81 results on '"Malinverno F"'
Search Results
2. Survey on hepatic sarcoidosis in Italy
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Corte, C. Della, primary, Reati, R., additional, Malinverno, F., additional, Arena, I., additional, Campigotto, M., additional, Cardinale, V., additional, Cespiati, A., additional, Degasperi, E., additional, Del Poggio, P., additional, Durante, E., additional, Federico, A., additional, Galati, G., additional, Germani, G., additional, Giannini, G., additional, Marin, R., additional, Martini, A., additional, Mazzarelli, C., additional, Mirici, F., additional, Missale, G., additional, Morana, E., additional, Morelli, M., additional, Pasulo, L., additional, Piras, M., additional, Perricone, G., additional, Pugliese, N., additional, Rapetti, R., additional, Rendina, M., additional, Sciarrone, S., additional, Simone, L., additional, Surace, L., additional, Strona, S., additional, Svegliati B, G., additional, Viganò, M., additional, Manes, G., additional, and Carbone, M., additional
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- 2023
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3. Characteristics and medium-term outcomes of a retrospective cohort of patients with non-malignant, non-cirrhotic splanchnic vein thrombosis
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Gallo, C., primary, Manna, M., additional, Cristoferi, L., additional, Malinverno, F., additional, Ratti, L., additional, Gerussi, A., additional, Carbone, M., additional, Invernizzi, P., additional, and Ciaccio, A., additional
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- 2023
- Full Text
- View/download PDF
4. Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid
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De Vincentis, A, D'Amato, D, Cristoferi, L, Gerussi, A, Malinverno, F, Lleo, A, Colapietro, F, Marra, F, Galli, A, Fiorini, C, Coco, B, Brunetto, M, Niro, Ga, Cotugno, R, Saitta, C, Cozzolongo, R, Losito, F, Giannini, Eg, Labanca, S, Marzioni, M, Marconi, G, Morgando, A, Pellicano, R, Vanni, E, Cazzagon, N, Floreani, A, Chessa, L, Morelli, O, Muratori, L, Pellicelli, A, Pompili, M, Ponziani, F, Tortora, A, Rosina, F, Russello, M, Cannavo, M, Simone, L, Storato, S, Vigano, M, Abenavoli, L, D'Anto, M, De Gasperi, E, Distefano, M, Scifo, G, Zolfino, T, Calvaruso, V, Cuccorese, G, Palitti, Vp, Sacco, R, Bertino, G, Frazzetto, E, Alvaro, D, Mulinacci, G, Palermo, A, Scaravaglio, M, Terracciani, F, Galati, G, Ronca, V, Zuin, M, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Vespasiani-Gentilucci, U, Carbone, M, Feletti, V, Mussetto, A, Venere, R, Bernaccioni, G, Graciella Pigozzi, M, Fagiuoli, S, Terreni, N, Pozzoni, P, Baiocchi, L, Grassi, G, Vinci, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, De Vincentis, A, D'Amato, D, Cristoferi, L, Gerussi, A, Malinverno, F, Lleo, A, Colapietro, F, Marra, F, Galli, A, Fiorini, C, Coco, B, Brunetto, M, Niro, G, Cotugno, R, Saitta, C, Cozzolongo, R, Losito, F, Giannini, E, Labanca, S, Marzioni, M, Marconi, G, Morgando, A, Pellicano, R, Vanni, E, Cazzagon, N, Floreani, A, Chessa, L, Morelli, O, Muratori, L, Pellicelli, A, Pompili, M, Ponziani, F, Tortora, A, Rosina, F, Russello, M, Cannavo, M, Simone, L, Storato, S, Vigano, M, Abenavoli, L, D'Anto, M, De Gasperi, E, Distefano, M, Scifo, G, Zolfino, T, Calvaruso, V, Cuccorese, G, Palitti, V, Sacco, R, Bertino, G, Frazzetto, E, Alvaro, D, Mulinacci, G, Palermo, A, Scaravaglio, M, Terracciani, F, Galati, G, Ronca, V, Zuin, M, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Vespasiani-Gentilucci, U, Carbone, M, Feletti, V, Mussetto, A, Venere, R, Bernaccioni, G, Graciella Pigozzi, M, Fagiuoli, S, Terreni, N, Pozzoni, P, Baiocchi, L, Grassi, G, Vinci, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, Niro, GA, Giannini, EG, and Palitti, VP
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Liver Cirrhosis ,Male ,liver decompensation ,safety ,Hepatology ,Liver Cirrhosis, Biliary ,decision curve analysis ,efficacy ,total bilirubin ,Albumins ,Ascites ,Bilirubin ,Chenodeoxycholic Acid ,Humans ,Biliary ,decision curve analysi ,Settore MED/12 - Abstract
Background & Aims Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. Methods Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin >= 1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. Conclusions An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level >= 1.4 mg/dl should discourage from its use.
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- 2022
5. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))
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Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byun, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byun J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M.C., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V.J., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D.J., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J.W., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., and Millson C.
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PBC - Abstract
It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused.
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- 2022
6. Long‐term outcomes of direct acting antivirals in post‐transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis
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Vukotic, R., Conti, F., Fagiuoli, S., Morelli, M. C., Pasulo, L., Colpani, M., Foschi, F. G., Berardi, S., Pianta, P., Mangano, M., Donato, M. F., Malinverno, F., Monico, S., Tamè, M., Mazzella, G., Belli, L. S., Viganò, R., Carrai, P., Burra, P., Russo, F. P., Lenci, I., Toniutto, P., Merli, M., Loiacono, L., Iemmolo, R., Degli Antoni, A. M., Romano, A., Picciotto, A., Rendina, M., and Andreone, P.
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- 2017
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7. Predictors of Serious Adverse Event and Non-response in Cirrhotic Patients With Primary Biliary Cholangitis under Obeticholic Acid
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De Vincentis, A., primary, D'Amato, D., additional, Cristoferi, L., additional, Gerussi, A., additional, Malinverno, F., additional, Lleo, A., additional, Colapietro, F., additional, Marra, F., additional, Galli, A., additional, Fiorini, C., additional, Coco, B., additional, Brunetto, M., additional, Niro, G.A., additional, Cotugno, R., additional, Saitta, C., additional, Cozzolongo, R., additional, Losito, F., additional, Giannini, E.G., additional, Labanca, S., additional, Marzioni, M., additional, Marconi, G., additional, Morgando, A., additional, Pellicano, R., additional, Vanni, E., additional, Cazzagon, N., additional, Floreani, A., additional, Chessa, L., additional, Morelli, O., additional, Muratori, L., additional, Pellicelli, A., additional, Pompili, M., additional, Ponziani, F., additional, Rosina, F., additional, Russello, M., additional, Cannavò, M., additional, Simone, L., additional, Storato, S., additional, Viganò, M., additional, Abenavoli, L., additional, D'Antò, M., additional, De Gasperi, E., additional, Distefano, M., additional, Scifo, G., additional, Zolfino, T., additional, Calvaruso, V., additional, Cuccorese, G., additional, Pace Palitti, V., additional, Sacco, R., additional, Bertino, G., additional, Frazzetto, E., additional, Alvaro, D., additional, Mulinacci, G., additional, Palermo, A., additional, Galati, G., additional, Ronca, V., additional, Zuin, M., additional, Claar, E., additional, Izzi, A., additional, Picardi, A., additional, Invernizzi, P., additional, Vespasiani-Gentilucci, U., additional, and Carbone, M., additional
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- 2022
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8. Additive beneficial effects of Fibrates combined with Obeticholic acid in the treatment of patients with Primary Biliary Cholangitis and inadequate response to second-line therapy: data from the Italian PBC Study Group
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D’Amato, D., primary, O’Donnell, S.E., additional, Cazzagon, N., additional, Marconi, G., additional, Gerussi, A., additional, Cristoferi, L., additional, Malinverno, F., additional, Mancuso, C., additional, Milani, C., additional, Marzioni, M., additional, Floreani, A., additional, Invernizzi, P., additional, and Carbone, M., additional
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- 2020
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9. Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre- to post-liver transplant: A real-life strategy
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Donato, M. F., Morelli, C., Romagnoli, R., Invernizzi, F., Mazzarelli, C., Iemmolo, R. M., Montalbano, M., Lenci, I., Bhoori, S., Pieri, G., Berardi, S., Caraceni, P., Martini, S., Angeli, P., Belli, L. S., Bernabucci, V., Malinverno, F., Monico, S., Ottobrelli, A., Romano, A., Strona, S., Tame, M. R., Visco-Comandini, U., Cavenago, M., De Carlis, L., Di Benedetto, F., Dondossola, D., Ettorre, G. M., Mazzaferro, V., Montin, U., Pinna, A. D., Rossi, G., Salizzoni, M., Tisone, G., Donato, Maria Francesca, Morelli, Cristina, Romagnoli, Renato, Invernizzi, Federica, Mazzarelli, Chiara, Iemmolo, Rosa Maria, Montalbano, Marzia, Lenci, Ilaria, Bhoori, Sherrie, Pieri, Giulia, Berardi, Sonia, Caraceni, Paolo, Martini, Silvia, Donato, M, Morelli, C, Romagnoli, R, Invernizzi, F, Mazzarelli, C, Iemmolo, R, Montalbano, M, Lenci, I, Bhoori, S, Pieri, G, Berardi, S, Caraceni, P, Martini, S, Angeli, P, Belli, L, Bernabucci, V, Malinverno, F, Monico, S, Ottobrelli, A, Romano, A, Strona, S, Tamè, M, Visco-Comandini, U, Cavenago, M, De Carlis, L, Di Benedetto, F, Dondossola, D, Ettorre, G, Mazzaferro, V, Montin, U, Pinna, A, Rossi, G, Salizzoni, M, and Tisone, G
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Liver Cirrhosis ,Male ,Sofosbuvir ,Sustained Virologic Response ,Hepatocellular carcinoma ,medicine.medical_treatment ,Hepacivirus ,Liver transplantation ,medicine.disease_cause ,hepatitis C ,hepatocellular carcinoma ,liver transplant ,sofosbuvir therapy ,virological response ,Adult ,Aged ,Antiviral Agents ,Carcinoma, Hepatocellular ,Drug Therapy, Combination ,Female ,Hepatitis C ,Humans ,Italy ,Liver Neoplasms ,Middle Aged ,Postoperative Period ,Preoperative Period ,Recurrence ,Retrospective Studies ,Ribavirin ,Liver Transplantation ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Sofosbuvir therapy ,Retrospective Studie ,Liver transplant ,Virological response ,Liver Neoplasm ,030220 oncology & carcinogenesis ,Combination ,030211 gastroenterology & hepatology ,Viral hepatitis ,Human ,medicine.drug ,medicine.medical_specialty ,Liver Cirrhosi ,Hepatitis C virus ,03 medical and health sciences ,Hepatology ,Drug Therapy ,Internal medicine ,medicine ,Antiviral Agent ,Hepaciviru ,business.industry ,Carcinoma ,Hepatocellular ,medicine.disease ,Settore MED/18 ,Surgery ,Regimen ,chemistry ,business - Abstract
Background and aims Hepatitis C virus (HCV) reinfection following liver transplant (LT) is associated with reduced graft and patients survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 week HCV-RNA undetectability at the time of transplant. Material and Methods From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One-hundred were transplanted and 31 patients (31%) treated by SOF/R bridging therapy were studied Results LT indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/ml). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in 4 recipients. On September 2016, 30 recipients (97%) are alive with a median follow-up of 18 months (range 13-25). Conclusions In patients with suboptimal virological response at LT a bridging SOF/R regimen helps avoiding post-transplant graft reinfection. This article is protected by copyright. All rights reserved.
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- 2017
10. Shedding light on the X chromosome contribution to the genetic architecture of primary biliary cholangitis
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Gerussi, A., primary, Asselta, R., additional, Paraboschi, E., additional, Carbone, M., additional, Ronca, V., additional, Cristoferi, L., additional, Malinverno, F., additional, Duga, S., additional, and Invernizzi, P., additional
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- 2019
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11. A chromosome X-wide association study in primary biliary cholangitis allowed the identification of 5 novel susceptibility loci
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Asselta, R., primary, Paraboschi, E., additional, Carbone, M., additional, Gerussi, A., additional, Ronca, V., additional, Cristoferi, L., additional, Malinverno, F., additional, Duga, S., additional, and Invernizzi, P., additional
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- 2018
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12. Incidence, prevalence and mortality of Primary Sclerosing Cholangitis (PSC) in Italy: A population-based study
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Carbone, M., primary, Rocchetti, A., additional, Kodra, Y., additional, Manno, V., additional, Minelli, G., additional, Malinverno, F., additional, Floreani, A., additional, Invernizzi, P., additional, Conti, S., additional, and Taruscio, D., additional
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- 2018
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13. Pre-treatment risk stratification in primary biliary cholangitis: A predictive model to guide first-line combination therapy
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Carbone, M., primary, Nardi, A., additional, Carpino, G., additional, Cardinale, V., additional, Ainsworth, H., additional, Heneghan, M., additional, Thorburn, D., additional, Bathgate, A., additional, Jones, R., additional, Neuberger, J.M., additional, Battezzati, P.M., additional, Zuin, M., additional, Taylor-Robinson, S., additional, Donato, M., additional, Kirby, J., additional, Mitchell-Thain, R., additional, Floreani, A., additional, Sampaziotis, F., additional, Muratori, L., additional, Alvaro, D., additional, Marzioni, M., additional, Miele, L., additional, Marra, F., additional, Giannini, E., additional, Gaudio, E., additional, Ronca, V., additional, Bonato, G., additional, Cristoferi, L., additional, Malinverno, F., additional, Gerussi, A., additional, Cordell, H.J., additional, Hirschfield, G.M., additional, Stocken, D., additional, Alexander, G.J., additional, Sandford, R.N., additional, Jones, D.E., additional, Invernizzi, P., additional, and Mells, G.F., additional
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- 2018
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14. A worldwide cross-ethnic study of quality of life in patients with PBC: Attitude or latitude?
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Carbone, M., primary, Montali, L., additional, Gragnano, A., additional, Miglioretti, M., additional, Frigerio, A., additional, Yagi, M., additional, Malinverno, F., additional, Bernuzzi, F., additional, Jopson, L., additional, Reig, A., additional, Pilar, S., additional, Pares, A., additional, Tanaka, A., additional, Mells, G.F., additional, Jones, D.E., additional, and Invernizzi, P., additional
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- 2018
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15. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants
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Juran BD, Hirschfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, Kosoy R, Ransom M, Sun Y, Bianchi I, Schlicht EM, Lleo A, Coltescu C, Bernuzzi F, Podda M, Lammert C, Shigeta R, Chan LL, Balschun T, Marconi M, Cusi D, Heathcote EJ, Mason AL, Myers RP, Milkiewicz P, Odin JA, Luketic VA, Bacon BR, Bodenheimer HC Jr, Liakina V, Vincent C, Levy C, Franke A, Gregersen PK, Bossa F, Gershwin ME, deAndrade M, Amos CI, Italian PBC Genetics Study Group, Lazaridis KN, Seldin MF, Siminovitch KA, Almasio PL, Alvaro D, Andriulli A, Barlassina C, Battezzati PM, Benedetti A, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Civardi F, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Crocè LS, Crosignani A, Donato F, Fabris L, Ferrari C, Floreani A, Fontana R, Galli A, Grattagliano I, Lazzari R, Macaluso F, Malinverno F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Niro GA, Picciotto A, Portincasa P, Prati D, Rosina F, Rossi S, Selmi C, Spinzi G, Strazzabosco M, Tarallo S, Tiribelli C, Toniutto P, Vinci M, Zuin M., ANDREONE, PIETRO, MURATORI, LUIGI, MURATORI, PAOLO, Juran BD, Hirschfield GM, Invernizzi P, Atkinson EJ, Li Y, Xie G, Kosoy R, Ransom M, Sun Y, Bianchi I, Schlicht EM, Lleo A, Coltescu C, Bernuzzi F, Podda M, Lammert C, Shigeta R, Chan LL, Balschun T, Marconi M, Cusi D, Heathcote EJ, Mason AL, Myers RP, Milkiewicz P, Odin JA, Luketic VA, Bacon BR, Bodenheimer HC Jr, Liakina V, Vincent C, Levy C, Franke A, Gregersen PK, Bossa F, Gershwin ME, deAndrade M, Amos CI, Italian PBC Genetics Study Group, Lazaridis KN, Seldin MF, Siminovitch KA, Almasio PL, Alvaro D, Andreone P, Andriulli A, Barlassina C, Battezzati PM, Benedetti A, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Civardi F, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Crocè LS, Crosignani A, Donato F, Fabris L, Ferrari C, Floreani A, Fontana R, Galli A, Grattagliano I, Lazzari R, Macaluso F, Malinverno F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Muratori L, Muratori P, Niro GA, Picciotto A, Portincasa P, Prati D, Rosina F, Rossi S, Selmi C, Spinzi G, Strazzabosco M, Tarallo S, Tiribelli C, Toniutto P, Vinci M, Zuin M., Juran, Bd, Hirschfield, Gm, Invernizzi, P, Atkinson, Ej, Li, Y, Xie, G, Kosoy, R, Ransom, M, Sun, Y, Bianchi, I, Schlicht, Em, Lleo, A, Coltescu, C, Bernuzzi, F, Podda, M, Lammert, C, Shigeta, R, Chan, Ll, Balschun, T, Marconi, M, Cusi, D, Heathcote, Ej, Mason, Al, Myers, Rp, Milkiewicz, P, Odin, Ja, Luketic, Va, Bacon, Br, Bodenheimer HC, Jr, Liakina, V, Vincent, C, Levy, C, Franke, A, Gregersen, Pk, Bossa, F, Gershwin, Me, Deandrade, M, Amos, Ci, Lazaridis, Kn, Seldin, Mf, Siminovitch, Ka, Morisco, Filomena, Italian PBC Genetics Study, Group, Juran, B, Hirschfield, G, Atkinson, E, Schlicht, E, Chan, L, Heathcote, E, Mason, A, Myers, R, Odin, J, Luketic, V, Bacon, B, Bodenheimer, H, Gregersen, P, Gershwin, M, Amos, C, Italian PBC Genetics Study, G, Lazaridis, K, Seldin, M, Siminovitch, K, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Caliari, L, Casella, G, Civardi, F, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, L, Crosignani, A, Donato, F, Fabris, L, Ferrari, C, Floreani, A, Fontana, R, Galli, A, Grattagliano, I, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mascia, E, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, Picciotto, A, Portincasa, P, Prati, D, Rosina, F, Rossi, S, Selmi, C, Spinzi, G, Strazzabosco, M, Tarallo, S, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Almasio, Pl, Battezzati, Pm, Croce', Saveria, Niro, Ga, Tiribelli, Claudio, and Zuin, M.
