davies, Mark Aldersley, Noma Ncube, Alistair McNair, Raj Srirajaskanthan, Sambit Sen, Rebecca Casey, George Bird, Mike Mendall, Caroline Cowley, Adrian Barnardo, Paul Kitchen, Kevin Yoong, Kelly Amore, Dawn Sirdefield, Jacky Orpe, Ray Mathew, George MacFaul, Aruna Wrigth, Amir Shah, Chris Evans, Janie Keggans, Bridget Bird, Gwen Baxter, Subrata Saha, Katharine Pollock, Maggie Hughes, Peter Bramley, Emma Grieve, Karin Young, Andrew Fraser, Ashis Mukhopadhya, Kate Ocker, Peter Mills, Francis Hines, Chris Shallcross, Joy Wilkins, Leonie Grellier, Stewart Campbell, Kirsty Martin, Caron Innes, Alan Shepherd, Simon Rushbrook, Talal Valliani, Robert Przemioslo, Helen Fairlamb, Chris Macdonald, Anne Eastick, Jane Metcalf, Elizabeth Tanqueray, Udi Shmueli, Becky Holbrook, Andrew Davis, Julie Browning, Asifabbas Naqvi, Kirsten Walker, Tom Lee, Juliette Verheyden, Susan Slininger, Stephen D Ryder, Roger Chapman, Jane Collier, Denise O'Donnell, Lizzie Stafford, Kate Williamson, Linda Kent, Howard Klass, Mary Ninkovic, Linda March, Matthew Cramp, Diane Simpson, Christine Dickson, Nicholas Sharer, Maria Hayes, Patrick Goggin, Mary Quinne, Sallyanne Pearson, Barbara Hoeroldt, Linda Jones, Alice Wright, Jonathan Booth, Alison Loftus, George Lipscomb, Hannah Dewhurst, Emma Gunter, Earl Williams, Anna Fouracres, Liz Farrington, Lyn Graves, Hyder Hussaini, Bill Stableforth, Suzie Marriott, Reuben Ayres, Marina Leoni, Andrew Burroughs, Eileen Marshall, David Tyrer, Kate Martin, Martin Lombard, Imran Patanwala, Lola Dali-Kemmery, Victoria Lambourne, Julia Maltby, Samir Vyas, Julie Colley, Bal Shinder, Saket Singhal, Jayne Jones, Marisa Mills, Dermot Gleeson, Mandy Carnahan, Jeff Butterworth, Kerenza Boulton, Natalie Taylor, Keith George, Tim Harding, Julie Tregonning, Andrew Douglass, Carly Brown, Gayle Clifford, Simon Panter, Denise Gocher, Jeremy Shearman, Gary Bray, Maria Hamilton, Graham Butcher, Daniel Forton, John Mclindon, Janette Curtis, Debashis Das, Tracey Shewan, Matthew Cowan, Gregory Whatley, Mariam Nasseri, Bob Grover, Nurani Sivaramakrishnan, Samantha Ducker, Kathryn Houghton, David Jones, Laura Griffiths, Sherill Tripoli, Maxton Pitcher, Ervin Shpuza, Nikki White, Deb Ghosh, Andrew Douds, Marie Green, Matthew Brookes, Lourdes Cumlat, Voi Shim Wong, Karen Warner, Kimberley Netherton, Adtya Mandal, Snjiv Jain, Hemant Gupta, Pradeep Sanghi, Steve Pereira, James Neuberger, Bridget Gunson, Gideon Hirschfield, Reina Teegan Lim, Susan Gallagher, Darren Clement, Alison Brind, Gill Watts, Mcdonald Mupudzi, Mark Wright, Jane Gitahi, Fiona Gordon, Denis Gocher, Esther Unitt, Hilary Pateman, Sally Batham, Toby Delahooke, Allister Grant, Jill Conder, Andrew Higham, Mark Cox, Lynn O'Donohoe, Lynn Currie, Alistair King, Metod Oblak, Carole Collins, Simon Whalley, Marie Quinn, Yolanda Baird, Isobel Amey, Jocelyn Fraser, Andy Li, Donna Cotterill, Andrew Bell, Amit Singhal, Ian Gee, Sandra Greer, Yeng Ang, Rupert Ransford, Joanna Allison, James Gotto, Simon Dyer, Helen Sweeting, Charles Millson, Giancarlo Labbadia, Maria Consiglia Bragazzi, Pietro Andreone, Francesco Azzaroli, Andrea Galli, Mirko Tarocchi, Antonio Gasbarrini, Antonio Grieco, Giuseppe Marrone, Maria Francesca Donato, Luca Valenti, Luca Maroni, Cristina Rigamonti, Antonino Picciotto, Carbone, M, Nardi, A, Flack, S, Carpino, G, Varvaropoulou, N, Gavrila, C, Spicer, A, Badrock, J, Bernuzzi, F, Cardinale, V, Ainsworth, H, Heneghan, M, Thorburn, D, Bathgate, A, Jones, R, Neuberger, J, Battezzati, P, Zuin, M, Taylor-Robinson, S, Donato, M, Kirby, J, Mitchell-Thain, R, Floreani, A, Sampaziotis, F, Muratori, L, Alvaro, D, Marzioni, M, Miele, L, Marra, F, Giannini, E, Gaudio, E, Ronca, V, Bonato, G, Cristoferi, L, Malinverno, F, Gerussi, A, Stocken, D, Cordell, H, Hirschfield, G, Alexander, G, Sandford, R, Jones, D, Invernizzi, P, Mells, G, Thomas, C, Rahman, M, Yapp, T, Lye Ch'ng, C, Harrison, M, Sturgess, R, Galaska, R, Healey, C, Whiteman, J, Czaijkowski, M, Gray, C, Gunasekera, A, Gyawli, P, Premchand, P, Mann, S, Elliott, K, Kapur, K, Watson, A, Foster, G, Trembling, P, Subhani, J, Harvey, R, Mccorry, R, Adgey, C, Hobson, L, Mulvaney-Jones, C, Evans, R, Mathialahan, T, Ramanaden, D, Gasem, J, Van Duyvenvoorde, G, Shorrock, C, Seward, K, Southern, P, Tibble, J, Penn, R, Gorard, D, Maiden, J, Damant, R, Palegwala, A, Jones, S, Dolwani, S, Prince, M, Silvestre, V, Foxton, M, Dungca, E, Mitchison, H, Wheatley, N, Gooding, I, Doyle, H, Karmo, M, Kent, M, Saksena, S, Braim, D, Patel, M, Lord, S, Ede, R, Paton, A, Austin, A, Lancaster, N, Sayer, J, Gibbins, A, Hogben, K, Hovell, C, Fisher, N, Carter, M, Koss, K, Musselwhite, J, Muscariu, F, Piotreowicz, A, Mckay, A, Grimley, C, Neal, D, Ting Tan, L, Lim, G, Brighton, J, Foale, C, Ala, A, Saeed, A, Flahive, K, Wood, G, Townshend, P, Ford, C, Brown, J, Kordula, J, Bowles, J, Wilkinson, M, Palmer, C, Ramage, J, Gordon, H, Featherstone, J, Ridpath, J, Ngatchu, T, Levi, S, Shaukat, S, Sadeghian, J, Shidrawi, R, Williams, B, Abouda, G, Duggan, C, Hynes, A, Narain, M, Rees, I, Salam, I, Crossey, M, Brown, A, Macnicol, C, Williams, S, Wilhelmsen, E, Banim, P, Raymode, P, Chilton, A, Das, D, Lee, H, Curtis, H, Gess, M, Durant, E, Drake, I, Bishop, R, Davies, M, Aldersley, M, Ncube, N, Mcnair, A, Srirajaskanthan, R, Sen, S, Casey, R, Bird, G, Mendall, M, Cowley, C, Barnardo, A, Kitchen, P, Yoong, K, Amore, K, Sirdefield, D, Orpe, J, Mathew, R, Macfaul, G, Wrigth, A, Shah, A, Evans, C, Keggans, J, Bird, B, Baxter, G, Saha, S, Pollock, K, Hughes, M, Bramley, P, Grieve, E, Young, K, Fraser, A, Mukhopadhya, A, Ocker, K, Mills, P, Hines, F, Shallcross, C, Wilkins, J, Grellier, L, Campbell, S, Martin, K, Innes, C, Shepherd, A, Rushbrook, S, Valliani, T, Przemioslo, R, Fairlamb, H, Macdonald, C, Eastick, A, Metcalf, J, Tanqueray, E, Shmueli, U, Holbrook, B, Davis, A, Browning, J, Naqvi, A, Walker, K, Lee, T, Verheyden, J, Slininger, S, Ryder, S, Chapman, R, Collier, J, O'Donnell, D, Stafford, L, Williamson, K, Kent, L, Klass, H, Ninkovic, M, March, L, Cramp, M, Simpson, D, Dickson, C, Sharer, N, Hayes, M, Goggin, P, Quinne, M, Pearson, S, Hoeroldt, B, Jones, L, Wright, A, Booth, J, Loftus, A, Lipscomb, G, Dewhurst, H, Gunter, E, Williams, E, Fouracres, A, Farrington, L, Graves, L, Hussaini, H, Stableforth, B, Marriott, S, Ayres, R, Leoni, M, Burroughs, A, Marshall, E, Tyrer, D, Lombard, M, Patanwala, I, Dali-Kemmery, L, Lambourne, V, Maltby, J, Vyas, S, Colley, J, Shinder, B, Singhal, S, Jones, J, Mills, M, Gleeson, D, Carnahan, M, Butterworth, J, Boulton, K, Taylor, N, George, K, Harding, T, Tregonning, J, Douglass, A, Brown, C, Clifford, G, Panter, S, Gocher, D, Shearman, J, Bray, G, Hamilton, M, Butcher, G, Forton, D, Mclindon, J, Curtis, J, Shewan, T, Cowan, M, Whatley, G, Nasseri, M, Grover, B, Sivaramakrishnan, N, Ducker, S, Houghton, K, Griffiths, L, Tripoli, S, Pitcher, M, Shpuza, E, White, N, Ghosh, D, Douds, A, Green, M, Brookes, M, Cumlat, L, Wong, V, Warner, K, Netherton, K, Mandal, A, Jain, S, Gupta, H, Sanghi, P, Pereira, S, Gunson, B, Lim, R, Gallagher, S, Clement, D, Brind, A, Watts, G, Mupudzi, M, Wright, M, Gitahi, J, Gordon, F, Unitt, E, Pateman, H, Batham, S, Delahooke, T, Grant, A, Conder, J, Higham, A, Cox, M, O'Donohoe, L, Currie, L, King, A, Oblak, M, Collins, C, Whalley, S, Quinn, M, Baird, Y, Amey, I, Fraser, J, Li, A, Cotterill, D, Bell, A, Singhal, A, Gee, I, Greer, S, Ang, Y, Ransford, R, Allison, J, Gotto, J, Dyer, S, Sweeting, H, Millson, C, Labbadia, G, Bragazzi, M, Andreone, P, Azzaroli, F, Galli, A, Tarocchi, M, Gasbarrini, A, Grieco, A, Marrone, G, Valenti, L, Maroni, L, Rigamonti, C, Picciotto, A, Sampaziotis, Fotios [0000-0003-0812-7586], Sandford, Richard [0000-0002-7437-0560], Apollo - University of Cambridge Repository, Carbone, Marco, Nardi, Alessandra, Flack, Steve, Carpino, Guido, Varvaropoulou, Nikoletta, Gavrila, Caiu, Spicer, Ann, Badrock, Jonathan, Bernuzzi, Francesca, Cardinale, Vincenzo, Ainsworth, Holly F, Heneghan, Michael A, Thorburn, Dougla, Bathgate, Andrew, Jones, Rebecca, Neuberger, James M, Battezzati, Pier Maria, Zuin, Massimo, Taylor-Robinson, Simon, Donato, Maria F, Kirby, John, Mitchell-Thain, Robert, Floreani, Annarosa, Sampaziotis, Fotio, Muratori, Luigi, Alvaro, Domenico, Marzioni, Marco, Miele, Luca, Marra, Fabio, Giannini, Edoardo, Gaudio, Eugenio, Ronca, Vincenzo, Bonato, Giulia, Cristoferi, Laura, Malinverno, Federica, Gerussi, Alessio, Stocken, Deborah D, Cordell, Heather J, Hirschfield, Gideon M, Alexander, Graeme J, Sandford, Richard N, Jones, David E, Invernizzi, Pietro, Mells, George F, Thomas, Caradog, Rahman, Meshbah, Yapp, Tom, Lye Ch'ng, Chin, Harrison, Melanie, Sturgess, Richard, Galaska, Roman, Healey, Chri, Whiteman, Jessica, Czaijkowski, Marek, Gray, Catherine, Gunasekera, Anton, Gyawli, Pranab, Premchand, Purushothaman, Mann, Steven, Elliott, Keith, Kapur, Kapil, Watson, Alan, Foster, Graham, Trembling, Paul, Subhani, Javaid, Harvey, Rory, McCorry, Roger, Adgey, Carolyn, Hobson, Lucie, Mulvaney-Jones, Caroline, Evans, Richard, Mathialahan, Thiriloganathan, Ramanaden, David, Gasem, Jaber, Van Duyvenvoorde, Greta, Shorrock, Christopher, Seward, Katie, Southern, Paul, Tibble, Jeremy, Penn, Ruth, Gorard, David, Maiden, Jane, Damant, Rose, Palegwala, Altaf, Jones, Susan, Alexander, Graeme, Mells, George, Sandford, Richard, Dolwani, Sunil, Prince, Martin, Silvestre, Valeria, Foxton, Matthew, Dungca, Eleanor, Mitchison, Harriet, Wheatley, Natalie, Gooding, Ian, Doyle, Helen, Karmo, Mazn, Kent, Melanie, Saksena, Sushma, Braim, Delyth, Patel, Minesh, Lord, Susan, Ede, Roland, Paton, Alison, Austin, Andrew, Lancaster, Nicola, Sayer, Joanna, Gibbins, Andrew, Hogben, Karen, Hovell, Chri, Fisher, Neil, Carter, Martyn, Koss, Konrad, Musselwhite, Janine, Muscariu, Florin, Piotreowicz, Andrzej, McKay, Alexandra, Grimley, Charle, Neal, David, Ting Tan, Lai, Lim, Guan, Brighton, Jacqueline, Foale, Carole, Ala, Aftab, Saeed, Athar, Flahive, Kerry, Wood, Gordon, Townshend, Paula, Ford, Chri, Brown, Jonathan, Kordula, Jean, Bowles, Jane, Wilkinson, Mark, Palmer, Caroline, Ramage, John, Gordon, Harriet, Featherstone, Jame, Ridpath, Jo, Ngatchu, Theodore, Levi, Sa, Shaukat, Syed, Sadeghian, Joy, Shidrawi, Ray, Williams, Bronwen, Abouda, George, Jones, Sarah, Duggan, Claire, Hynes, Abigail, Narain, Mark, Rees, Ian, Salam, Imroz, Crossey, Mary, Brown, Ashley, MacNicol, Carolyn, Williams, Simon, Wilhelmsen, Elva, Banim, Paul, Raymode, Parizade, Chilton, Andrew, Das, Debasish, Lee, Hye-Jeong, Curtis, Howard, Heneghan, Michael, Gess, Marku, Durant, Emma, Drake, I.M., Bishop, Rebecca, Davies, Mervyn, Aldersley, Mark, Ncube, Noma, McNair, Alistair, Srirajaskanthan, Raj, Sen, Sambit, Casey, Rebecca, Bird, George, Mendall, Mike, Cowley, Caroline, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Amore, Kelly, Sirdefield, Dawn, Orpe, Jacky, Mathew, Ray, MacFaul, George, Wrigth, Aruna, Shah, Amir, Evans, Chri, Keggans, Janie, Bird, Bridget, Baxter, Gwen, Saha, Subrata, Pollock, Katharine, Hughes, Maggie, Bramley, Peter, Grieve, Emma, Young, Karin, Fraser, Andrew, Mukhopadhya, Ashi, Ocker, Kate, Mills, Peter, Hines, Franci, Shallcross, Chri, Wilkins, Joy, Grellier, Leonie, Campbell, Stewart, Martin, Kirsty, Innes, Caron, Shepherd, Alan, Rushbrook, Simon, Valliani, Talal, Przemioslo, Robert, Fairlamb, Helen, Macdonald, Chri, Eastick, Anne, Metcalf, Jane, Tanqueray, Elizabeth, Shmueli, Udi, Holbrook, Becky, Davis, Andrew, Browning, Julie, Naqvi, Asifabba, Walker, Kirsten, Lee, Tom, Verheyden, Juliette, Slininger, Susan, Ryder, Stephen D, Chapman, Roger, Collier, Jane, O'Donnell, Denise, Stafford, Lizzie, Williamson, Kate, Kent, Linda, Klass, Howard, Ninkovic, Mary, March, Linda, Cramp, Matthew, Simpson, Diane, Dickson, Christine, Sharer, Nichola, Hayes, Maria, Goggin, Patrick, Quinne, Mary, Pearson, Sallyanne, Hoeroldt, Barbara, Jones, Linda, Wright, Alice, Booth, Jonathan, Loftus, Alison, Lipscomb, George, Dewhurst, Hannah, Gunter, Emma, Williams, Earl, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Hussaini, Hyder, Stableforth, Bill, Marriott, Suzie, Ayres, Reuben, Leoni, Marina, Burroughs, Andrew, Marshall, Eileen, Tyrer, David, Martin, Kate, Lombard, Martin, Patanwala, Imran, Dali-Kemmery, Lola, Lambourne, Victoria, Maltby, Julia, Vyas, Samir, Colley, Julie, Shinder, Bal, Singhal, Saket, Jones, Jayne, Mills, Marisa, Gleeson, Dermot, Carnahan, Mandy, Butterworth, Jeff, Boulton, Kerenza, Taylor, Natalie, George, Keith, Harding, Tim, Tregonning, Julie, Douglass, Andrew, Brown, Carly, Clifford, Gayle, Panter, Simon, Gocher, Denise, Shearman, Jeremy, Bray, Gary, Hamilton, Maria, Butcher, Graham, Forton, Daniel, Mclindon, John, Curtis, Janette, Das, Debashi, Shewan, Tracey, Cowan, Matthew, Whatley, Gregory, Nasseri, Mariam, Grover, Bob, Sivaramakrishnan, Nurani, Ducker, Samantha, Houghton, Kathryn, Jones, David, Griffiths, Laura, Tripoli, Sherill, Pitcher, Maxton, Shpuza, Ervin, White, Nikki, Ghosh, Deb, Douds, Andrew, Green, Marie, Brookes, Matthew, Cumlat, Lourde, Wong, Voi Shim, Warner, Karen, Netherton, Kimberley, Mandal, Adtya, Jain, Snjiv, Gupta, Hemant, Sanghi, Pradeep, Pereira, Steve, Neuberger, Jame, Gunson, Bridget, Hirschfield, Gideon, Lim, Reina Teegan, Gallagher, Susan, Clement, Darren, Brind, Alison, Watts, Gill, Mupudzi, Mcdonald, Wright, Mark, Gitahi, Jane, Gordon, Fiona, Gocher, Deni, Unitt, Esther, Pateman, Hilary, Batham, Sally, Delahooke, Toby, Grant, Allister, Conder, Jill, Higham, Andrew, Cox, Mark, O'Donohoe, Lynn, Currie, Lynn, King, Alistair, Oblak, Metod, Collins, Carole, Whalley, Simon, Quinn, Marie, Baird, Yolanda, Amey, Isobel, Fraser, Jocelyn, Li, Andy, Cotterill, Donna, Bell, Andrew, Singhal, Amit, Gee, Ian, Greer, Sandra, Ang, Yeng, Ransford, Rupert, Allison, Joanna, Gotto, Jame, Dyer, Simon, Sweeting, Helen, Millson, Charle, Labbadia, Giancarlo, Bragazzi, Maria Consiglia, Andreone, Pietro, Azzaroli, Francesco, Galli, Andrea, Tarocchi, Mirko, Gasbarrini, Antonio, Grieco, Antonio, Marrone, Giuseppe, Donato, Maria Francesca, Valenti, Luca, Maroni, Luca, Rigamonti, Cristina, Picciotto, Antonino, and Medical Research Council (MRC)
Subjects: Male, Cholagogues and Choleretics, Cirrhosis, medicine.medical_treatment, PROGRESSION, Liver transplantation, PHENOTYPE, Gastroenterology, UDCA, 0302 clinical medicine, Primary biliary cirrhosis, Risk Factors, Medicine, Age of Onset, CIRRHOSIS, TREE, OUTCOMES, Settore MED/12 - Gastroenterologia, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Area under the curve, URSODIOL, Middle Aged, Ursodeoxycholic acid, Treatment Outcome, Primary biliary cholangitis, ursodeoxycholic acid, 030220 oncology & carcinogenesis, Liver biopsy, Area Under Curve, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, CONTROLLED-TRIAL, Hepatology, Decision Support Techniques, Time-to-Treatment, Biliary injury, 03 medical and health sciences, Internal medicine, Humans, Transaminases, Science & Technology, Gastroenterology & Hepatology, Italian PBC Study Group and the UK–PBC Consortium, business.industry, Bilirubin, medicine.disease, Alkaline Phosphatase, ROC Curve, CELLS, Linear Models, business
Abstract: Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1Â·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p
Published: 2018
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11. Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history