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MULTILOCUS GENOTYPE DATA ,PRIMARY BILIARY CIRRHOSIS ,PBC ,0302 clinical medicine ,Gene Frequency ,MED/12 - GASTROENTEROLOGIA ,HLA Antigens ,REGULATORY T-CELLS ,RHEUMATOID-ARTHRITIS ,VITAMIN-D ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Genetics ,CLASSICAL HLA ALLELES ,0303 health sciences ,Liver Cirrhosis, Biliary ,PBC, HLA alleles ,Association Studies Articles ,CELIAC-DISEASE ,General Medicine ,GENOME-WIDE ASSOCIATION ,SUSCEPTIBILITY LOCI ,GENETIC RISK ,3. Good health ,Chromosomes, Human, Pair 1 ,SINGLE NUCLEOTIDE POLYMORPHISMS ,030211 gastroenterology & hepatology ,Chromosomes, Human, Pair 7 ,GENETIC ANALYSES ,Genotype ,Single-nucleotide polymorphism ,Locus (genetics) ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Humans ,SNP ,Genetic Predisposition to Disease ,Allele ,Molecular Biology ,Allele frequency ,Alleles ,030304 developmental biology ,Chromosomes, Human, Pair 13 ,Haplotype ,Epistasis, Genetic ,Genetic Loci ,Case-Control Studies ,Imputation (genetics) - Abstract
To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.
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- 2012
16. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
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Cordell, HJ, Han, Y, Mells, GF, Li, Y, Hirschfield, GM, Greene, CS, Xie, G, Juran, BD, Zhu, D, Qian, DC, Floyd, JAB, Morley, KI, Prati, D, Lleo, A, Cusi, D, Gershwin, ME, Anderson, CA, Lazaridis, KN, Invernizzi, P, Seldin, MF, Sandford, RN, Amos, CI, Siminovitch, KA, Schlicht, EM, Lammert, C, Atkinson, EJ, Chan, LL, De Andrade, M, Balschun, T, Mason, AL, Myers, RP, Zhang, J, Milkiewicz, P, Qu, J, Odin, JA, Luketic, VA, Bacon, BR, Bodenheimer, HC, Liakina, V, Vincent, C, Levy, C, Gregersen, PK, Almasio, PL, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, PM, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, MC, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, LS, Crosignani, A, Donato, MF, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Mousa Hani, S, Muratori, L, Muratori, P, Niro, GA, Palmieri, VO, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, and Spreafico, M
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MD Multidisciplinary - Abstract
© 2015 Macmillan Publishers Limited. All rights reserved.Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined
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- 2015
17. PC.01.1 MANAGEMENT OF BILIARY ANASTOMOTIC STRICTURE AFTER LIVER TRANSPLANTATION (BASALT STUDY): RESULTS OF A NATIONAL SURVEY IN ITALY
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Cantù, P., primary, Parzanese, I., additional, Balassone, V., additional, Di Sario, A., additional, Soggiu, F., additional, Lombardi, G., additional, Barbaro, F., additional, Pisani, A., additional, Baldan, A., additional, Cariani, G., additional, Boarino, V., additional, Fasoli, A., additional, Bertani, H., additional, Forti, E., additional, Bulajic, M., additional, Ghinolfi, D., additional, Nadal, E., additional, Cerofolini, A., additional, Barresi, L., additional, Stroppa, I., additional, Mazzaferro, V., additional, Cipolletta, L., additional, Tringali, A., additional, Costamagna, G., additional, Ravelli, P., additional, Bazzoli, F., additional, Merighi, A., additional, Parodi, M.C., additional, Conigliaro, R., additional, Mutignani, M., additional, Zilli, M., additional, Filipponi, F., additional, Fantin, A., additional, Rodella, L., additional, Traina, M., additional, Rotondano, G., additional, Rosa, R., additional, Malinverno, F., additional, Donato, F., additional, Colombo, M., additional, Conte, D., additional, Rossi, G., additional, and Penagini, R., additional
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- 2016
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18. Lack of Improvement of Liver Stiffness during Sofosbuvir-Treatment in Decompensated Cirrhotic Patients Listed for Liver Transplant Seems to be Associated with more Severe Histological Damage in the Native Liver
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Invernizzi, F., primary, Malinverno, F., additional, Maggioni, M., additional, Sciarra, A., additional, Aghemo, A., additional, Dondossola, D., additional, Rossi, G., additional, Colombo, M., additional, and Donato, M.F., additional
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- 2016
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19. P0903 : Slow HCV kinetics following sofosbuvir + ribavirin administration in real-life setting of liver transplant recipients with severe recurrent hepatitis C
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Cento, V., primary, Donato, M.F., additional, Lenci, I., additional, Rendina, M., additional, Milana, M., additional, Di Maio, V.C., additional, Monico, S., additional, Aragri, M., additional, Alfieri, R., additional, Abedrabbo, A., additional, Sforza, D., additional, Manuelli, M., additional, Mameli, L., additional, Sorbo, M.C., additional, Canu, R., additional, Ponti, M.L., additional, Chialà, C., additional, Malinverno, F., additional, Marenco, S., additional, Milanesi, L., additional, Picciotto, A., additional, Rossi, G., additional, Di Leo, A., additional, Tisone, G., additional, Zamboni, F., additional, Ganga, R., additional, Colombo, M., additional, Perno, C.F., additional, Angelico, M., additional, and Ceccherini-Silberstein, F., additional
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- 2015
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20. LP51 : Treatment of severe HCV recurrence after liver transplantation with sofosbuvir based regimen: Results of the aisf-sofolt Italian compassionate use program
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Andreone, P., primary, Conti, F., additional, Vukotic, R., additional, Fagiuoli, S., additional, Morelli, M.C., additional, Pasulo, L., additional, Colpani, M., additional, Berardi, S., additional, Foschi, F.G., additional, Pianta, P., additional, Donato, M.F., additional, Malinverno, F., additional, Mazzella, G., additional, Tamè, M., additional, Belli, L.S., additional, Viganò, R., additional, Carrai, P., additional, Burra, P., additional, Russo, F.P., additional, Lenci, I., additional, Toniutto, P., additional, Merli, M., additional, Loiacono, L., additional, Iemmolo, R.M., additional, Degli Antoni, A., additional, Romano, A., additional, Picciotto, A., additional, and Rendina, M., additional
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- 2015
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21. Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir+ribavirin: possible clinical implications in the liver transplant list management
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Lenci, I., primary, Cento, V., additional, Rendina, M., additional, Donato, M.F., additional, Milana, M., additional, Sforza, D., additional, Manuelli, M., additional, Aragri, M., additional, Di Maio, V.C., additional, Abedrabbo, A., additional, Castellaneta, A., additional, Malinverno, F., additional, Monico, S., additional, Ponti, M.L., additional, Canu, R., additional, Ganga, R., additional, Alfieri, R., additional, Milanesi, L., additional, Di Leo, A., additional, Tisone, G., additional, Perno, C.F., additional, Ceccherini-Silberstein, F., additional, Colombo, M., additional, and Angelico, M., additional
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- 2015
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22. FRI-473 - Lack of Improvement of Liver Stiffness during Sofosbuvir-Treatment in Decompensated Cirrhotic Patients Listed for Liver Transplant Seems to be Associated with more Severe Histological Damage in the Native Liver
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Invernizzi, F., Malinverno, F., Maggioni, M., Sciarra, A., Aghemo, A., Dondossola, D., Rossi, G., Colombo, M., and Donato, M.F.
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- 2016
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23. Slow achievement of HCV-RNA undetectability in cirrhotic patients treated with sofosbuvir + ribavirin: possible clinical implications in the liver transplant list management
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Lenci, I., Cento, V., Rendina, M., Donato, M.F., Milana, M., Sforza, D., Manuelli, M., Aragri, M., Di Maio, V.C., Abedrabbo, A., Castellaneta, A., Malinverno, F., Monico, S., Ponti, M.L., Canu, R., Ganga, R., Alfieri, R., Milanesi, L., Di Leo, A., Tisone, G., Perno, C.F., Ceccherini-Silberstein, F., Colombo, M., and Angelico, M.
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- 2015
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24. Preventive administration of ursodeoxycholic acid after liver transplantation for primary biliary cholangitis prevents disease recurrence and prolongs graft survival
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Corpechot, C., Chazouilleres, O., Montano-Loza, A. J., Mason, A. L., Ebadi, M., Eurich, D., Chopra, S., Jacob, D., Schramm, C., Sterneck, M., Tony Bruns, Reuken, P., Rauchfuss, F., Hansen, B. E., Roccarina, D., Thorburn, D., Trivedi, P., Hirschfield, G., Mcdowell, P., Boillot, O., Bosch, A., Giostria, E., Conti, F., Poupon, R., Pares, A., Reig, A., Floreani, A., Russo, F. P., Goet, J., Harms, M., Buuren, H., Den Ende, N., Nevens, F., Verhelst, X., Donato, M. F., Malinverno, F., Belnou, P., Carrat, F., and Dumortier, J.
25. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort
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Maria Giovanna Quaranta, Luigina Ferrigno, Xhimi Tata, Franca D'Angelo, Marco Massari, Carmine Coppola, Elisa Biliotti, Alessia Giorgini, Diletta Laccabue, Alessia Ciancio, Pier Luigi Blanc, Marzia Margotti, Donatella Ieluzzi, Maurizia Rossana Brunetto, Francesco Barbaro, Francesco Paolo Russo, Ilaria Beretta, Giulia Morsica, Gabriella Verucchi, Annalisa Saracino, Massimo Galli, Loeta A. Kondili, Cesare Mazzaro, Manuela Bertola, Ornella Schioppa, Antonio Benedetti, Laura Schiadà, Monica Cucco, Andrea Giacometti, Laura Brescini, Sefora Castelletti, Alessandro Fiorentini, Gioacchino Angarano, Michele Milella, Alfredo Di Leo, Maria Rendina, Fulvio Salvatore D'abramo, Chiara Lillo, Andrea Iannone, Mariano Piazzolla, Lorenzo Badia, Fabio Piscaglia, Francesca Benevento, Ilaria Serio, Francesco Castelli, Serena Zaltron, Angiola Spinetti, Silvia Odolini, Raffaele Bruno, Mario Mondelli, Luchino Chessa, Martina Loi, Carlo Torti, Chiara Costa, Maria Mazzitelli, Vincenzo Pisani, Vincenzo Scaglione, Enrico Maria Trecarichi, Anna Linda Zignego, Monica Monti, Francesco Madia, Letizia Attala, Piera Pierotti, Elena Salomoni, Elisa Mariabelli, Teresa Antonia Santantonio, Serena Rita Bruno, Ester Marina Cela, Matteo Bassetti, Giovanni Mazzarello, Anna Ida Alessandrini, Antonio Di Biagio, Laura Ambra Nicolini, Giovanni Raimondo, Roberto Filomia, Alessio Aghemo, Rossella Meli, Adriano Lazzarin, Stefania Salpietro, Anna Ludovica Fracanzani, Erika Fatta, Rosa Lombardi, Pietro Lampertico, Marta Borghi, Roberta D'ambrosio, Elisabetta Degasperi, Massimo Puoti, Chiara Baiguera, Federico D'amico, Maria Vinci, Maria Grazia Rumi, Massimo Zuin, Paola Zermiani, Pietro Andreone, Paolo Caraceni, Valeria Guarneri, Erica Villa, Veronica Bernabucci, Laura Bristot, Maria Luisa Paradiso, Guglielmo Migliorino, Alessandra Gambaro, Giuseppe Lapadula, Anna Spolti, Alessandro Soria, Pietro Invernizzi, Antonio Ciaccio, Martina LucÀ, Federica Malinverno, Laura Ratti, Daniela Caterina Amoruso, Federica Pisano, Ferdinando Scarano, Laura Staiano, Filomena Morisco, Valentina Cossiga, Ivan Gentile, Antonio Riccardo Buonomo, Maria Foggia, Emanuela Zappulo, Alessandro Federico, Marcello Dallio, Nicola Coppola, Caterina Sagnelli, Salvatore Martini, Caterina Monari, Gerardo Nardone, Costantino Sgamato, Liliana Chemello, Luisa Cavalletto, Daniela Sterrantino, Alberto Zanetto, Paola Zanaga, Giuseppina Brancaccio, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Luciano Crapanzano, Salvatore Madonia, Marco Cannizzaro, Erica Maria Bruno, Anna Licata, Simona Amodeo, Adele Rosaria Capitano, Carlo Ferrari, Elisa Negri, Alessandra Orlandini, Marco Pesci, Roberto Gulminetti, Layla Pagnucco, Giustino Parruti, Paola Di Stefano, Barbara Coco, Romina Corsini, Elisa Garlassi, Massimo Andreoni, Elisabetta Teti, Carlotta Cerva, Lorenzo Baiocchi, Giuseppe Grassi, Antonio Gasbarrini, Maurizio Pompili, Martina De Siena, Gloria Taliani, Martina Spaziante, Marcello Persico, Mario Masarone, Andrea Aglitti, Gemma Calvanese, Marco Anselmo, Pasqualina De Leo, Monica Marturano, Giorgio Maria Saracco, Quaranta M.G., Ferrigno L., Tata X., D'Angelo F., Massari M., Coppola C., Biliotti E., Giorgini A., Laccabue D., Ciancio A., Blanc P.L., Margotti M., Ieluzzi D., Brunetto M.R., Barbaro F., Russo F.P., Beretta I., Morsica G., Verucchi G., Saracino A., Galli M., Kondili L.A., Mazzaro C., Bertola M., Benedetti A., Schiada L., Cucco M., Giacometti A., Brescini L., Castelletti S., Fiorentini A., Angarano G., Milella M., Leo A.D., Rendina M., Salvatore D'ABRAMO F., Lillo C., Iannone A., Piazzolla M., Badia L., Piscaglia F., Benevento F., Serio I., Castelli F., Zaltron S., Spinetti A., Odolini S., Bruno R., Mondelli M., Chessa L., Loi M., Torti C., Costa C., Mazzitelli M., Pisani V., Scaglione V., Trecarichi E.M., Zignego A.L., Monti M., Madia F., Attala L., Pierotti P., Salomoni E., Mariabelli E., Santantonio T.A., Bruno S.R., Cela E.M., Bassetti M., Mazzarello G., Alessandrini A.I., Biagio A.D., Nicolini L.A., Raimondo G., Filomia R., Aghemo A., Meli R., Lazzarin A., Salpietro S., Fracanzani A.L., Fatta E., Lombardi R., Lampertico P., Borghi M., D'ambrosio R., Degasperi E., Puoti M., Baiguera C., D'AMICO F., Vinci M., Rumi M.G., Zuin M., Zermiani P., Andreone P., Caraceni P., Guarneri V., Villa E., Bernabucci V., Bristot L., Paradiso M.L., Migliorino G., Gambaro A., Lapadula G., Spolti A., Soria A., Invernizzi P., Ciaccio A., LucA M., Malinverno F., Ratti L., Amoruso D.C., Pisano F., Scarano F., Staiano L., Morisco F., Cossiga V., Gentile I., Buonomo A.R., Foggia M., Zappulo E., Federico A., Dallio M., Coppola N., Sagnelli C., Martini S., Monari C., Nardone G., Sgamato C., Chemello L., Cavalletto L., Sterrantino D., Zanetto A., Zanaga P., Brancaccio G., Craxi A., Petta S., Calvaruso V., Crapanzano L., Madonia S., Cannizzaro M., Bruno E.M., Licata A., Amodeo S., Capitano A.R., Ferrari C., Negri E., Orlandini A., Pesci M., Gulminetti R., Pagnucco L., Parruti G., Stefano P.D., Coco B., Corsini R., Garlassi E., Andreoni M., Teti E., Cerva C., Baiocchi L., Grassi G., Gasbarrini A., Pompili M., Siena M.D., Taliani G., Spaziante M., Persico M., Masarone M., Aglitti A., Calvanese G., Anselmo M., Leo P.D., Marturano M., Saracco G.M., Quaranta, M, Ferrigno, L, Tata, X, D'Angelo, F, Massari, M, Coppola, C, Biliotti, E, Giorgini, A, Laccabue, D, Ciancio, A, Blanc, P, Margotti, M, Ieluzzi, D, Brunetto, M, Barbaro, F, Russo, F, Beretta, I, Morsica, G, Verucchi, G, Saracino, A, Galli, M, Kondili, L, Mazzaro, C, Bertola, M, Benedetti, A, Schiada, L, Cucco, M, Giacometti, A, Brescini, L, Castelletti, S, Fiorentini, A, Angarano, G, Milella, M, Leo, A, Rendina, M, Salvatore D'ABRAMO, F, Lillo, C, Iannone, A, Piazzolla, M, Badia, L, Piscaglia, F, Benevento, F, Serio, I, Castelli, F, Zaltron, S, Spinetti, A, Odolini, S, Bruno, R, Mondelli, M, Chessa, L, Loi, M, Torti, C, Costa, C, Mazzitelli, M, Pisani, V, Scaglione, V, Trecarichi, E, Zignego, A, Monti, M, Madia, F, Attala, L, Pierotti, P, Salomoni, E, Mariabelli, E, Santantonio, T, Bruno, S, Cela, E, Bassetti, M, Mazzarello, G, Alessandrini, A, Biagio, A, Nicolini, L, Raimondo, G, Filomia, R, Aghemo, A, Meli, R, Lazzarin, A, Salpietro, S, Fracanzani, A, Fatta, E, Lombardi, R, Lampertico, P, Borghi, M, D'Ambrosio, R, Degasperi, E, Puoti, M, Baiguera, C, D'Amico, F, Vinci, M, Rumi, M, Zuin, M, Zermiani, P, Andreone, P, Caraceni, P, Guarneri, V, Villa, E, Bernabucci, V, Bristot, L, Paradiso, M, Migliorino, G, Gambaro, A, Lapadula, G, Spolti, A, Soria, A, Invernizzi, P, Ciaccio, A, Luca, M, Malinverno, F, Ratti, L, Amoruso, D, Pisano, F, Scarano, F, Staiano, L, Morisco, F, Cossiga, V, Gentile, I, Buonomo, A, Foggia, M, Zappulo, E, Federico, A, Dallio, M, Coppola, N, Sagnelli, C, Martini, S, Monari, C, Nardone, G, Sgamato, C, Chemello, L, Cavalletto, L, Sterrantino, D, Zanetto, A, Zanaga, P, Brancaccio, G, Craxi, A, Petta, S, Calvaruso, V, Crapanzano, L, Madonia, S, Cannizzaro, M, Bruno, E, Licata, A, Amodeo, S, Capitano, A, Ferrari, C, Negri, E, Orlandini, A, Pesci, M, Gulminetti, R, Pagnucco, L, Parruti, G, Stefano, P, Coco, B, Corsini, R, Garlassi, E, Andreoni, M, Teti, E, Cerva, C, Baiocchi, L, Grassi, G, Gasbarrini, A, Pompili, M, Siena, M, Taliani, G, Spaziante, M, Persico, M, Masarone, M, Aglitti, A, Calvanese, G, Anselmo, M, Leo, P, Marturano, M, Saracco, G, Quaranta, M. G., Ferrigno, L., Tata, X., D'Angelo, F., Massari, M., Coppola, C., Biliotti, E., Giorgini, A., Laccabue, D., Ciancio, A., Blanc, P. L., Margotti, M., Ieluzzi, D., Brunetto, M. R., Barbaro, F., Russo, F. P., Beretta, I., Morsica, G., Verucchi, G., Saracino, A., Galli, M., Kondili, L. A., Mazzaro, C., Bertola, M., Benedetti, A., Schiada, L., Cucco, M., Giacometti, A., Brescini, L., Castelletti, S., Fiorentini, A., Angarano, G., Milella, M., Leo, A. D., Rendina, M., Salvatore D'ABRAMO, F., Lillo, C., Iannone, A., Piazzolla, M., Badia, L., Piscaglia, F., Benevento, F., Serio, I., Castelli, F., Zaltron, S., Spinetti, A., Odolini, S., Bruno, R., Mondelli, M., Chessa, L., Loi, M., Torti, C., Costa, C., Mazzitelli, M., Pisani, V., Scaglione, V., Trecarichi, E. M., Zignego, A. L., Monti, M., Madia, F., Attala, L., Pierotti, P., Salomoni, E., Mariabelli, E., Santantonio, T. A., Bruno, S. R., Cela, E. M., Bassetti, M., Mazzarello, G., Alessandrini, A. I., Biagio, A. D., Nicolini, L. A., Raimondo, G., Filomia, R., Aghemo, A., Meli, R., Lazzarin, A., Salpietro, S., Fracanzani, A. L., Fatta, E., Lombardi, R., Lampertico, P., Borghi, M., D'Ambrosio, R., Degasperi, E., Puoti, M., Baiguera, C., D'Amico, F., Vinci, M., Rumi, M. G., Zuin, M., Zermiani, P., Andreone, P., Caraceni, P., Guarneri, V., Villa, E., Bernabucci, V., Bristot, L., Paradiso, M. L., Migliorino, G., Gambaro, A., Lapadula, G., Spolti, A., Soria, A., Invernizzi, P., Ciaccio, A., Luca, M., Malinverno, F., Ratti, L., Amoruso, D. C., Pisano, F., Scarano, F., Staiano, L., Morisco, F., Cossiga, V., Gentile, I., Buonomo, A. R., Foggia, M., Zappulo, E., Federico, A., Dallio, M., Coppola, N., Sagnelli, C., Martini, S., Monari, C., Nardone, G., Sgamato, C., Chemello, L., Cavalletto, L., Sterrantino, D., Zanetto, A., Zanaga, P., Brancaccio, G., Craxi, A., Petta, S., Calvaruso, V., Crapanzano, L., Madonia, S., Cannizzaro, M., Bruno, E. M., Licata, A., Amodeo, S., Capitano, A. R., Ferrari, C., Negri, E., Orlandini, A., Pesci, M., Gulminetti, R., Pagnucco, L., Parruti, G., Stefano, P. D., Coco, B., Corsini, R., Garlassi, E., Andreoni, M., Teti, E., Cerva, C., Baiocchi, L., Grassi, G., Gasbarrini, A., Pompili, M., Siena, M. D., Taliani, G., Spaziante, M., Persico, M., Masarone, M., Aglitti, A., Calvanese, G., Anselmo, M., Leo, P. D., Marturano, M., and Saracco, G. M.
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Male ,HCV genotypes ,Ethnic group ,Linked-to-care patient ,Comorbidity ,Hepacivirus ,Logistic regression ,medicine.disease_cause ,Comorbidities ,Direct acting antivirals ,HCV Cohort ,Linked-to-care patients ,Aged ,Antiviral Agents ,Coinfection ,Female ,Hepatitis C, Chronic ,Humans ,Italy ,Middle Aged ,Transients and Migrants ,0302 clinical medicine ,Medicine ,Chronic ,Gastroenterology ,virus diseases ,Hepatitis C ,Life evaluation ,030220 oncology & carcinogenesis ,Cohort ,030211 gastroenterology & hepatology ,Comorbiditie ,Human ,Hepatitis C virus ,Settore MED/12 - GASTROENTEROLOGIA ,03 medical and health sciences ,Disease severity ,Antiviral Agent ,Hepaciviru ,Hepatology ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,medicine.disease ,digestive system diseases ,Direct acting antiviral ,business ,Demography - Abstract
Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.
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- 2021
26. Real-world experience with obeticholic acid in patients with primary biliary cholangitis
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Anna Morgando, Mauro Viganò, Ana Lleo, Maurizio Pompili, Elisabetta De Gasperi, Daphne D’Amato, Alessandro Mussetto, Nora Cazzagon, Pietro Invernizzi, Francesca Colapietro, Vincenzo Ronca, Sara Labanca, Ester Vanni, M.R. Cannavò, Francesco Losito, Ernesto Claar, G. Scifo, Giovanni Galati, Umberto Vespasiani-Gentilucci, Silvia Storato, Alessio Gerussi, Grazia Anna Niro, Antonio Izzi, Barbara Omazzi, Antonio De Vincentis, Valentina Feletti, Giuseppe Grassi, Valeria Pace Palitti, Clara Mancuso, Vincenza Calvaruso, Evelise Frazzetto, Roberto Boldizzoni, Marco Marzioni, Floriano Rosina, Andrea Palermo, Antonino Picciotto, Valentina Bellia, Gaetano Bertino, Italian Pbc Registry, Guido Poggi, Rodolfo Sacco, Domenico Alvaro, Luigi Muratori, Maria Vinci, Marie Graciella Pigozzi, Raffaele Cozzolongo, Natalia Terreni, Annarosa Floreani, Maurizio Russello, Marco Distefano, Rinaldo Pellicano, Maria D'Antò, Marco Carbone, Rosanna Venere, R. Fontana, Antonio Picardi, Silvia Casella, S. E. O'Donnell, Federica Malinverno, Stefano Fagiuoli, Laura Cristoferi, Luchino Chessa, Giacomo Mulinacci, Pietro Pozzoni, Antonino Castellaneta, Giulia Marconi, Adriano M. Pellicelli, Francesca Romana Ponziani, Leonardo Baiocchi, D'Amato, D, De Vincentis, A, Malinverno, F, Vigano, M, Alvaro, D, Pompili, M, Picciotto, A, Palitti, V, Russello, M, Storato, S, Pigozzi, M, Calvaruso, V, De Gasperi, E, Lleo, A, Castellaneta, A, Pellicelli, A, Cazzagon, N, Floreani, A, Muratori, L, Fagiuoli, S, Niro, G, Feletti, V, Cozzolongo, R, Terreni, N, Marzioni, M, Pellicano, R, Pozzoni, P, Baiocchi, L, Chessa, L, Rosina, F, Bertino, G, Vinci, M, Morgando, A, Vanni, E, Scifo, G, Sacco, R, D'Anto, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, Cristoferi, L, Gerussi, A, Ronca, V, Venere, R, Ponziani, F, Cannavo, M, Mussetto, A, Fontana, R, Losito, F, Frazzetto, E, Distefano, M, Colapietro, F, Labanca, S, Marconi, G, Grassi, G, Galati, G, O'Donnell, S, Mancuso, C, Mulinacci, G, Palermo, A, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Carbone, M, Vespasiani-Gentilucci, U, D'Amato D, De Vincentis A, Malinverno F, Viganò M, Alvaro D, Pompili M, Picciotto A, Palitti VP, Russello M, Storato S, Pigozzi MG, Calvaruso V, De Gasperi E, Lleo A, Castellaneta A, Pellicelli A, Cazzagon N, Floreani A, Muratori L, Fagiuoli S, Niro GA, Feletti V, Cozzolongo R, Terreni N, Marzioni M, Pellicano R, Pozzoni P, Baiocchi L, Chessa L, Rosina F, Bertino G, Vinci M, Morgando A, Vanni E, Scifo G, Sacco R, D'Antò M, Bellia V, Boldizzoni R, Casella S, Omazzi B, Poggi G, Cristoferi L, Gerussi A, Ronca V, Venere R, Ponziani F, Cannavò M, Mussetto A, Fontana R, Losito F, Frazzetto E, Distefano M, Colapietro F, Labanca S, Marconi G, Grassi G, Galati G, O'Donnell SE, Mancuso C, Mulinacci G, Palermo A, Claar E, Izzi A, Picardi A, Invernizzi P, Carbone M, Vespasiani-Gentilucci U, and Italian PBC Registry and the Club Epatologi Ospedalieri (CLEO)/Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) PBC Study Group.
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upper limit of normal ,Cirrhosis ,ALT ,AMA ,Autoimmunity ,antinuclear antibodies ,ULN ,PBC ,Gastroenterology ,UDCA ,Settore MED/12 ,ULN, upper limit of normal ,obeticholic acid ,aRR, adjusted risk ratio ,CRFs, case record form ,AST, aspartate transferase ,Clinical endpoint ,GGT, gamma-glutamyl transferase ,QC ,primary biliary cholangitis ,Ursodeoxycholic acid ,ANA ,TCC ,Cholestasi ,TIPS ,Treatment Completer Cohort ,ANA, antinuclear antibodie ,medicine.medical_specialty ,RR ,UDCA, ursodeoxycholic acid ,TIPS, transjugular intrahepatic portosystemic shunt ,OCA ,Cirrhosi ,ALP, alkaline phosphatase ,autoimmune hepatitis ,medicine.disease ,digestive system diseases ,Discontinuation ,Keywords: AIH, autoimmune hepatiti ,QC, quality control ,chemistry ,gamma-glutamyl transferase ,randomised controlled trial ,electronic data capture ,antimitochondrial antibodies ,aspartate transferase ,Autoimmune hepatitis ,chemistry.chemical_compound ,AIH ,CRFs ,Immunology and Allergy ,adjusted risk ratio ,ANA, antinuclear antibodies ,RR, risk ratio ,Overall cohort ,ALT, alanine transferase ,AMA, antimitochondrial antibodie ,Cholestasis ,CRFs, case record forms ,Obeticholic acid ,Overlap PBC-AIH ,ursodeoxycholic acid ,OCA, obeticholic acid ,Tolerability ,alkaline phosphatase ,RCT ,Research Article ,medicine.drug ,case record forms ,Context (language use) ,AMA, antimitochondrial antibodies ,Internal medicine ,EDC, electronic data capture ,transjugular intrahepatic portosystemic shunt ,Internal Medicine ,medicine ,RCT, randomised controlled trial ,OC ,lcsh:RC799-869 ,quality control ,alanine transferase ,AST ,aRR ,Hepatology ,business.industry ,AIH, autoimmune hepatitis ,TCC, Treatment Completer Cohort ,PBC, primary biliary cholangiti ,GGT ,risk ratio ,OC, Overall cohort ,ALP ,lcsh:Diseases of the digestive system. Gastroenterology ,PBC, primary biliary cholangitis ,business ,EDC - Abstract
Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.