Author: Kris V. Kowdley, George N. Dalekos, Pietro Invernizzi, Carla F. Murillo Perez, Gideon M. Hirschfield, Frederik Nevens, Douglas Thorburn, Marco Carbone, Xavier Verhelst, Cyriel Y. Ponsioen, Christophe Corpechot, Willem J Lammers, Aliya Gulamhusein, Jorn C Goet, Harry L.A. Janssen, Tony Bruns, Palak J. Trivedi, Annarosa Floreani, Pier Maria Battezzati, Kalliopi Zachou, Albert Parés, Marlyn J. Mayo, Henk R. van Buuren, Nicholas F. LaRusso, Bettina E. Hansen, Keith D. Lindor, Raoul Poupon, Andrew Mason, Gastroenterology & Hepatology, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Murillo Perez, C, Goet, J, Lammers, W, Gulamhusein, A, van Buuren, H, Ponsioen, C, Carbone, M, Mason, A, Corpechot, C, Invernizzi, P, Mayo, M, Battezzati, P, Floreani, A, Pares, A, Nevens, F, Kowdley, K, Bruns, T, Dalekos, G, Thorburn, D, Hirschfield, G, Larusso, N, Lindor, K, Zachou, K, Poupon, R, Trivedi, P, Verhelst, X, Janssen, H, and Hansen, B
Subjects: Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Databases, Factual, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver Function Tests, Retrospective Studie, Internal medicine, medicine, Humans, Decompensation, diagnosis year, Cholagogues and Choleretic, Survival analysis, Aged, Retrospective Studies, Hepatology, medicine.diagnostic_test, Liver Function Test, business.industry, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Autoimmune liver disease, age at diagnosis, disease severity, epidemiology, Retrospective cohort study, Middle Aged, Survival Analysis, Ursodeoxycholic acid, Europe, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, North America, 030211 gastroenterology & hepatology, Female, Survival Analysi, Liver function, Liver function tests, business, Human, medicine.drug
Abstract: Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235). Age at diagnosis, disease stage, response to ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9 ± 10.1 years in the 1970s to 57.0 ± 12.1 years from 2010 onward (P < 0.001). The female to male ratio (9:1) and antimitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort; P < 0.001). Conclusion: In recent decades, a pattern of primary biliary cholangitis presentation consistent with an older age at diagnosis alongside reduced disease severity has been noted; the observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. (Hepatology 2018;67:1920-1930).
Published: 2018
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12. Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome

Author: Kris V. Kowdley, Keith D. Lindor, George N. Dalekos, Bettina E. Hansen, Douglas Thorburn, Jorn Goet, Christophe Corpechot, Maren H. Harms, Cyriel Y. Ponsioen, Harry L.A. Janssen, Pietro Invernizzi, Annarosa Floreani, Tony Bruns, Albert Parés, Willem J Lammers, Xavier Verhelst, Andrew Mason, Gideon M. Hirschfield, Pier Maria Battezzati, Frederik Nevens, Henk R. van Buuren, Marlyn J. Mayo, Gastroenterology & Hepatology, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Harms, M, Lammers, W, Thorburn, D, Corpechot, C, Invernizzi, P, Janssen, H, Battezzati, P, Nevens, F, Lindor, K, Floreani, A, Ponsioen, C, Mayo, M, Dalekos, G, Bruns, T, Parés, A, Mason, A, Verhelst, X, Kowdley, K, Goet, J, Hirschfield, G, Hansen, B, and Van Buuren, H
Subjects: Adult, Male, medicine.medical_specialty, Cholagogues and Choleretics, Kaplan-Meier Estimate, Hepatic Complication, Esophageal and Gastric Varices, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, Risk Factors, Internal medicine, medicine, Humans, Aspartate Aminotransferases, Population Growth, Aged, Proportional Hazards Models, Hepatology, Proportional hazards model, business.industry, Time trends, Liver Cirrhosis, Biliary, Platelet Count, Incidence (epidemiology), Incidence, Disease progression, Ursodeoxycholic Acid, Ascites, Middle Aged, Prognosis, Ursodeoxycholic acid, Europe, 030220 oncology & carcinogenesis, Hepatic Encephalopathy, North America, Disease Progression, 030211 gastroenterology & hepatology, Female, business, Gastrointestinal Hemorrhage, medicine.drug, Cohort study
Abstract: Objectives: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. Methods: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. Results: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. Conclusions: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.
Published: 2017

13. Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis

Author: Vanila Pozzoli, Francesca Bernuzzi, Ana Lleo, Massimo Zuin, Andrea Crosignani, Pietro Invernizzi, Chiara Raggi, Pier Maria Battezzati, Monica Bignotto, P. Zermiani, Mauro Podda, Invernizzi, P, Bernuzzi, F, Lleo, A, Pozzoli, V, Bignotto, M, Zermiani, P, Crosignani, A, Battezzati, P, Zuin, M, Podda, M, and Raggi, C
Subjects: Liver Cirrhosis, Adult, medicine.medical_specialty, Telomerase, Primary biliary cirrhosi, Cirrhosis, Liver Cirrhosi, Population, Peripheral blood mononuclear cell, Telomere dysfunction, Primary biliary cirrhosis, Telomere Homeostasis, Internal medicine, Autoimmune disease, Humans, Medicine, education, Cellular Senescence, Telomere Shortening, Aged, education.field_of_study, Hepatology, Liver Cirrhosis, Biliary, business.industry, Gastroenterology, Hepatitis C, Chronic, Middle Aged, Telomere, medicine.disease, Telomere Homeostasi, Cell Aging, Case-Control Studies, Immunology, Leukocytes, Mononuclear, Female, Case-Control Studie, business, Human
Abstract: Background: Chromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence. Aim: To evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. Study design: In this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured. Results: Telomere length and telomerase activity did not differ between cases (5.9±1.5kb) and controls (6.2±1.4kb, pc=0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6±0.9 OD vs. 1.5±3.7 OD, p=0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis. Conclusion: Our data strongly support the telomere hypothesis of human cirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of human cirrhosis in a selected population of patients. © 2013 Editrice Gastroenterologica Italiana S.r.l
Published: 2014
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14. Evolving Trends in Female to Male Incidence and Male Mortality of Primary Biliary Cholangitis