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- 2021
27. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
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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. 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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., Battezzati P.M., Crosignani A., Zuin M., Mattalia A., Calvaruso V., Colombo S., Benedetti A., Marzioni M., Galli A., Marra F., Tarocchi M., Picciotto A., Morisco F., Fabris L., Croce L.S., Tiribelli C., Toniutto P., Strazzabosco M., Ch'ng C.L., Rahman M., Yapp T., Sturgess R., Healey C., Czajkowski M., Gunasekera A., Gyawali P., Premchand P., Kapur K., Marley R., Foster G., Watson A., Dias A., Subhani J., Harvey R., McCorry R., Ramanaden D., Gasem J., Evans R., Mathialahan T., Shorrock C., Lipscomb G., Southern P., Tibble J., Gorard D., Palegwala A., Jones S., Dawwas M., Alexander G., Dolwani S., Prince M., Foxton M., Elphick D., Mitchison H., Gooding I., Karmo M., Saksena S., Mendall M., Patel M., Ede R., Austin A., Sayer J., Hankey L., Hovell C., Fisher N., Carter M., Koss K., Piotrowicz A., Grimley C., Neal D., Lim G., Levi S., Ala A., Broad A., Saeed A., Wood G., Brown J., Wilkinson M., Gordon H., Ramage J., Ridpath J., Ngatchu T., Grover B., Shaukat S., Shidrawi R., Abouda G., Ali F., Rees I., Salam I., Narain M., Brown A., Taylor-Robinson S., Williams S., Grellier L., Banim P., Das D., Chilton A., Heneghan M., Curtis H., Gess M., Drake I., Aldersley M., Davies M., Jones R., McNair A., Srirajaskanthan R., Pitcher M., Sen S., Bird G., Barnardo A., Kitchen P., Yoong K., Chirag O., Sivaramakrishnan N., MacFaul G., Jones D., Shah A., Evans C., Saha S., Pollock K., Bramley P., Mukhopadhya A., Fraser A., Mills P., Shallcross C., Campbell S., Bathgate A., Shepherd A., Dillon J., Rushbrook S., Przemioslo R., Macdonald C., Metcalf J., Shmueli U., Davis A., Naqvi A., Lee T., Ryder S.D., Collier J., Klass H., Ninkovic M., Cramp M., Sharer N., Aspinall R., Goggin P., Ghosh D., Douds A., Hoeroldt B., Booth J., Williams E., Hussaini H., Stableforth W., Ayres R., Thorburn D., Marshall E., Burroughs A., Mann S., Lombard M., Richardson P., Patanwala I., Maltby J., Brookes M., Mathew R., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Panter S., Shearman J., Bray G., Butcher G., Forton D., Mclindon J., Cowan M., Whatley G., Mandal A., Gupta H., Sanghi P., Jain S., Pereira S., Prasad G., Watts G., Wright M., Neuberger J., Gordon F., Unitt E., Grant A., Delahooke T., Higham A., Brind A., Cox M., Ramakrishnan S., King A., Collins C., Whalley S., Li A., Fraser J., Bell A., Wong V.S., Singhal A., Gee I., Ang Y., Ransford R., Gotto J., Millson C., Bowles J., Thomas C., Harrison M., Galaska R., Kendall J., Whiteman J., Lawlor C., Gray C., Elliott K., Mulvaney-Jones C., Hobson L., Van Duyvenvoorde G., Loftus A., Seward K., Penn R., Maiden J., Damant R., Hails J., Cloudsdale R., Silvestre V., Glenn S., Dungca E., Wheatley N., Doyle H., Kent M., Hamilton C., Braim D., Wooldridge H., Abrahams R., Paton A., Lancaster N., Gibbins A., Hogben K., Desousa P., Muscariu F., Musselwhite J., McKay A., Tan L., Foale C., Brighton J., Flahive K., Nambela E., Townshend P., Ford C., Holder S., Palmer C., Featherstone J., Nasseri M., Sadeghian J., Williams B., Rolls S.-A., Hynes A., Duggan C., Crossey M., Stansfield G., MacNicol C., Wilkins J., Wilhelmsen E., Raymode P., Lee H.-J., Durant E., Bishop R., Ncube N., Tripoli S., Casey R., Cowley C., Miller R., Houghton K., Ducker S., Wright F., Bird B., Baxter G., Keggans J., Hughes M., Grieve E., Young K., Williams D., Ocker K., Hines F., Martin K., Innes C., Valliani T., Fairlamb H., Thornthwaite S., Eastick A., Tanqueray E., Morrison J., Holbrook B., Browning J., Walker K., Congreave S., Verheyden J., Slininger S., Stafford L., O'Donnell D., Ainsworth M., Lord S., Kent L., March L., Dickson C., Simpson D., Longhurst B., Hayes M., Shpuza E., White N., Besley S., Pearson S., Wright A., Jones L., Gunter E., Dewhurst H., Fouracres A., Farrington L., Graves L., Marriott S., Leoni M., Tyrer D., Dali-kemmery L., Lambourne V., Green M., Sirdefield D., Amor K., Colley J., Shinder B., Jones J., Mills M., Carnahan M., Taylor N., Boulton K., Tregonning J., Brown C., Clifford G., Archer E., Hamilton M., Curtis J., Shewan T., Walsh S., Warner K., Netherton K., Mupudzi M., Gunson B., Gitahi J., Gocher D., Batham S., Pateman H., Desmennu S., Conder J., Clement D., Gallagher S., Orpe J., Chan P., Currie L., O'Donohoe L., Oblak M., Morgan L., Quinn M., Amey I., Baird Y., Cotterill D., Cumlat L., Winter L., Greer S., Spurdle K., Allison J., Dyer S., Sweeting H., Kordula J., Aiba Y., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Kawai Y., Kohn S.-S., Gervais O., Migita K., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Higuchi N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Takikawa H., Ohira H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Carbone M., Cardamone G., Duga S., Gershwin M.E., Seldin M.F., Invernizzi P., Asselta, R, Paraboschi, E, Gerussi, A, Cordell, H, Mells, G, Sandford, R, Jones, D, Nakamura, M, Ueno, K, Hitomi, Y, Kawashima, M, Nishida, N, Tokunaga, K, Nagasaki, M, Tanaka, A, Tang, R, Li, Z, Shi, Y, Liu, X, Xiong, M, Hirschfield, G, Siminovitch, K, Walker, E, Xie, G, Mason, A, Myers, R, Peltekian, K, Ghent, C, Atkinson, E, Juran, B, Lazaridis, K, Lu, Y, Gu, X, Jing, K, Amos, C, Affronti, A, Brunetto, M, Coco, B, Spinzi, G, Elia, G, Ferrari, C, Lleo, A, Muratori, L, Muratori, P, Portincasa, P, Colli, A, Bruno, S, Colloredo, G, Azzaroli, F, Andreone, P, Bragazzi, M, Alvaro, D, Cardinale, V, Cazzagon, N, Rigamonti, C, Floreani, A, Rosina, F, Ciaccio, A, Cristoferi, L, D'Amato, D, Malinverno, F, Mancuso, C, Massironi, S, Milani, C, O'Donnell, S, Ronca, V, Barisani, D, Lampertico, P, Donato, F, Fagiuoli, S, Almasio, P, Giannini, E, Cursaro, C, Colombo, M, Valenti, L, Miele, L, Andriulli, A, Niro, G, Grattagliano, I, Morini, L, Casella, G, Vinci, M, Battezzati, P, Crosignani, A, Zuin, M, Mattalia, A, Calvaruso, V, Colombo, S, Benedetti, A, Marzioni, M, Galli, A, Marra, F, Tarocchi, M, Picciotto, A, Morisco, F, Fabris, L, Croce, L, Tiribelli, C, Toniutto, P, Strazzabosco, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Dawwas, M, Alexander, G, Dolwani, S, Prince, M, Foxton, M, Elphick, D, Mitchison, H, Gooding, I, Karmo, M, Saksena, S, Mendall, M, Patel, M, Ede, R, Austin, A, Sayer, J, Hankey, L, Hovell, C, Fisher, N, Carter, M, Koss, K, Piotrowicz, A, Grimley, C, Neal, D, Lim, G, Levi, S, Ala, A, Broad, A, Saeed, A, Wood, G, Brown, J, Wilkinson, M, Gordon, H, Ramage, J, Ridpath, J, Ngatchu, T, Grover, B, Shaukat, S, Shidrawi, R, Abouda, G, Ali, F, Rees, I, Salam, I, Narain, M, Brown, A, Taylor-Robinson, S, Williams, S, Grellier, L, Banim, P, Das, D, Chilton, A, Heneghan, M, Curtis, H, Gess, M, Drake, I, Aldersley, M, Davies, M, Jones, R, Mcnair, A, Srirajaskanthan, R, Pitcher, M, Sen, S, Bird, G, Barnardo, A, Kitchen, P, Yoong, K, Chirag, O, Sivaramakrishnan, N, Macfaul, G, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Fraser, A, Mills, P, Shallcross, C, Campbell, S, Bathgate, A, Shepherd, A, Dillon, J, Rushbrook, S, Przemioslo, R, Macdonald, C, Metcalf, J, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Ninkovic, M, Cramp, M, Sharer, N, Aspinall, R, Goggin, P, Ghosh, D, Douds, A, Hoeroldt, B, Booth, J, Williams, E, Hussaini, H, Stableforth, W, Ayres, R, Thorburn, D, Marshall, E, Burroughs, A, Mann, S, Lombard, M, Richardson, P, Patanwala, I, Maltby, J, Brookes, M, Mathew, R, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Panter, S, Shearman, J, Bray, G, Butcher, G, Forton, D, Mclindon, J, Cowan, M, Whatley, G, Mandal, A, Gupta, H, Sanghi, P, Jain, S, Pereira, S, Prasad, G, Watts, G, Wright, M, Neuberger, J, Gordon, F, Unitt, E, Grant, A, Delahooke, T, Higham, A, Brind, A, Cox, M, Ramakrishnan, S, King, A, Collins, C, Whalley, S, Li, A, Fraser, J, Bell, A, Wong, V, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney-Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali-kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, Kordula, J, Aiba, Y, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Kawai, Y, Kohn, S, Gervais, O, Migita, K, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Higuchi, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Takikawa, H, Ohira, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Carbone, M, Cardamone, G, Duga, S, Gershwin, M, Seldin, M, Invernizzi, P, Asselta R, Paraboschi EM, Gerussi A, Cordell HJ, Mells GF, Sandford RN, Jones DE, 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 KA, Canadian-US PBC Consortium, Italian 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
28. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs
- Author
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Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .
- Subjects
Liver Cirrhosis ,ALSPAC ,ERN RARE-LIVER ,Genomic co-localization ,Network-based in silico drug efficacy screening ,UK-PBC ,0301 basic medicine ,Candidate gene ,Genome-Wide Association Study ,Humans ,Liver Cirrhosis, Biliary ,Italian PBC Study Group ,LD SCORE REGRESSION ,Japan-PBC-GWAS Consortium ,Genome-wide association study ,Locus (genetics) ,Disease ,SUSCEPTIBILITY ,PBC ,Chronic liver disease ,Bioinformatics ,GENETIC ASSOCIATION ,1117 Public Health and Health Services ,03 medical and health sciences ,0302 clinical medicine ,UK-PBC Consortium ,Genotype ,Medicine ,Genetic association ,Science & Technology ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Biliary ,Chinese PBC Consortium ,1103 Clinical Sciences ,medicine.disease ,PBC Consortia ,030104 developmental biology ,Meta-analysis ,ERN RARE LIVER ,030211 gastroenterology & hepatology ,US PBC Consortium ,Canadian PBC Consortium ,business ,Life Sciences & Biomedicine ,Human - Abstract
[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.
- Published
- 2021
29. International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
- Author
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Cordell, Heather J., Younghun, Han, Mells, George F., Yafang, Li, Hirschfield, Gideon M., Greene, Casey S., Gang, Xie, Juran 7, Brian D., Dakai Zhu, 2, Qian 2, David C., Floyd, James A. B., Morley, Katherine I., Daniele Prati 11, Ana Lleo 12, Daniele, Cusi, Eric Gershwin 15, M., Anderson 8, Carl A., Lazaridis 7, Konstantinos N., Pietro, Invernizzi, Seldin 15, Michael F., Sandford, Richard N., Amos 2, Christopher I., Siminovitch, Katherine A., Schlicht 7, Erik M., Craig Lammert, 7, Atkinson 19, Elizabeth J., Chan 19, Landon L., Mariza de Andrade 19, Tobias Balschun 20, Mason 21, Andrew L., Myers 22, Robert P., Jinyi Zhang 23, Piotr Milkiewicz 24, Jia Qu 25, Odin 26, Joseph A., Luketic 27, Velimir A., Bacon 28, Bruce R., Bodenheimer Jr 29, Henry C., Valentina Liakina 30, Catherine Vincent 31, Cynthia Levy 32, Gregersen, Peter K., Almasio, 33 Piero L., Domenico Alvaro 35, Pietro Andreone 36, Angelo Andriulli 37, Cristina Barlassina 38, Pier Maria Battezzati 39, Antonio Benedetti 40, Francesca Bernuzzi 41, Ilaria Bianchi 41, Maria Consiglia Bragazzi 42, Maurizia Brunetto 43, Savino Bruno 41, Giovanni Casella 44, Barbara Coco 43, Agostino Colli 45, Massimo Colombo 46, Silvia Colombo 47, Carmela Cursaro 36, Lory Saveria Croce, ` 48, Andrea Crosignani 39, Maria Francesca Donato 46, Gianfranco Elia 49, Luca Fabris 50, Carlo Ferrari 49, Annarosa Floreani 51, Barbara Foglieni 11, Rosanna Fontana 37, Galli, Andrea, Roberta Lazzari 51, Fabio Macaluso 34, Federica Malinverno 46, Marra, Fabio, Marco Marzioni 40, Alberto Mattalia 54, Renzo Montanari 55, Lorenzo Morini 56, Filomena Morisco 57, Mousa Hani S., 41, Luigi Muratori 36, Paolo Muratori 36, Niro 37, Grazia A., Palmieri 58, Vincenzo O., Antonio Picciotto 59, Mauro Podda 41, Piero Portincasa 58, Vincenzo Ronca 41, Floriano Rosina 60, Sonia Rossi 41, Ilaria Sogno 41, Giancarlo Spinzi 61, Marta Spreafico 11, Mario, Strazzabosco, Sonia Tarallo 60, Tarocchi, Mirko, Claudio Tiribelli 48, Pierluigi Toniutto 64, Maria Vinci 65, Massimo, Zuin, Chin Lye Ch’ng, Mesbah Rahman 68, Tom Yapp 69, Richard Sturgess 70, Christopher Healey 71, Marek, Czajkowski, Anton, Gunasekera, Pranab Gyawali 77, Purushothaman Premchand 78, Kapil Kapur 79, Richard Marley 80, Graham Foster 80, Alan Watson 81, Aruna Dias 82, Javaid Subhani 83, Rory Harvey 84, Roger McCorry 85, David Ramanaden 86, Jaber Gasem 87, Richard Evans 88, Thiriloganathan Mathialahan 89, Christopher Shorrock 90, George Lipscomb 91, Paul Southern 92, Jeremy Tibble 93, David, Gorard, Altaf Palegwala 98, Susan, Jones, Marco Carbone 101, Mohamed Dawwas 101, Graeme Alexander 101, Sunil, Dolwani, Martin Prince 104, Matthew Foxton 105, David Elphick 106, Harriet Mitchison 107, Ian Gooding 108, Mazn Karmo 109, Sushma, Saksena, Mike, Mendall, Minesh, Patel, Roland, Ede, Andrew Austin 119, Joanna, Sayer, Lorraine Hankey 122, Christopher Hovell 122, Neil Fisher 123, Martyn, Carter, Konrad Koss 126, Andrzej, Piotrowicz, Charles, Grimley, David, Neal, Guan Lim 135, Sass, Levi, Aftab Ala 138, Andrea Broad 139, Athar Saeed 139, Gordon Wood 140, Jonathan, Brown, Mark, Wilkinson, Harriet Gordon 145, John Ramage 146, Jo Ridpath 147, Theodore, Ngatchu, Bob Grover 151, Syed Shaukat 152, Ray Shidrawi 153, George, Abouda, Faiz Ali 156, Ian Rees 157, Imroz Salam 158, Mark Narain 159, Ashley, Brown, Simon Taylor Robinson 162, Simon Williams 163, Leonie Grellier 164, Paul Banim 165, Debasish Das 166, Andrew Chilton 166, Michael Heneghan 167, Howard, Curtis, Markus Gess 170, Ian, Drake, Mark, Aldersley, Mervyn, Davies, Rebecca, Jones, Alastair McNair 175, Raj Srirajaskanthan 176, Maxton, Pitcher, Sambit Sen 179, George, Bird, Adrian Barnardo 182, Paul Kitchen 182, Kevin Yoong 183, Oza, Chirag, Nurani Sivaramakrishnan 186, George MacFaul 187, David Jones 188, Amir Shah 189, Chris Evans 190, Subrata Saha 191, Katharine, Pollock, Peter, Bramley, Ashis, Mukhopadhya, Andrew, Fraser, Peter, Mills, Christopher, Shallcross, Stewart, Campbell, Andrew, Bathgate, Alan Shepherd 213, John Dillon 214, Simon Rushbrook 215, Robert Przemioslo 216 Christopher Macdonald, Jane, Metcalf, Udi Shmueli 221, Andrew, Davis, Asifabbas, Naqvi, Tom, Lee, Ryder, Stephen D., Jane Collier 231, Howard, Klass, Mary, Ninkovic, Matthew Cramp 238, Nicholas Sharer 239, Richard Aspinall 240, Patrick Goggin 240, Deb, Ghosh, Andrew Douds 243, Barbara Hoeroldt 244, Jonathan Booth 245, Earl Williams 246, Hyder Hussaini 247, William Stableforth 247, Reuben Ayres 248, Douglas Thorburn 249, Eileen Marshall 249, Andrew Burroughs 249, Steven, Mann, Martin Lombard 252, Paul Richardson 252, Imran Patanwala 252, Julia Maltby 253, Matthew Brookes 254, Ray, Mathew, Samir Vyas 257, Saket Singhal 258, Dermot, Gleeson, Sharat, Misra, Jeff, Butterworth, Keith George 265, Tim, Harding, Andrew, Douglass, Simon Panter 270, Jeremy Shearman 271, Gary Bray 272, Graham, Butcher, Daniel Forton 275, John, Mclindon, Matthew Cowan 279, Gregory Whatley 280, Aditya, Mandal, Hemant, Gupta, Pradeep, Sanghi, Sanjiv Jain 283, Steve Pereira 284, Geeta Prasad 285, Gill Watts 285, Mark Wright 286, James Neuberger 287, Fiona Gordon 288, Esther Unitt 289, Allister, Grant, Toby, Delahooke, Andrew Higham 293, Alison Brind 294, Mark Cox 295, Subramaniam Ramakrishnan 296, Alistair, King, Carole Collins 300, Simon, Whalley, Andy Li 303, Jocelyn Fraser 304, Andrew Bell 305, Voi Shim Wong 306, Amit, Singhal, Ian, Gee, Yeng Ang 312, Rupert Ransford 313, James Gotto 314, Charles, Millson, Jane Bowles 318, Caradog, Thomas, Melanie Harrison 70, Roman Galaska 71, Jennie, Kendall, Jessica, Whiteman, Caroline, Lawlor, Catherine, Gray, Keith Elliott 79, Caroline Mulvaney Jones, Lucie, Hobson, Greta Van Duyvenvoorde 90, Alison Loftus 91, Katie Seward 92, Ruth, Penn, Jane Maiden 98, Rose Damant 98, Janeane Hails 101, Rebecca, Cloudsdale, Valeria Silvestre 105, Sue Glenn 106, Eleanor Dungca 107, Natalie Wheatley 108, Helen Doyle 109, Melanie, Kent, Caroline, Hamilton, Delyth, Braim, Helen Wooldridge 117, Rachel Abrahams 117, Alison Paton 119, Nicola, Lancaster, Andrew Gibbins 122, Karen Hogben 122, Phillipa, Desousa, Florin, Muscariu, Janine, Musselwhite, Alexandra McKay 132, LaiTing Tan 135, Carole Foale 138, Jacqueline Brighton 138, Kerry Flahive 140, Estelle, Nambela, Paula, Townshend, Chris, Ford, Sophie, Holder, Caroline, Palmer, James Featherstone 147, Mariam Nasseri 151, Joy Sadeghian 153, Bronwen, Williams, Carol Thomas 156, Sally Ann Rolls 156, Abigail Hynes 159, Claire Duggan 159, Sarah Jones 159, Mary, Crossey, Glynis Stansfield 163, Carolyn MacNicol 163, Joy Wilkins 164, Elva Wilhelmsen 165, Parizade Raymode 166, Hye Jeong Lee 167, Emma, Durant, Rebecca, Bishop, Noma, Ncube, Sherill, Tripoli, Rebecca, Casey, Caroline Cowley 182, Richard Miller 183, Kathryn Houghton 188, Samantha Ducker 188, Fiona Wright 189, Bridget Bird 191, Gwen Baxter 191, Janie Keggans 191, Maggie, Hughes, Emma Grieve 196, Karin Young 196, Williams 197, D., Kate Ocker 199, Frances, Hines, Kirsty, Martin, Caron, Innes, Talal Valliani 216, Helen, Fairlamb, Sarah, Thornthwaite, Anne, Eastick, Elizabeth Tanqueray 221, Jennifer Morrison 222, Becky Holbrook 222, Julie, Browning, Kirsten, Walker, Susan, Congreave, Juliette, Verheyden, Susan, Slininger, Lizzie Stafford 231, Denise O’Donnell 231, Mark Ainsworth 231, Susan Lord 118, Linda, Kent, Linda March 238, Christine Dickson 239, Diane Simpson 239, Beverley Longhurst 240, Maria Hayes 240, Ervin, Shpuza, Nikki, White, Sarah, Besley, Sallyanne Pearson 244, Alice Wright 245, Linda Jones 245, Emma Gunter 246, Hannah Dewhurst 246, Anna Fouracres 247, Liz Farrington 247, Lyn Graves 247, Suzie Marriott 248, Marina Leoni 249, David Tyrer 252, Kate Martin 252, Lola Dali kemmery 253, Victoria Lambourne 253, Marie Green 254, Dawn, Sirdefield, Kelly Amor 255, Julie Colley 258, Bal Shinder 258, Jayne Jones 260, Marisa Mills 260, Mandy, Carnahan, Natalie Taylor 265, Kerenza Boulton 265, Julie, Tregonning, Carly Brown 270, Gayle Clifford 270, Emily Archer 271, Maria, Hamilton, Janette Curtis 278, Tracey Shewan 279, Sue Walsh 280, Karen, Warner, Kimberley Netherton 283, Mcdonald Mupudzi 286, Bridget Gunson 287, Jane Gitahi 288, Denise Gocher 289, Sally, Batham, Hilary, Pateman, Senayon, Desmennu, Jill Conder 293, Darren Clement 294, Susan Gallagher 294, Jacky Orpe 256, PuiChing Chan 296, Lynn, Currie, Lynn, O’Donohoe, Metod Oblak 300, Lisa Morgan 302, Marie Quinn 303, Isobel Amey 304, Yolanda Baird 304, Donna Cotterill 305, Lourdes Cumlat 306, Louise Winter 312, Sandra Greer 312, Katie, Spurdle, Joanna, Allison, Simon, Dyer, Helen, Sweeting, Jean, Kordula, Cordell, H. J., Han, Y., Mells, G. F., Li, Y., Hirschfield, G. M., Greene, C. S., Xie, G., Juran, B. D., Zhu, D., Qian, D. C., Floyd, J. A. B., Morley, K. I., Prati, D., Lleo, A., Cusi, D., Gershwin, M. E., Anderson, C. A., Lazaridis, K. N., Invernizzi, P., Seldin, M. F., Sandford, R. N., Amos, C. I., Siminovitch, K. A., Schlicht, E. M., Lammert, C., Atkinson, E. J., Chan, L. L., De Andrade, M., Balschun, T., Mason, A. L., Myers, R. P., Zhang, J., Milkiewicz, P., Qu, J., Odin, J. A., Luketic, V. A., Bacon, B. R., Bodenheimer, H. C., Liakina, V., Vincent, C., Levy, C., Gregersen, P. K., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Barlassina, C., Battezzati, P. M., Benedetti, A., Bernuzzi, F., Bianchi, I., Bragazzi, M. C., Brunetto, M., Bruno, S., Casella, G., Coco, B., Colli, A., Colombo, M., Colombo, S., Cursaro, C., Croce, L. S., Crosignani, A., Donato, M. F., Elia, G., Fabris, L., Ferrari, C., Floreani, A., Foglieni, B., Fontana, R., Galli, A., Lazzari, R., Macaluso, F., Malinverno, F., Marra, F., Marzioni, M., Mattalia, A., Montanari, R., Morini, L., Morisco, F., Mousa Hani, S., Muratori, L., Muratori, P., Niro, G. A., Palmieri, V. O., Picciotto, A., Podda, M., Portincasa, P., Ronca, V., Rosina, F., Rossi, S., Sogno, I., Spinzi, G., Spreafico, M., Strazzabosco, M., Tarallo, S., Tarocchi, M., Tiribelli, C., Toniutto, P., Vinci, M., Zuin, 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., Carbone, M., 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., Stephen, 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., Cordell, Heather J, Han, Younghun, Mells, George F., Li, Yafang, Hirschfield, Gideon M., Greene, Casey S., Xie, Gang, Juran, Brian D., Zhu, Dakai, Qian, David C., Floyd, James A. B., Morley, Katherine I., Prati, Daniele, Lleo, Ana, Cusi, Daniele, Gershwin, M. Eric, Anderson, Carl A., Lazaridis, Konstantinos N., Invernizzi, Pietro, Seldin, Michael F., Sandford, Richard N., Amos, Christopher I., Siminovitch, Katherine A., Schlicht, Erik M., Lammert, Craig, Atkinson, Elizabeth J., Chan, Landon L., De Andrade, Mariza, Balschun, Tobia, Mason, Andrew L., Myers, Robert P., Zhang, Jinyi, Milkiewicz, Piotr, Qu, Jia, Odin, Joseph A., Luketic, Velimir A., Bacon, Bruce R., Bodenheimer, Henry C., Liakina, Valentina, Vincent, Catherine, Levy, Cynthia, Gregersen, Peter K., Almasio, Piero L., Alvaro, Domenico, Andreone, Pietro, Andriulli, Angelo, Barlassina, Cristina, Battezzati, Pier Maria, Benedetti, Antonio, Bernuzzi, Francesca, Bianchi, Ilaria, Bragazzi, Maria Consiglia, Brunetto, Maurizia, Bruno, Savino, Casella, Giovanni, Coco, Barbara, Colli, Agostino, Colombo, Massimo, Colombo, Silvia, Cursaro, Carmela, Crocè, Lory Saveria, Crosignani, Andrea, Donato, Maria Francesca, Elia, Gianfranco, Fabris, Luca, Ferrari, Carlo, Floreani, Annarosa, Foglieni, Barbara, Fontana, Rosanna, Galli, Andrea, Lazzari, Roberta, Macaluso, Fabio, Malinverno, Federica, Marra, Fabio, Marzioni, Marco, Mattalia, Alberto, Montanari, Renzo, Morini, Lorenzo, Morisco, Filomena, Muratori, Luigi, Muratori, Paolo, Niro, Grazia A., Palmieri, Vincenzo O., Picciotto, Antonio, Podda, Mauro, Portincasa, Piero, Ronca, Vincenzo, Rosina, Floriano, Rossi, Sonia, Sogno, Ilaria, Spinzi, Giancarlo, Spreafico, Marta, Strazzabosco, Mario, Tarallo, Sonia, Tarocchi, Mirko, Tiribelli, Claudio, Toniutto, Pierluigi, Vinci, Maria, Zuin, Massimo, Ch'Ng, Chin Lye, Rahman, Mesbah, Yapp, Tom, Sturgess, Richard, Healey, Christopher, Czajkowski, Marek, Gunasekera, Anton, Gyawali, Pranab, Premchand, Purushothaman, Kapur, Kapil, Marley, Richard, Foster, Graham, Watson, Alan, Dias, Aruna, Subhani, Javaid, Harvey, Rory, Mccorry, Roger, Ramanaden, David, Gasem, Jaber, Evans, Richard, Mathialahan, Thiriloganathan, Shorrock, Christopher, Lipscomb, George, Southern, Paul, Tibble, Jeremy, Gorard, David, Palegwala, Altaf, Jones, Susan, Carbone, Marco, Dawwas, Mohamed, Alexander, Graeme, Dolwani, Sunil, Prince, Martin, Foxton, Matthew, Elphick, David, Mitchison, Harriet, Gooding, Ian, Karmo, Mazn, Saksena, Sushma, Mendall, Mike, Patel, Minesh, Ede, Roland, Austin, Andrew, Sayer, Joanna, Hankey, Lorraine, Hovell, Christopher, Fisher, Neil, Carter, Martyn, Koss, Konrad, Piotrowicz, Andrzej, Grimley, Charle, Neal, David, Lim, Guan, Levi, Sa, Ala, Aftab, Broad, Andrea, Saeed, Athar, Wood, Gordon, Brown, Jonathan, Wilkinson, Mark, Gordon, Harriet, Ramage, John, Ridpath, Jo, Ngatchu, Theodore, Grover, Bob, Shaukat, Syed, Shidrawi, Ray, Abouda, George, Ali, Faiz, Rees, Ian, Salam, Imroz, Narain, Mark, Brown, Ashley, Taylor-Robinson, Simon, Williams, Simon, Grellier, Leonie, Banim, Paul, Das, Debasish, Chilton, Andrew, Heneghan, Michael, Curtis, Howard, Gess, Marku, Drake, Ian, Aldersley, Mark, Davies, Mervyn, Jones, Rebecca, Mcnair, Alastair, Srirajaskanthan, Raj, Pitcher, Maxton, Sen, Sambit, Bird, George, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Chirag, Oza, Sivaramakrishnan, Nurani, Macfaul, George, Jones, David, Shah, Amir, Evans, Chri, Saha, Subrata, Pollock, Katharine, Bramley, Peter, Mukhopadhya, Ashi, Fraser, Andrew, Mills, Peter, Shallcross, Christopher, Campbell, Stewart, Bathgate, Andrew, Shepherd, Alan, Dillon, John, Rushbrook, Simon, Przemioslo, Robert, Macdonald, Christopher, Metcalf, Jane, Shmueli, Udi, Davis, Andrew, Naqvi, Asifabba, Lee, Tom, Stephen, Dyder, Collier, Jane, Klass, Howard, Ninkovic, Mary, Cramp, Matthew, Sharer, Nichola, Aspinall, Richard, Goggin, Patrick, Ghosh, Deb, Douds, Andrew, Hoeroldt, Barbara, Booth, Jonathan, Williams, Earl, Hussaini, Hyder, Stableforth, William, Ayres, Reuben, Thorburn, Dougla, Marshall, Eileen, Burroughs, Andrew, Mann, Steven, Lombard, Martin, Richardson, Paul, Patanwala, Imran, Maltby, Julia, Brookes, Matthew, Mathew, Ray, Vyas, Samir, Singhal, Saket, Gleeson, Dermot, Misra, Sharat, Butterworth, Jeff, George, Keith, Harding, Tim, Douglass, Andrew, Panter, Simon, Shearman, Jeremy, Bray, Gary, Butcher, Graham, Forton, Daniel, Mclindon, John, Cowan, Matthew, Whatley, Gregory, Mandal, Aditya, Gupta, Hemant, Sanghi, Pradeep, Jain, Sanjiv, Pereira, Steve, Prasad, Geeta, Watts, Gill, Wright, Mark, Neuberger, Jame, Gordon, Fiona, Unitt, Esther, Grant, Allister, Delahooke, Toby, Higham, Andrew, Brind, Alison, Cox, Mark, Ramakrishnan, Subramaniam, King, Alistair, Collins, Carole, Whalley, Simon, Li, Andy, Fraser, Jocelyn, Bell, Andrew, Wong, Voi Shim, Singhal, Amit, Gee, Ian, Ang, Yeng, Ransford, Rupert, Gotto, Jame, Millson, Charle, Bowles, Jane, Thomas, Caradog, Harrison, Melanie, Galaska, Roman, Kendall, Jennie, Whiteman, Jessica, Lawlor, Caroline, Gray, Catherine, Elliott, Keith, Mulvaney-Jones, Caroline, Hobson, Lucie, Van Duyvenvoorde, Greta, Loftus, Alison, Seward, Katie, Penn, Ruth, Maiden, Jane, Damant, Rose, Hails, Janeane, Cloudsdale, Rebecca, Silvestre, Valeria, Glenn, Sue, Dungca, Eleanor, Wheatley, Natalie, Doyle, Helen, Kent, Melanie, Hamilton, Caroline, Braim, Delyth, Wooldridge, Helen, Abrahams, Rachel, Paton, Alison, Lancaster, Nicola, Gibbins, Andrew, Hogben, Karen, Desousa, Phillipa, Muscariu, Florin, Musselwhite, Janine, Mckay, Alexandra, Tan, Laiting, Foale, Carole, Brighton, Jacqueline, Flahive, Kerry, Nambela, Estelle, Townshend, Paula, Ford, Chri, Holder, Sophie, Palmer, Caroline, Featherstone, Jame, Nasseri, Mariam, Sadeghian, Joy, Williams, Bronwen, Thomas, Carol, Rolls, Sally-Ann, Hynes, Abigail, Duggan, Claire, Jones, Sarah, Crossey, Mary, Stansfield, Glyni, Macnicol, Carolyn, Wilkins, Joy, Wilhelmsen, Elva, Raymode, Parizade, Lee, Hye-Jeong, Durant, Emma, Bishop, Rebecca, Ncube, Noma, Tripoli, Sherill, Casey, Rebecca, Cowley, Caroline, Miller, Richard, Houghton, Kathryn, Ducker, Samantha, Wright, Fiona, Bird, Bridget, Baxter, Gwen, Keggans, Janie, Hughes, Maggie, Grieve, Emma, Young, Karin, Ocker, Kate, Hines, France, Martin, Kirsty, Innes, Caron, Valliani, Talal, Fairlamb, Helen, Thornthwaite, Sarah, Eastick, Anne, Tanqueray, Elizabeth, Morrison, Jennifer, Holbrook, Becky, Browning, Julie, Walker, Kirsten, Congreave, Susan, Verheyden, Juliette, Slininger, Susan, Stafford, Lizzie, O'Donnell, Denise, Ainsworth, Mark, Lord, Susan, Kent, Linda, March, Linda, Dickson, Christine, Simpson, Diane, Longhurst, Beverley, Hayes, Maria, Shpuza, Ervin, White, Nikki, Besley, Sarah, Pearson, Sallyanne, Wright, Alice, Jones, Linda, Gunter, Emma, Dewhurst, Hannah, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Marriott, Suzie, Leoni, Marina, Tyrer, David, Martin, Kate, Dali-Kemmery, Lola, Lambourne, Victoria, Green, Marie, Sirdefield, Dawn, Amor, Kelly, Colley, Julie, Shinder, Bal, Jones, Jayne, Mills, Marisa, Carnahan, Mandy, Taylor, Natalie, Boulton, Kerenza, Tregonning, Julie, Brown, Carly, Clifford, Gayle, Archer, Emily, Hamilton, Maria, Curtis, Janette, Shewan, Tracey, Walsh, Sue, Warner, Karen, Netherton, Kimberley, Mupudzi, Mcdonald, Gunson, Bridget, Gitahi, Jane, Gocher, Denise, Batham, Sally, Pateman, Hilary, Desmennu, Senayon, Conder, Jill, Clement, Darren, Gallagher, Susan, Orpe, Jacky, Chan, Puiching, Currie, Lynn, O'Donohoe, Lynn, Oblak, Metod, Morgan, Lisa, Quinn, Marie, Amey, Isobel, Baird, Yolanda, Cotterill, Donna, Cumlat, Lourde, Winter, Louise, Greer, Sandra, Spurdle, Katie, Allison, Joanna, Dyer, Simon, Sweeting, Helen, Kordula, Jean, Heather