Author: Emanuela Morenghi, Ana Lleo, Pietro Invernizzi, Peter Uhd Jepsen, Ian R. Mackay, Marco Carbone, Pier Maria Battezzati, Luca Moroni, Mauro Podda, M. Eric Gershwin, Lleo, A, Jepsen, P, Morenghi, E, Carbone, M, Moroni, L, Battezzati, P, Podda, M, Mackay, I, Gershwin, M, and Invernizzi, P
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pediatrics, Denmark, Population, prevalence, Prevalence, Article, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, cell immune-response, medicine, follow-up, Journal Article, Humans, Registries, education, Survival analysis, changing nomenclature, Sex Characteristics, education.field_of_study, Multidisciplinary, Liver Cirrhosis, Biliary, Proportional hazards model, business.industry, Incidence, Incidence (epidemiology), natural-history, Survival Analysis, pbc, digestive system diseases, ursodeoxycholic acid, 030104 developmental biology, Italy, primary sclerosing cholangiti, Regression Analysis, Female, 030211 gastroenterology & hepatology, epidemiology, business, Sex ratio, Demography, Sex characteristics, cirrhosi
Abstract: Primary biliary cholangitis (PBC) has been regarded as female-predominant without evidence of gender difference in survival. We aimed to compare the overall survival, incidence and prevalence of PBC in two well defined population-based studies over a recent decade, considering also sex ratios and mortality. We have taken advantage of population-wide records, during 2000–2009, in Lombardia, Northern Italy and Denmark. We focused on the incident cases of PBC, including gender and outcome, among 9.7 million inhabitants of Lombardia and 5.5 million of Denmark. In Lombardia there were 2,970 PBC cases with a female:male ratio of 2.3:1. The age/sex-adjusted annual incidence of PBC was 16.7 per million. Point prevalence was 160 per million on January 1st 2009. In Denmark there were 722 cases of incident PBC, female:male ratio was 4.2:1 and the annual incidence was 11.4 per million, a point prevalence of 115 per million in 2009. Cox regression multivariate analysis identified male sex as an independent predictor of all-cause mortality in both Italian (HR 2.36) and Danish population (HR 3.04). Our data indicate for PBC a sex ratio significantly lower than previously cited, a reversal of the usual latitudinal difference in prevalence and a surprisingly higher overall mortality for male patients.
Published: 2016
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15. Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study

Author: Bettina E. Hansen, Keith D. Lindor, Palak J. Trivedi, Harry L.A. Janssen, Annarosa Floreani, Raoul Poupon, Cyriel Y. Ponsioen, Andrew K. Burroughs, Willem J Lammers, Andrew Mason, Pier Maria Battezzati, Albert Parés, Gideon M. Hirschfield, Llorenç Caballería, Christophe Corpechot, Frederik Nevens, Henk R. van Buuren, Marlyn J. Mayo, Kris V. Kowdley, Ana Lleo, Pietro Invernizzi, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Other departments, Gastroenterology & Hepatology, Trivedi, P, Lammers, W, Van Buuren, H, Parés, A, Floreani, A, Janssen, H, Invernizzi, P, Battezzati, P, Ponsioen, C, Corpechot, C, Poupon, R, Mayo, M, Burroughs, A, Nevens, F, Mason, A, Kowdley, K, Lleo, A, Caballeria, L, Lindor, K, Hansen, B, and Hirschfield, G
Subjects: Oncology, Liver Cirrhosis, Male, PRIMARY BILIARY CIRRHOSIS, Sex Factor, Kaplan-Meier Estimate, Logistic regression, Gastroenterology, AUTOIMMUNE LIVER DISEASE, CHOLESTATIC LIVER DISEASES, Aspartate Aminotransferases, Carcinoma, Hepatocellular, Europe, Female, Humans, Liver Cirrhosis, Biliary, Liver Neoplasms, Logistic Models, North America, Proportional Hazards Models, Risk, Risk Factors, Sex Factors, Thrombocytopenia, Ursodeoxycholic Acid, 0302 clinical medicine, Primary biliary cirrhosis, MED/12 - GASTROENTEROLOGIA, Critical event, Biliary, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Risk stratification, 030211 gastroenterology & hepatology, Human, medicine.medical_specialty, Logistic Model, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, In patient, business.industry, Proportional hazards model, Risk Factor, Carcinoma, Aspartate Aminotransferase, Hepatocellular, medicine.disease, digestive system diseases, Proportional Hazards Model, business
Abstract: Objective Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC. Design Risk factor analysis was performed in over 15 centres from North America and Europe spanning >40 years observation period using Cox proportional hazards assumptions, logistic regression, and Kaplan-Meier estimates. Results Of 4565 patients with PBC 123 developed HCC, yielding an incidence rate (IR) of 3.4 cases/1000 patient-years. HCC was significantly more common in men (p
Published: 2016

16. Development and Validation of a Scoring System to Predict Outcomes of Patients with Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy

Author: Keith D. Lindor, Pier Maria Battezzati, Maren H. Harms, Cyriel Y. Ponsioen, Gideon M. Hirschfield, Harry La Janssen, Andrew K. Burroughs, Llorenç Caballería, Kris V. Kowdley, Henk R. van Buuren, Ana Lleo, Marlyn J. Mayo, Teru Kumagi, Frederik Nevens, Annarosa Floreani, Pietro Invernizzi, Albert Parés, Christophe Corpechot, Palak J. Trivedi, Angela M. Cheung, Raoul Poupon, Andrew Mason, Bettina E. Hansen, Willem J Lammers, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Surgery, Gastroenterology & Hepatology, Public Health, Lammers, W, Hirschfield, G, Corpechot, C, Nevens, F, Lindor, K, Janssen, H, Floreani, A, Ponsioen, C, Mayo, M, Invernizzi, P, Battezzati, P, Parés, A, Burroughs, A, Mason, A, Kowdley, K, Kumagi, T, Harms, M, Trivedi, P, Poupon, R, Cheung, A, Lleo, A, Caballeria, L, Hansen, B, and Van Buuren, H
Subjects: Liver Cirrhosis, Male, Cholagogues and Choleretics, Time Factors, Predictive Value of Test, Sex Factor, Kaplan-Meier Estimate, Decision Support Technique, Primary biliary cirrhosis, MED/12 - GASTROENTEROLOGIA, Risk Factors, Medicine, Age Factor, Cholagogues and Choleretic, Autoimmune Liver Disease, Multivariate Analysi, education.field_of_study, Framingham Risk Score, Cholestasis, Liver Cirrhosis, Biliary, Medicine (all), Hazard ratio, Biliary, Ursodeoxycholic Acid, Age Factors, Gastroenterology, Predictive Factor, Prognosis, Adult, Aged, Biomarkers, Disease Progression, Disease-Free Survival, Europe, Female, Humans, Liver Transplantation, Middle Aged, Multivariate Analysis, North America, Predictive Value of Tests, Proportional Hazards Models, Reproducibility of Results, Risk Assessment, Sex Factors, Treatment Outcome, Decision Support Techniques, Ursodeoxycholic acid, Cholestasi, Predictive value of tests, Human, medicine.drug, medicine.medical_specialty, Time Factor, Prognosi, Population, Reproducibility of Result, Internal medicine, education, Hepatology, business.industry, Proportional hazards model, Risk Factor, Biomarker, medicine.disease, Confidence interval, Surgery, Proportional Hazards Model, business
Abstract: BACKGROUND & AIMS: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC. METHODS: We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n = 2488 [60%]) and validation cohorts (n = 1631 [40%]). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 year of ursodeoxycholic acid therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria. RESULTS: Age (hazard ratio = 1.05; 95% confidence interval [CI]: 1.04-1.06; P 0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P
Published: 2015

17. Levels of Alkaline Phosphatase and Bilirubin Are Surrogate End Points of Outcomes of Patients With Primary Biliary Cirrhosis: An International Follow-up Study

Author: Gideon M. Hirschfield, Nora Cazzagon, Raoul Poupon, Andrew K. Burroughs, Willem J Lammers, Henk R. van Buuren, Andrew Mason, I. Franceschet, Pushpjeet Kanwar, Frederik Nevens, Teru Kumagi, Angela M. Cheung, Annarosa Floreani, Marlyn J. Mayo, Bettina E. Hansen, Cyriel Y. Ponsioen, Harry L.A. Janssen, Christophe Corpechot, Albert Parés, Kris V. Kowdley, Ana Lleo, Keith D. Lindor, Pietro Invernizzi, Kirsten Boonstra, Palak J. Trivedi, Pier Maria Battezzati, Mohamad Imam, G. Pieri, Llorenç Caballería, Gastroenterology & Hepatology, Lammers, W, Van Buuren, H, Hirschfield, G, Janssen, H, Invernizzi, P, Mason, A, Ponsioen, C, Floreani, A, Corpechot, C, Mayo, M, Battezzati, P, Parés, A, Nevens, F, Burroughs, A, Kowdley, K, Trivedi, P, Kumagi, T, Cheung, A, Lleo, A, Imam, M, Boonstra, K, Cazzagon, N, Franceschet, I, Poupon, R, Caballeria, L, Pieri, G, Kanwar, P, Lindor, K, Hansen, B, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Other departments
Subjects: Male, Cholagogues and Choleretics, medicine.medical_treatment, Predictive Value of Test, Liver transplantation, New Therapies, Gastroenterology, chemistry.chemical_compound, Primary biliary cirrhosis, Risk Factors, MED/12 - GASTROENTEROLOGIA, Cholagogues and Choleretic, Autoimmune Liver Disease, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Hazard ratio, Middle Aged, Prognosis, Predictive value of tests, Alkaline phosphatase, Education, Medical, Continuing, Female, Survival Analysi, Human, Cohort study, Adult, medicine.medical_specialty, Prognosi, Bilirubin, Autoimmune Liver Disease, Response To Treatment, Biomarker, New Therapies, Follow-Up Studie, Predictive Value of Tests, Internal medicine, medicine, Humans, Survival analysis, Aged, New Therapie, Hepatology, business.industry, Risk Factor, Response To Treatment, Biomarker, Alkaline Phosphatase, medicine.disease, Survival Analysis, Liver Transplantation, Surgery, chemistry, business, Biomarkers, Follow-Up Studies
Abstract: BACKGROUND & AIMS: Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points. METHODS: We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies. Levels of alkaline phosphatase and bilirubin were analyzed in different settings and sub-populations at different time points relative to the clinical end point (liver transplantation or death). RESULTS: Of the 4845 patients, 1118 reached a clinical end point. The median follow-up period was 7.3 years; 77% survived for 10 years after study enrollment. Levels of alkaline phosphatase and bilirubin measured at study enrollment (baseline) and each year for 5 years were strongly associated with clinical outcomes (lower levels were associated with longer transplant-free survival). At 1 year after study enrollment, levels of alkaline phosphatase that were 2.0 times the upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other thresholds. Of patients with alkaline phosphatase levels 2.0 times the ULN (P < .0001). Absolute levels of alkaline phosphatase 1 year after study enrollment predicted patient outcomes better than percentage change in level. One year after study enrollment, a bilirubin level 1.0 times the ULN best predicted patient transplant-free survival (C statistic, 0.79). Of patients with bilirubin levels 1.0 times the ULN (P < .0001). Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times. We confirmed the predictive value of alkaline phosphatase and bilirubin levels in multiple subgroups, such as patients who had not received treatment with ursodeoxycholic acid, and at different time points after study enrollment. CONCLUSIONS: Levels of alkaline phosphatase and bilirubin can predict outcomes (liver transplantation or death) of patients with PBC and might be used as surrogate end points in therapy trials.
Published: 2014
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18. HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS

Author: Invernizzi, P, Selmi, C, Poli, F, Frison, S, Floreani, A, Alvaro, D, Almasio, P, Rosina, F, Marzioni, M, Fabris, L, Muratori, L, Qi, L, Seldin, Mf, Gershwin, Me, Podda, M, Andreoletti, M, Andriulli, A, Baldini, V, Battezzati, Pm, Benedetti, A, Bernuzzi, F, Bianchi, Fb, Bianchi, I, Bignotto, M, Bragazzi, Mc, Brunetto, M, Caimi, M, Caliari, L, Caporaso, N, Casella, G, Casiraghi, A, Colli, A, Colombo, M, Conte, D, Croce, L, Crosignani, A, Dottorini, L, Ferrari, C, Fraquelli, M, Frati, Ce, Galli, A, Lleo, A, Mancino, Mg, Mandelli, G, Marra, F, Montanari, R, Monti, V, Morini, L, Morisco, F, Niro, G, Palasciano, G, Calmieri, Vo, Pasini, S, Picciotto, A, Portincasa, P, Pozzoli, V, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, Pierluigi, Zerminai, P, Zuin, M., Invernizzi, P, Selmi, C, Poli, F, Frison, S, Floreani, A, Alvaro, D, Almasio, P, Rosina, F, Marzioni, M, Fabris, L, Muratori, L, Qi, L, Seldin, M, Gershwin, M, Podda, M, Andreoletti, M, Andriulli, A, Baldini, V, Battezzati, P, Benedetti, A, Bernuzzi, F, Bianchi, F, Bianchi, I, Bignotto, M, Bragazzi, M, Brunetto, M, Caimi, M, Caliari, L, Caporaso, N, Casella, G, Casiraghi, A, Colli, A, Colombo, M, Conte, D, Croce, L, Crosignani, A, Dottorini, L, Ferrari, C, Fraquelli, M, Frati, C, Galli, A, Lleo, A, Mancino, M, Mandelli, G, Marra, F, Montanari, R, Monti, V, Morini, L, Morisco, F, Niro, G, Palasciano, G, Calmieri, V, Pasini, S, Picciotto, A, Portincasa, P, Pozzoli, V, Spinzi, G, Strazzabosco, M, Tiribelli, C, Toniutto, P, Zerminai, P, Zuin, M, Invernizzi P, Selmi C, Poli F, Frison S, Floreani A, Alvaro D, Almasio P, Rosina F, Marzioni M, Fabris L, Muratori L, Qi L, Seldin MF, Gershwin ME, Podda M, Andreoletti M, Andriulli A, Baldini V, Battezzati PM, Benedetti A, Bernuzzi F, Bianchi FB, Bianchi I, Bignotto M, Bragazzi MC, Brunetto M, Caimi M, Caliari L, Caporaso N, Casella G, Casiraghi A, Colli A, Colombo M, Conte D, Croce L, Crosignani A, Dottorini L, Ferrari C, Fraquelli M, Frati CE, Galli A, Lleo A, Mancino MG, Mandelli G, Marra F, Montanari R, Monti V, Morini L, Morisco F, Niro G, Palasciano G, Calmieri VO, Pasini S, Picciotto A, Portincasa P, Pozzoli V, Spinzi G, Strazzabosco M, Tiribelli C, Toniutto P, Zerminai P, Zuin M., Invernizzi P, Selmi C, Poli F, Frison S, Floreani A, Alvaro D, Almasio P, Rosina F, Marzioni M, Fabris L, Muratori L, Qi L, Seldin MF, Gershwin ME, Podda M, Italian PBC Genetic Study Group, Seldin, Mf, Gershwin, Me, and Croce', Saveria
Subjects: Proband, Liver Cirrhosis, Male, Cohort Studies, Primary biliary cirrhosis, Gene Frequency, Models, Genotype, 80 and over, Medicine, skin and connective tissue diseases, Aged, 80 and over, Settore MED/12 - Gastroenterologia, Liver Cirrhosis, Biliary, Medicine (all), Biliary, Middle Aged, Italy, HLA-DRB1 Chain, Female, Case-Control Studie, Human, musculoskeletal diseases, Adult, Human leukocyte antigen, Article, Genetic, Genetic model, Humans, Genetic Predisposition to Disease, Polymorphism, Allele frequency, Aged, Polymorphism, Genetic, Hepatology, Models, Genetic, business.industry, Case-control study, Odds ratio, HLA-DR Antigens, medicine.disease, HLA-DR Antigen, Case-Control Studies, Immunology, primary bilairy cirrhosis, genetics, Cohort Studie, business, HLA-DRB1 Chains
Abstract: Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) were significantly associated with PBC, whereas alleles DRB1*11 (OR 0.4; 95% CI 0.3-0.4) and DRB1*13 (OR 0.7; 95% CI 0.6-0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients, whereas an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between speci fic DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease. Copyright © 2008 by the American Association for the Study of Liver Diseases.
Published: 2008

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18 results on '"Battezzati, P."'

1. A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon

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

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

4. Anti-phospholipid antibody prevalence and association with subclinical atherosclerosis and atherothrombosis in the general population

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

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

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

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

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

10. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score

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

12. Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome

13. Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis

14. Evolving Trends in Female to Male Incidence and Male Mortality of Primary Biliary Cholangitis

15. Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study

16. Development and Validation of a Scoring System to Predict Outcomes of Patients with Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy

17. Levels of Alkaline Phosphatase and Bilirubin Are Surrogate End Points of Outcomes of Patients With Primary Biliary Cirrhosis: An International Follow-up Study

18. HUMAN LEUKOCYTE ANTIGEN POLYMORPHISMS IN ITALIAN PRIMARY BILIARY CIRRHOSIS: A MULTICENTER STUDY OF 664 PATIENTS AND 1992 HEALTHY CONTROLS

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18 results on '"Battezzati, P."'

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