J., Cordell, Younghun, Han, George F., Mell, Yafang, Li, Gideon M., Hirschfield, Casey S., Greene, Gang, Xie, Brian D., Juran, Dakai, Zhu, David C., Qian, James A. B., Floyd, Katherine I., Morley, Daniele, Prati, Ana, Lleo, Daniele, Cusi, Canadian US PBC, Consortium, Italian PBC Genetics Study, Group, UK PBC, Consortium, M., Eric Gershwin, Carl A., Anderson, Konstantinos N., Lazaridi, Pietro, Invernizzi, Michael F., Seldin, Richard N., Sandford, Christopher I., Amo, Katherine A., Siminovitch, Cordell H.J., Han Y., Mells G.F., Li Y., Hirschfield G.M., Greene C.S., Xie G., Juran B.D., Zhu D., Qian D.C., Floyd J.A.B., Morley K.I., Prati D., Lleo A., Cusi D., Gershwin M.E., Anderson C.A., Lazaridis K.N., Invernizzi P., Seldin M.F., Sandford R.N., Amos C.I., Siminovitch K.A., Schlicht E.M., Lammert C., Atkinson E.J., Chan L.L., De Andrade M., Balschun T., Mason A.L., Myers R.P., Zhang J., Milkiewicz P., Qu J., Odin J.A., Luketic V.A., Bacon B.R., Bodenheimer H.C., Liakina V., Vincent C., Levy C., Gregersen P.K., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Barlassina C., Battezzati P.M., Benedetti A., Bernuzzi F., Bianchi I., Bragazzi M.C., Brunetto M., Bruno S., Casella G., Coco B., Colli A., Colombo M., Colombo S., Cursaro C., Croce L.S., Crosignani A., Donato M.F., Elia G., Fabris L., Ferrari C., Floreani A., Foglieni B., Fontana R., Galli A., Lazzari R., Macaluso F., Malinverno F., Marra F., Marzioni M., Mattalia A., Montanari R., Morini L., Morisco F., Mousa Hani S., Muratori L., Muratori P., Niro G.A., Palmieri V.O., Picciotto A., Podda M., Portincasa P., Ronca V., Rosina F., Rossi S., Sogno I., Spinzi G., Spreafico M., Strazzabosco M., Tarallo S., Tarocchi M., Tiribelli C., Toniutto P., Vinci M., Zuin 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., Carbone M., 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., Stephen 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., Cordell, H, Han, Y, Mells, G, Li, Y, Hirschfield, G, Greene, C, Xie, G, Juran, B, Zhu, D, Qian, D, Floyd, J, Morley, K, Prati, D, Lleo, A, Cusi, D, Gershwin, M, Anderson, C, Lazaridis, K, Invernizzi, P, Seldin, M, Sandford, R, Amos, C, Siminovitch, K, Schlicht, E, Lammert, C, Atkinson, E, Chan, L, De Andrade, M, Balschun, T, Mason, A, Myers, R, Zhang, J, Milkiewicz, P, Qu, J, Odin, J, Luketic, V, Bacon, B, Bodenheimer, H, Liakina, V, Vincent, C, Levy, C, Gregersen, P, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, P, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, M, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, L, Crosignani, A, Donato, M, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Mousa Hani, S, Muratori, L, Muratori, P, Niro, G, Palmieri, V, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Spreafico, M, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M, Zuin, M, Ch'Ng, C, Rahman, M, Yapp, T, Sturgess, R, Healey, C, Czajkowski, M, Gunasekera, A, Gyawali, P, Premchand, P, Kapur, K, Marley, R, Foster, G, Watson, A, Dias, A, Subhani, J, Harvey, R, Mccorry, R, Ramanaden, D, Gasem, J, Evans, R, Mathialahan, T, Shorrock, C, Lipscomb, G, Southern, P, Tibble, J, Gorard, D, Palegwala, A, Jones, S, Carbone, M, 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, Stephen, 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, Singhal, A, Gee, I, Ang, Y, Ransford, R, Gotto, J, Millson, C, Bowles, J, Thomas, C, Harrison, M, Galaska, R, Kendall, J, Whiteman, J, Lawlor, C, Gray, C, Elliott, K, Mulvaney Jones, C, Hobson, L, Van Duyvenvoorde, G, Loftus, A, Seward, K, Penn, R, Maiden, J, Damant, R, Hails, J, Cloudsdale, R, Silvestre, V, Glenn, S, Dungca, E, Wheatley, N, Doyle, H, Kent, M, Hamilton, C, Braim, D, Wooldridge, H, Abrahams, R, Paton, A, Lancaster, N, Gibbins, A, Hogben, K, Desousa, P, Muscariu, F, Musselwhite, J, Mckay, A, Tan, L, Foale, C, Brighton, J, Flahive, K, Nambela, E, Townshend, P, Ford, C, Holder, S, Palmer, C, Featherstone, J, Nasseri, M, Sadeghian, J, Williams, B, Rolls, S, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, Durant, E, Bishop, R, Ncube, N, Tripoli, S, Casey, R, Cowley, C, Miller, R, Houghton, K, Ducker, S, Wright, F, Bird, B, Baxter, G, Keggans, J, Hughes, M, Grieve, E, Young, K, Williams, D, Ocker, K, Hines, F, Martin, K, Innes, C, Valliani, T, Fairlamb, H, Thornthwaite, S, Eastick, A, Tanqueray, E, Morrison, J, Holbrook, B, Browning, J, Walker, K, Congreave, S, Verheyden, J, Slininger, S, Stafford, L, O'Donnell, D, Ainsworth, M, Lord, S, Kent, L, March, L, Dickson, C, Simpson, D, Longhurst, B, Hayes, M, Shpuza, E, White, N, Besley, S, Pearson, S, Wright, A, Jones, L, Gunter, E, Dewhurst, H, Fouracres, A, Farrington, L, Graves, L, Marriott, S, Leoni, M, Tyrer, D, Dali Kemmery, L, Lambourne, V, Green, M, Sirdefield, D, Amor, K, Colley, J, Shinder, B, Jones, J, Mills, M, Carnahan, M, Taylor, N, Boulton, K, Tregonning, J, Brown, C, Clifford, G, Archer, E, Hamilton, M, Curtis, J, Shewan, T, Walsh, S, Warner, K, Netherton, K, Mupudzi, M, Gunson, B, Gitahi, J, Gocher, D, Batham, S, Pateman, H, Desmennu, S, Conder, J, Clement, D, Gallagher, S, Orpe, J, Chan, P, Currie, L, O'Donohoe, L, Oblak, M, Morgan, L, Quinn, M, Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, and Kordula, J
- Subjects
Liver Cirrhosis ,Genetics and Molecular Biology (all) ,pathogenesi ,risk assessment EMTREE medical terms: Article ,genetic association ,genotype ,EMTREE drug terms: chemokine receptor CCR6 ,genetic risk ,Biochemistry ,meta-analysi ,primary biliary cirrhosi ,chemokine receptor CCR6 [EMTREE drug terms] ,single nucleotide polymorphism ,genetic variability ,Article [risk assessment EMTREE medical terms] ,Liver Cirrhosis, Biliary ,pathogenesis ,Biliary ,Chemistry (all) ,STAT protein GEOBASE Subject Index: disease treatment ,cohort analysis ,genome wide meta analysis PBC ,signal transduction ,gene locus ,cohort analysi ,CBP ,Article ,Physics and Astronomy (all) ,macrophage inflammatory protein 3alpha ,Humans ,controlled study ,human ,interleukin 27 ,genome ,Biochemistry, Genetics and Molecular Biology (all) ,meta analysi ,interleukin 12p40 ,interleukin 12 ,Janus kinase ,meta-analysis ,pathogen ,genetic predisposition ,major clinical study ,meta analysis ,primary biliary cirrhosis ,disease treatment [STAT protein GEOBASE Subject Index] ,Genome-Wide Association Study ,gene locu - Abstract
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined, Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.
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- 2015
30. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis
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Gideon M. Hirschfield, Maryam Ebadi, Xavier Verhelst, Federica Malinverno, Nora Cazzagon, Pierre Belnou, Christophe Corpechot, Falk Rauchfuss, Olivier Boillot, Raoul Poupon, Jérôme Dumortier, Palak J. Trivedi, Maria Francesca Donato, Sascha Chopra, Dennis Eurich, Francesco Paolo Russo, Martina Sterneck, Aldo J. Montano-Loza, Maren H. Harms, Fabrice Carrat, Philipp A. Reuken, Christoph Schramm, Alexie Bosch, Albert Parés, Patrick McDowell, Davide Roccarina, Andrew Mason, Jorn C Goet, Bettina E. Hansen, Emiliano Giostra, Anna Reig, Annarosa Floreani, Dietmar Jacob, Douglas Thorburn, Olivier Chazouillères, Tony Bruns, Alessio Gerussi, Henk R. van Buuren, Filomena Conti, Frederik Nevens, Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Gastroenterology & Hepatology, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Graft Rejection ,Male ,0301 basic medicine ,Cholagogues and Choleretics ,Cirrhosis ,Survival ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Placebo-controlled study ,Liver transplantation ,PBC ,Gastroenterology ,UDCA ,0302 clinical medicine ,MED/12 - GASTROENTEROLOGIA ,Recurrence ,Liver Cirrhosis, Biliary ,Ursodeoxycholic Acid ,Hazard ratio ,Middle Aged ,Ursodeoxycholic acid ,3. Good health ,Survival Rate ,Treatment Outcome ,Tacrolimu ,Cyclosporine ,Tacrolimus ,Transplantation ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Immunosuppressive Agents ,medicine.drug ,Risk ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Hepatology ,business.industry ,Retrospective cohort study ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Regimen ,030104 developmental biology ,MED/09 - MEDICINA INTERNA ,business ,Follow-Up Studies - Abstract
Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p
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- 2020
31. Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach
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Cristina Rigamonti, Rosanna Venere, Carla De Benedittis, Guido Carpino, Pietro Invernizzi, Italian Pbc Registry, Elisabetta Degasperi, Giacomo Mulinacci, Marco Carbone, Sarah Elisabeth O’Donnell, Diletta Overi, Sara Labanca, Vito Di Marco, A. Ciaccio, Vincenzo Cardinale, Mauro Viganò, Andrea Palermo, Annarosa Floreani, Daphne D’Amato, Nora Cazzagon, Vincenzo Ronca, Donatella Barisani, Laura Cristoferi, Federica Malinverno, Marco Marzioni, Domenico Alvaro, Clara Mancuso, Vincenza Calvaruso, Anna Fichera, Martina Lucà, Federica Cerini, Alessandra Nardi, Eugenio Gaudio, Antonino Picciotto, Nicola Zucchini, Monica Leutner, Alessio Gerussi, Laura Cristoferi, Vincenza Calvaruso, Diletta Overi 5 , Mauro Viganò 6 , Cristina Rigamonti 7 , Elisabetta Degasperi 8 , Vincenzo Cardinale 9 , Sara Labanca 10 , Nicola Zucchini 11 , Anna Fichera, Vito Di Marco, Monica Leutner 12 , Rosanna Venere 13 , Antonino Picciotto 10 , Martina Lucà 1 2 , Giacomo Mulinacci 1 2 , Andrea Palermo 1 2 , Alessio Gerussi 1 2 , Daphne D'Amato 1 2 , Sarah Elisabeth O'Donnell 1 2 , Federica Cerini 6 , Carla De Benedittis 7 , Federica Malinverno 1 2 , Vincenzo Ronca 1 2 , Clara Mancuso 1 2 , Nora Cazzagon 14 , Antonio Ciaccio 1 2 , Donatella Barisani 1 , Marco Marzioni 15 , Annarosa Floreani 16 17 , Domenico Alvaro 9 , Eugenio Gaudio 5 , Pietro Invernizzi 1 2 , Guido Carpino # 18 , Alessandra Nardi # 19 , Marco Carbone, Cristoferi, L, Calvaruso, V, Overi, D, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Fichera, A, Di Marco, V, Leutner, M, Venere, R, Picciotto, A, Lucà, M, Mulinacci, G, Palermo, A, Gerussi, A, D'Amato, D, O'Donnell, S, Cerini, F, De Benedittis, C, Malinverno, F, Ronca, V, Mancuso, C, Cazzagon, N, Ciaccio, A, Barisani, D, Marzioni, M, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, Nardi, A, and Carbone, M
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area under curve ,0301 basic medicine ,medicine.medical_specialty ,liver cirrhosis ,Diagnostic accuracy ,risk stratification ,PBC ,Gastroenterology ,primary biliary cholangiti ,elasticity imaging techniques ,female ,humans ,biliary ,male ,middle aged ,ROC curve ,sensitivity and specificity ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Internal medicine ,medicine ,Hepatology ,Receiver operating characteristic ,medicine.diagnostic_test ,Liver Cirrhosis, Biliary ,business.industry ,Original Articles ,medicine.disease ,transient elastography ,Autoimmune, Cholestatic and Biliary Disease ,030104 developmental biology ,Liver biopsy ,Cohort ,Original Article ,030211 gastroenterology & hepatology ,diagnostic accuracy ,Cut-off ,Transient elastography ,business ,fibrosi - Abstract
Background & aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Non-invasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis at disease presentation in PBC. Approach & results We collected data from 167 consecutive treatment-naive PBC patients who underwent liver biopsy(LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves(AUROCs) for advanced fibrosis (Ludwig stage≥III). The effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. Derivation cohort consisted of 126 patients with valid LSM and LB, VCTE identified patients with advanced fibrosis with AUROC of 0.89. LSM cut-offs ≤6.5kPa and >11.0kPa enabled to exclude and confirm, respectively, advanced fibrosis (negative predictive value[NPV]=0.94, positive predictive value[PPV]=0.89, error rate=5.6%). These values were externally validated in an independent cohort of 91 PBC patients(NPV=0.93, PPV=0.89, error rate=8.6%). Multivariable analysis found the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions In a multicenter study of treatment-naive PBC patients, we identified two cut-offs (LSM≤6.5kPa and>11.0kPa) able to discriminate at diagnosis the presence or the absence, respectively, of advanced fibrosis in PBC patients, with external validation. In patients with LSM between these two cut-offs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.
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- 2021
32. Primary Sclerosing Cholangitis: Burden of Disease and Mortality Using Data from the National Rare Diseases Registry in Italy
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Giada Minelli, Laura Cristoferi, Marco Carbone, Pietro Invernizzi, Annarosa Floreani, Alessio Gerussi, Valerio Manno, Yllka Kodra, Federica Malinverno, Adele Rocchetti, Vincenzo Ronca, Domenica Taruscio, Susanna Conti, Carbone, M, Kodra, Y, Rocchetti, A, Manno, V, Minelli, G, Gerussi, A, Ronca, V, Malinverno, F, Cristoferi, L, Floreani, A, Invernizzi, P, Conti, S, and Taruscio, D
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Male ,Pediatrics ,Delayed Diagnosis ,endocrine system diseases ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Disease ,registry ,State Medicine ,0302 clinical medicine ,Cost of Illness ,Epidemiology ,Registries ,030212 general & internal medicine ,Child ,Cause of death ,education.field_of_study ,Incidence (epidemiology) ,digestive, oral, and skin physiology ,autoimmune liver disease ,rare diseases ,primary sclerosing cholangitis ,Middle Aged ,Primary sclerosing cholangiti ,Italy ,Child, Preschool ,Cohort ,Female ,030211 gastroenterology & hepatology ,epidemiology ,Adult ,medicine.medical_specialty ,cholestatic liver disease ,Adolescent ,Cholangitis, Sclerosing ,Population ,digestive system ,Article ,Primary sclerosing cholangitis ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,Gallbladder cancer ,education ,Aged ,Retrospective Studies ,business.industry ,lcsh:R ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,Infant ,medicine.disease ,digestive system diseases ,business ,Rare disease - Abstract
Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers, and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence, survival and cause of mortality of PSC in Italy, using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male, mean age at disease onset and at diagnosis were 33 and 37 years, respectively, highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related, 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC, population-based cohort&rsquo, s studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary, single-centre series. Moreover, the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service
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- 2020
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33. Additive beneficial effects of Fibrates combined with Obeticholic acid in the treatment of patients with Primary Biliary Cholangitis and inadequate response to second-line therapy: data from the Italian PBC Study Group
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G. Marconi, Clara Mancuso, Chiara Milani, Nora Cazzagon, A. Floreani, Laura Cristoferi, Alessio Gerussi, Marco Marzioni, S. E. O'Donnell, Federica Malinverno, Marco Carbone, Pietro Invernizzi, Daphne D’Amato, D'Amato, D, O'Donnell, S, Cazzagon, N, Marconi, G, Gerussi, A, Cristoferi, L, Malinverno, F, Mancuso, C, Milani, C, Marzioni, M, Floreani, A, Invernizzi, P, and Carbone, M
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medicine.medical_specialty ,Second-line therapy ,Hepatology ,business.industry ,Obeticholic Acid ,Gastroenterology ,Obeticholic acid ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Medicine ,Primary Biliary Cholangiti ,Fibrate ,New Therapy ,business ,Beneficial effects - Published
- 2020
34. Comprehensive review of autoantibodies in patients with hyper-IgM syndrome
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Zakera Shums, Mehdi Trifa, Imen Ben-Mustapha, Qubo Chen, Christopher Chang, Marco Carbone, Gary L. Norman, Francesca Bernuzzi, Mohamed-Ridha Barbouche, Federica Malinverno, M. Eric Gershwin, Nourhen Agrebi, Haiyan Zhang, Pietro Invernizzi, Barbouche, M, Chen, Q, Carbone, M, Ben-Mustapha, I, Shums, Z, Trifa, M, Malinverno, F, Bernuzzi, F, Zhang, H, Agrebi, N, Norman, G, Chang, C, Gershwin, M, and Invernizzi, P
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Male ,0301 basic medicine ,Hyper IgM syndrome ,Immunology ,Infectious Disease ,Hyper-IgM Immunodeficiency Syndrome ,Immunofluorescence ,primary biliary cholangiti ,Article ,hyper-immunoglobulin M syndrome ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,immunoglobulin M ,medicine ,Humans ,Immunology and Allergy ,Child ,Immunodeficiency ,Autoantibodies ,biology ,medicine.diagnostic_test ,business.industry ,Autoantibody ,Infant ,autoantibodie ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Liver ,Immunoglobulin M ,Case-Control Studies ,Child, Preschool ,030220 oncology & carcinogenesis ,biology.protein ,Primary immunodeficiency ,Female ,Antibody ,business ,immunodeficiency ,Hyperimmunoglobulin M Syndrome - Abstract
Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene. The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis. In the present study, we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome. Serum, liver-related and liver-not-related autoantibodies IgG, IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients (8 males and 5 females, aged 1–12 years) with hyper-immunoglobulin M syndrome during 1995–2012 and, as controls, 21 age- and gender-matched blood donors. The level of IgM antibody against MIT3 was significantly higher in patients than in controls (35.8 vs 10.7, P=0.002). Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls (P
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- 2018
35. From pathogenesis to novel therapies in the treatment of primary biliary cholangitis
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Hani S Mousa, M. Eric Gershwin, Vincenzo Ronca, Pietro Invernizzi, Federica Malinverno, Francesca Bernuzzi, Marco Carbone, Ronca, V, Carbone, M, Bernuzzi, F, Malinverno, F, Mousa, H, Gershwin, M, and Invernizzi, P
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0301 basic medicine ,medicine.medical_specialty ,Cholangitis ,Immunology ,TGR-5 agonist ,Intrahepatic bile ducts ,Autoimmunity ,FGF-19 ,Chenodeoxycholic Acid ,Gastroenterology ,Pathogenesis ,03 medical and health sciences ,Liver disease ,chemistry.chemical_compound ,0302 clinical medicine ,Ductopenia ,Cholestasis ,MED/12 - GASTROENTEROLOGIA ,Fibrosis ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Molecular Targeted Therapy ,ASBT antagonist ,OCA ,fibrate ,Liver Cirrhosis, Biliary ,business.industry ,autoimmune liver disease ,Ursodeoxycholic Acid ,Obeticholic acid ,novel therapie ,medicine.disease ,Ursodeoxycholic acid ,Bile Ducts, Intrahepatic ,030104 developmental biology ,Liver ,chemistry ,Primary biliary cholangiti ,Ustekinumab ,030211 gastroenterology & hepatology ,Immunotherapy ,business ,medicine.drug - Abstract
Introduction: Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis and fibrosis, and leading to liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapy for the treatment of PBC patients. This is effective in majority of patients; however, up to 20 percent of patients have an incomplete response to UDCA therapy and have a reduced prognosis as compared to healthy individuals. Obeticholic acid (OCA) has been recently registered as second-line therapy for patients with incomplete response to UDCA, with plans to demonstrate the long-term clinical efficacy. Areas covered: Recent evolution in our understanding of disease mechanisms is leading to the advent of new and re-purposed therapeutic agents targeting key processes in the etiopathogenesis. Several therapeutic targets have been proposed which can be categorized into three compartments: immune, biliary and fibrosis. In this review we describe the main biological mechanisms underpinning disease development and progression in PBC and the new targeted therapies on the horizon. Expert commentary: Testing new drugs towards hard clinical endpoints is challenging in PBC due to its low prevalence and the slow progression of the disease. Novel promising biomarkers are under study and should be evaluated as surrogate endpoints in clinical trials.
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- 2017
36. Accuracy of liver stiffness measurement in assessing liver fibrosis in naive patients with primary biliary cholangitis
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LAURA CRISTOFERI, Nardi, Alessandra, Vigano, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Cazzagon, Nora, Luca, Martina, Overi, Diletta, Gerussi, Alessio, D Amato, Daphne, O Donnell, Sarah Elisabeth, Cerini, Federica, Benedittis, Carla, Cadamuro, Massimiliano, Malinverno, Federica, Floreani, Annarosa, Alvaro, Domenico, Gaudio, Eugenio, Invernizzi, Pietro, Carpino, Guido, Carbone, Marco, Cristoferi, L, Nardi, A, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Leutner, M, Venere, R, Picciotto, A, Cazzagon, N, Lucà, M, Overi, D, Gerussi, A, D’Amato, D, O’Donnell, S, Cerini, F, De Benedittis, C, Cadamuro, M, Malinverno, F, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, and Carbone, M
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Hepatology ,Primary biliary cholangiti ,Fibrosi ,Autoimmune liver disease ,Vibration-Controlled Transient Elastography ,Risk stratification - Abstract
Background and Aims: Non-invasive evaluation of liver fibrosis in primary biliary cholangitis (PBC) with Liver Stiffness Measurements (LSM) by Transient Elastography (TE) is routinely undertaken at diagnosis for disease staging and risk stratification. However, evidence on correlation between LSM and liver fibrosis is based on cross-sectional studies in PBC-treated patients. Moreover, the impact of potential confounders, e.g. cholestasis and steatosis, is unclear. Aim of our study was to investigate the accuracy of LSM to predict moderate to severe fibrosis in newly diagnosed PBC patients naïve to therapy. Method: We collected data from 182 adult patients who underwent liver biopsy (LB) for PBC at diagnosis in five Italian liver centers from Jan 2006 through Aug 2019. TE examinations within 3 months from LB were included. LB were scored centrally by two expert pathologists, blinded to clinical data and disease stage, according to Ludwig staging system. In all patients Fibrosis-4 (FIB-4) and aspartate aminotransferase [AST]/platelet ratio (APRI) score have been calculated. Diagnostic accuracy of LSM, FIB-4 and APRI score was estimated using the area under the receiver operating characteristic curves (AUROCs) for fibrosis. The effects of liver biochemistry and histological parameters were appraised using multivariable logistic model. Results: 123 PBC patients had adequate LB (≥9 portal tracts) and valid LSM values. According to histological assessment, Ludwig stage distribution was as follows: stage I = 38 (30.9%), stage II = 46(37.4%), stage III = 27 (21.9%), stage IV = 12 (9.8%). TE identified patients with Ludwig stage III/IV with an AUROC of 0.83 (95% confidence interval [CI] (0.74, 0.90)) (Fig.1). The optimal threshold was identified at 6.75kPa (CI (6.55, 7.50)), with 85% of sensitivity, 75% of specificity, 78% of accuracy and 6 false negative. TE was superior to APRI and FIB-4 having AUROC of 0.638 (CI = (0.535, 0.740)) and 0.641 (CI = (0.516, 0.766)), respectively. At multivariable analysis only LSM was associated with liver fibrosis and no significant effect of biochemical measures and steatosis was found. Conclusion: LSM is accurate to predict moderate to severe liver fibrosis at diagnosis in PBC naïve patients using a threshold of 6.75kPa with an AUROC of 0.83. TE outperformed FIB-4 and APRI score and is not confounded by liver biochemistry and steatosis. These data can inform strategies for patient surveillance and trial design in PBC.
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- 2020
37. FRI-008-Incidence, prevalence and mortality of primary sclerosing cholangitis in Italy: A population-based study
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Giada Minelli, Vincenzo Ronca, Alessio Gerussi, Yllka Kodra, Federica Malinverno, Pietro Invernizzi, Annarosa Floreani, Adele Rocchetti, Susanna Conti, Valerio Manno, Marco Carbone, Domenica Taruscio, Laura Cristoferi, Carbone, M, Kodra, Y, Rocchetti, A, Manno, V, Minelli, G, Gerussi, A, Ronca, V, Malinverno, F, Cristoferi, L, Floreani, A, Invernizzi, P, Conti, S, and Taruscio, D
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Population based study ,Pediatrics ,medicine.medical_specialty ,Hepatology ,business.industry ,Epidemiology ,primary sclerosing cholangiti ,Medicine ,epidemiology ,business ,medicine.disease ,Primary sclerosing cholangitis ,Incidence prevalence - Published
- 2019
38. THU-010-Shedding light on the X chromosome contribution to the genetic architecture of primary biliary cholangitis
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Elvezia Maria Paraboschi, Federica Malinverno, Alessio Gerussi, Laura Cristoferi, Pietro Invernizzi, Marco Carbone, Stefano Duga, Vincenzo Ronca, Gerussi, A, Paraboschi, E, Carbone, M, Ronca, V, Cristoferi, L, Malinverno, F, Duga, S, and Invernizzi, P
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Genetics ,X chromosome ,Hepatology ,genetics ,Biology ,Genetic architecture ,primary biliary cholangiti - Published
- 2019
39. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
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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)
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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 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p
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- 2018
40. A worldwide cross-ethnic study of quality of life in patients with PBC: Attitude or latitude?
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George F. Mells, Alessandra Frigerio, Federica Malinverno, L. Jopson, Anna Reig, Minami Yagi, Marco Carbone, Lorenzo Montali, D.E.J. Jones, Atsushi Tanaka, S. Pilar, Massimo Miglioretti, Pietro Invernizzi, Albert Parés, Francesca Bernuzzi, Andrea Gragnano, Carbone, M, Montali, L, Gragnano, A, Miglioretti, M, Frigerio, A, Yagi, M, Malinverno, F, Bernuzzi, F, Jopson, L, Reig, A, Pilar, S, Pares, A, Tanaka, A, Mells, G, Jones, D, and Invernizzi, P
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Quality of life (healthcare) ,Hepatology ,business.industry ,Gastroenterology ,Ethnic group ,Medicine ,In patient ,quality of life, Primary biliary cholangitis ,business ,Demography ,Latitude - Published
- 2018
41. Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis
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M. Mangano, Raffaella Viganò, Ilaria Lenci, Fabio Conti, M. Rendina, L. Pasulo, Laura Loiacono, Federica Malinverno, P. Burra, Paolo Pianta, Francesco Paolo Russo, Rosa Maria Iemmolo, Pietro Andreone, Pierluigi Toniutto, Antonietta Romano, Stefano Fagiuoli, Luca S. Belli, Francesco Giuseppe Foschi, Maria Francesca Donato, Paola Carrai, Mariarosa Tamè, Antonio Picciotto, S. Monico, A. M. Degli Antoni, Sonia Berardi, M.C. Morelli, Ranka Vukotic, Giuseppe Mazzella, Manuela Merli, M. Colpani, Vukotic, R, Conti, F, Fagiuoli, S, Morelli, M, Pasulo, L, Colpani, M, Foschi, F, Berardi, S, Pianta, P, Mangano, M, Donato, M, Malinverno, F, Monico, S, Tame, M, Mazzella, G, Belli, L, Vigano, R, Carrai, P, Burra, P, Russo, F, Lenci, I, Toniutto, P, Merli, M, Loiacono, L, Iemmolo, R, Degli Antoni, A, Romano, A, Picciotto, A, Rendina, M, Andreone, P, Morelli, M C, Foschi, F G, Donato, M F, Tamè, M, Belli, L S, Viganò, R, Russo, F P, and Degli Antoni, A M
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Liver Cirrhosis ,Male ,Simeprevir ,Time Factors ,Sofosbuvir ,Hepacivirus ,Kaplan-Meier Estimate ,medicine.disease_cause ,Severity of Illness Index ,Gastroenterology ,Hepatitis ,chemistry.chemical_compound ,0302 clinical medicine ,Liver Function Tests ,fibrosing cholestatic hepatiti ,Recurrence ,antiviral therapy ,Viral ,fibrosing cholestatic hepatitis ,liver transplant ,long-term outcome ,severe hepatitis C virus recurrence ,Aged ,Antiviral Agents ,Drug Therapy, Combination ,Female ,Genotype ,Hepatitis C ,Humans ,Liver Transplantation ,Middle Aged ,RNA, Viral ,Treatment Outcome ,Viral Load ,Hepatology ,Infectious Diseases ,Virology ,030220 oncology & carcinogenesis ,Combination ,030211 gastroenterology & hepatology ,medicine.drug ,medicine.medical_specialty ,Daclatasvir ,Hepatitis C virus ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,medicine ,business.industry ,Ribavirin ,medicine.disease ,chemistry ,RNA ,Liver function ,business - Abstract
Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P
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- 2017
42. Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach
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Federica Malinverno, Vincenzo Ronca, Hani S Mousa, Marco Carbone, Pietro Invernizzi, M. Eric Gershwin, Mousa, H, Carbone, M, Malinverno, F, Ronca, V, Gershwin, M, and Invernizzi, P
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0301 basic medicine ,medicine.medical_specialty ,Cholagogues and Choleretics ,Biologic ,Cholangitis ,Biliary cirrhosis ,Immunology ,Receptors, Cytoplasmic and Nuclear ,Disease ,Gastroenterology ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Primary biliary cirrhosis ,Ductopenia ,Farnesoid X receptor ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Stage (cooking) ,Budesonide ,Bile duct ,business.industry ,Liver Cirrhosis, Biliary ,Ursodeoxycholic Acid ,medicine.disease ,Ursodeoxycholic acid ,030104 developmental biology ,medicine.anatomical_structure ,Primary biliary cholangiti ,Disease Progression ,030211 gastroenterology & hepatology ,Bile Ducts ,business ,medicine.drug - Abstract
Primary biliary cholangitis (PBC; previously "primary biliary cirrhosis") is a cholestatic, putatively autoimmune-mediated liver disease with a clear female preponderance affecting the intrahepatic small and medium-size bile ducts and resulting in bile duct destruction, ductopenia and portal fibrosis that progresses slowly to biliary cirrhosis. Despite suboptimal response in one third of patients treated with ursodeoxycholic acid (UDCA), this remains the only FDA-approved agent for this disease. In this review, we cover recent advances in research that have yielded numerous agents currently at different stages of the drug pipeline, some of which are expected to be approved in the near future. We also discuss accumulating evidence supporting the use of older agents (fibrates and glucocorticoids) as an adjunctive therapy to UDCA in non-responsive patients. We suggest that with the imminent expansion of the therapeutic armamentarium for PBC, a more comprehensive approach - ideally taking into account not only biochemical markers of disease stage - is needed to better select patients in whom these strategies might be most useful. Studies are also needed to compare the relative efficacy of different proposed second-line treatments not only against UDCA monotherapy.
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- 2016
43. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis
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Ross L. Coppel, Lina Tan, David H. Adams, M. Eric Gershwin, Qiqun Tan, Qianjin Lu, Yixin Tan, Bochen Zhu, Francesca Bernuzzi, Ana Lleo, Tingting Jiang, Pietro Invernizzi, Weici Zhang, Ming Zhao, Luca Valenti, Wei Liao, Federica Malinverno, Qian Liu, Lleo, A, Zhang, W, Zhao, M, Tan, Y, Bernuzzi, F, Zhu, B, Liu, Q, Tan, Q, Malinverno, F, Valenti, L, Jiang, T, Tan, L, Liao, W, Coppel, R, Invernizzi, P, Lu, Q, Adams, D, and Gershwin, M
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Genetics ,0303 health sciences ,CXCR3 ,Primary biliary cirrhosi ,Research ,Bisulfite sequencing ,Promoter ,Methylation ,Biology ,X chromosome ,03 medical and health sciences ,0302 clinical medicine ,CpG site ,Genetic ,Primary biliary cirrhosis ,DNA methylation ,030211 gastroenterology & hepatology ,Epigenetics ,Molecular Biology ,CD8 ,Genetics (clinical) ,030304 developmental biology ,Developmental Biology - Abstract
Background Although the etiology of primary biliary cirrhosis (PBC) remains enigmatic, there are several pieces of data supporting the thesis that a strong genetic predisposition and environmental factors interact to produce a selective loss of tolerance. The striking female predominance of PBC has suggested that this sex predisposition may be secondary to epigenetic alterations on the X chromosome. In the present study, we rigorously defined the X chromosome methylation profile of CD4, CD8, and CD14 cells from 30 PBC patients and 30 controls. Genomic DNA from sorted CD4, CD8, and CD14 subpopulations was isolated, sonicated, and immunoprecipitated for analysis of methylation. All products were hybridized to a custom-tiled four-plex array containing 27,728 CpG islands annotated by UCSC and 22,532 well-characterized RefSeq promoter regions. Furthermore, bisulfite sequencing was then used for validation on a subsequent group of independent samples from PBC patients and controls. Thence, expression levels of selected X-linked genes were evaluated by quantitative real-time PCR with cDNA samples from all subjects. Results We report herein that a total of 20, 15, and 19 distinct gene promoters reflected a significant difference in DNA methylation in CD4+ T, CD8+ T, and CD14+ cells in patients with PBC. Interestingly, there was hypermethylation of FUNDC2 in CD8+ T cells and a striking demethylation of CXCR3 in CD4+ T cells, which inversely correlated with CXCR3 expression levels in CD4+ T cells from early-stage PBC patients. Conclusions Our data provides a set of genes with epigenetic alteration likely to be indicators of autoimmunity and emphasizes the role of CXCR3 in the natural history of PBC. Electronic supplementary material The online version of this article (doi:10.1186/s13148-015-0098-9) contains supplementary material, which is available to authorized users.
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44. Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.
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De Vincentis A, D'Amato D, Cristoferi L, Gerussi A, Malinverno F, Lleo A, Colapietro F, Marra F, Galli A, Fiorini C, Coco B, Brunetto M, Niro GA, Cotugno R, Saitta C, Cozzolongo R, Losito F, Giannini EG, Labanca S, Marzioni M, Marconi G, Morgando A, Pellicano R, Vanni E, Cazzagon N, Floreani A, Chessa L, Morelli O, Muratori L, Pellicelli A, Pompili M, Ponziani F, Tortora A, Rosina F, Russello M, Cannavò M, Simone L, Storato S, Viganò M, Abenavoli L, D'Antò M, De Gasperi E, Distefano M, Scifo G, Zolfino T, Calvaruso V, Cuccorese G, Palitti VP, Sacco R, Bertino G, Frazzetto E, Alvaro D, Mulinacci G, Palermo A, Scaravaglio M, Terracciani F, Galati G, Ronca V, Zuin M, Claar E, Izzi A, Picardi A, Invernizzi P, Vespasiani-Gentilucci U, and Carbone M
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- Albumins therapeutic use, Ascites drug therapy, Ascites etiology, Bilirubin, Chenodeoxycholic Acid analogs & derivatives, Humans, Liver Cirrhosis complications, Liver Cirrhosis drug therapy, Male, Liver Cirrhosis, Biliary complications, Liver Cirrhosis, Biliary drug therapy
- Abstract
Background & Aims: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy., Methods: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs)., Results: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA., Conclusions: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)
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- 2022
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45. Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach.
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Cristoferi L, Calvaruso V, Overi D, Viganò M, Rigamonti C, Degasperi E, Cardinale V, Labanca S, Zucchini N, Fichera A, Di Marco V, Leutner M, Venere R, Picciotto A, Lucà M, Mulinacci G, Palermo A, Gerussi A, D'Amato D, Elisabeth O'Donnell S, Cerini F, De Benedittis C, Malinverno F, Ronca V, Mancuso C, Cazzagon N, Ciaccio A, Barisani D, Marzioni M, Floreani A, Alvaro D, Gaudio E, Invernizzi P, Carpino G, Nardi A, and Carbone M
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- Area Under Curve, Elasticity Imaging Techniques, Female, Humans, Liver Cirrhosis pathology, Liver Cirrhosis, Biliary pathology, Male, Middle Aged, ROC Curve, Sensitivity and Specificity, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis, Biliary diagnostic imaging
- Abstract
Background and Aims: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC., Approach and Results: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry., Conclusions: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
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- 2021
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46. Real-world experience with obeticholic acid in patients with primary biliary cholangitis.
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D'Amato D, De Vincentis A, Malinverno F, Viganò M, Alvaro D, Pompili M, Picciotto A, Palitti VP, Russello M, Storato S, Pigozzi MG, Calvaruso V, De Gasperi E, Lleo A, Castellaneta A, Pellicelli A, Cazzagon N, Floreani A, Muratori L, Fagiuoli S, Niro GA, Feletti V, Cozzolongo R, Terreni N, Marzioni M, Pellicano R, Pozzoni P, Baiocchi L, Chessa L, Rosina F, Bertino G, Vinci M, Morgando A, Vanni E, Scifo G, Sacco R, D'Antò M, Bellia V, Boldizzoni R, Casella S, Omazzi B, Poggi G, Cristoferi L, Gerussi A, Ronca V, Venere R, Ponziani F, Cannavò M, Mussetto A, Fontana R, Losito F, Frazzetto E, Distefano M, Colapietro F, Labanca S, Marconi G, Grassi G, Galati G, O'Donnell SE, Mancuso C, Mulinacci G, Palermo A, Claar E, Izzi A, Picardi A, Invernizzi P, Carbone M, and Vespasiani-Gentilucci U
- Abstract
Background & Aims: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions., Methods: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria ; the secondary endpoint was the biochemical response according to normal range criteria , defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed., Results: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria , and 11% by normal range criteria . Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%)., Conclusions: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC., Lay Summary: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Competing Interests: The authors have no conflicts of interest to declare related to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Author(s).)
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- 2021
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47. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis.
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Corpechot C, Chazouillères O, Belnou P, Montano-Loza AJ, Mason A, Ebadi M, Eurich D, Chopra S, Jacob D, Schramm C, Sterneck M, Bruns T, Reuken P, Rauchfuss F, Roccarina D, Thorburn D, Gerussi A, Trivedi P, Hirschfield G, McDowell P, Nevens F, Boillot O, Bosch A, Giostra E, Conti F, Poupon R, Parés A, Reig A, Donato MF, Malinverno F, Floreani A, Russo FP, Cazzagon N, Verhelst X, Goet J, Harms M, van Buuren H, Hansen B, Carrat F, and Dumortier J
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- Aged, Cyclosporine therapeutic use, Drug Therapy, Combination methods, Female, Follow-Up Studies, Humans, Immunosuppressive Agents therapeutic use, Liver Cirrhosis, Biliary mortality, Liver Cirrhosis, Biliary surgery, Male, Middle Aged, Recurrence, Retrospective Studies, Risk, Survival Rate, Treatment Outcome, Cholagogues and Choleretics administration & dosage, Graft Rejection mortality, Graft Rejection prevention & control, Liver Cirrhosis, Biliary etiology, Liver Cirrhosis, Biliary prevention & control, Liver Transplantation adverse effects, Ursodeoxycholic Acid administration & dosage
- Abstract
Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT., Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983-2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10-15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models., Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28-0.61; p <0.0001), graft loss (aHR 0.33; 95% CI 0.13-0.82; p <0.05), liver-related death (aHR 0.46; 95% CI 0.22-0.98; p <0.05), and all-cause death (aHR 0.69; 95% CI 0.49-0.96; p <0.05). On RMST analysis, preventive UDCA led to a survival gain of 2.26 years (95% CI 1.28-3.25) over a period of 20 years. Exposure to cyclosporine rather than tacrolimus had a complementary protective effect alongside preventive UDCA, reducing the cumulative incidence of PBC recurrence and all-cause death., Conclusions: Preventive UDCA after LT for PBC is associated with a reduced risk of disease recurrence, graft loss, and death. A regimen combining cyclosporine and preventive UDCA is associated with the lowest risk of PBC recurrence and mortality., Lay Summary: Recurrence of primary biliary cholangitis after liver transplantation is frequent and can impair graft and patient survival. We performed the largest international study of transplanted patients with primary biliary cholangitis to date. Preventive administration of ursodeoxycholic acid after liver transplantation was associated with reduced risk of disease recurrence, graft loss, liver-related and all-cause mortality. A regimen combining cyclosporine and preventive ursodeoxycholic acid was associated with the best outcomes., Competing Interests: Conflict of interest Dr. Corpechot reports receiving grants from Arrow and Intercept France, consulting fees from Intercept France, Inventiva Pharma and Genkyotex, and fees for teaching from Intercept France and GlaxoSmithKline France; Dr. Chazouillères, receiving grant support from Aptalis, fees for teaching from Mayoly Spindler, consulting fees from Genfit, and fees for teaching and consulting fees from Intercept; Dr. Schramm, receiving lecture fees from Falk Pharma; Dr. Reuken, receiving lecture fees from CSL Behring, consulting fees from Boston Scientific, and travel expenses from Merz Pharmaceuticals; Dr. Rauchfuss, receiving lecture fees from Chiesi, Novartis, Roche and Astellas; Dr. Verhelst, receiving travel grants from Falk Pharma; Dr. Bruns, receiving lecture fees from AbbVie, Norgine, Intercept Pharmaceuticals, and Falk Pharma, and consulting fees from Intercept Pharmaceuticals; Dr. Cazzagon receiving consulting fees from Intercept Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2020
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48. Primary Sclerosing Cholangitis: Burden of Disease and Mortality Using Data from the National Rare Diseases Registry in Italy.
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Carbone M, Kodra Y, Rocchetti A, Manno V, Minelli G, Gerussi A, Ronca V, Malinverno F, Cristoferi L, Floreani A, Invernizzi P, Conti S, and Taruscio D
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- Adolescent, Adult, Aged, Child, Child, Preschool, Cost of Illness, Delayed Diagnosis, Female, Humans, Infant, Infant, Newborn, Italy epidemiology, Male, Middle Aged, Rare Diseases epidemiology, Rare Diseases mortality, Registries, Retrospective Studies, State Medicine, Young Adult, Cholangitis, Sclerosing epidemiology, Cholangitis, Sclerosing mortality
- Abstract
Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias . The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort's studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service.
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- 2020
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49. Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival.
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Montano-Loza AJ, Hansen BE, Corpechot C, Roccarina D, Thorburn D, Trivedi P, Hirschfield G, McDowell P, Poupon R, Dumortier J, Bosch A, Giostria E, Conti F, Parés A, Reig A, Floreani A, Russo FP, Goet JC, Harms MH, van Buuren H, Van den Ende N, Nevens F, Verhelst X, Donato MF, Malinverno F, Ebadi M, and Mason AL
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- Age of Onset, Biomarkers blood, Biopsy, Europe, Female, Humans, Immunosuppressive Agents adverse effects, Liver Cirrhosis, Biliary blood, Liver Cirrhosis, Biliary diagnosis, Liver Cirrhosis, Biliary mortality, Liver Transplantation mortality, Male, Middle Aged, North America, Recurrence, Risk Factors, Tacrolimus adverse effects, Time Factors, Treatment Outcome, Graft Survival, Liver Cirrhosis, Biliary surgery, Liver Transplantation adverse effects
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Background & Aims: Primary biliary cholangitis (PBC) frequently recurs after liver transplantation. We evaluated risk factors associated with recurrence of PBC and its effects on patient and graft survival in a multicenter, international cohort (the Global PBC Study Group)., Methods: We collected demographic and clinical data from 785 patients (89% female) with PBC who underwent liver transplantation (mean age, 54 ± 9 years) from February 1983 through June 2016, among 13 centers in North America and Europe. Results from biochemical tests performed within 12 months of liver transplantation were analyzed to determine whether markers of cholestasis could identify patients with recurrence of PBC (based on histologic analysis). Patients were followed for a median 6.9 years (interquartile range, 6.1-7.9 years)., Results: PBC recurred in 22% of patients after 5 years and 36% after 10 years. Age at diagnosis <50 years (hazard ratio [HR], 1.79; 95% CI, 1.36-2.36; P < .001), age at liver transplantation <60 years (HR, 1.39; 95% CI, 1.02-1.90; P = .04), use of tacrolimus (HR, 2.31; 95% CI, 1.72-3.10; P < .001), and biochemical markers of severe cholestasis (bilirubin ≥100 μmol or alkaline phosphatase >3-fold the upper limit of normal) at 6 months after liver transplantation (HR, 1.79; 95% CI, 1.16-2.76; P = .008) were associated with higher risk of PBC recurrence, whereas use of cyclosporine reduced risk of PBC recurrence (HR, 0.62; 95% CI, 0.46-0.82; P = .001). In multivariable Cox regression with time-dependent covariate, recurrence of PBC significantly associated with graft loss (HR, 2.01; 95% CI, 1.16-3.51; P = .01) and death (HR, 1.72; 95% CI, 1.11-2.65; P = .02)., Conclusions: Younger age at the time of diagnosis with PBC or at liver transplantation, tacrolimus use, and biochemical markers of cholestasis after liver transplantation are associated with PBC recurrence. PBC recurrence reduces odds of graft and patient survival. Strategies are needed to prevent PBC recurrence or reduce its negative effects., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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50. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score.
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Carbone M, Nardi A, Flack S, Carpino G, Varvaropoulou N, Gavrila C, Spicer A, Badrock J, Bernuzzi F, Cardinale V, Ainsworth HF, Heneghan MA, Thorburn D, Bathgate A, Jones R, Neuberger JM, Battezzati PM, Zuin M, Taylor-Robinson S, Donato MF, 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 DD, Cordell HJ, Hirschfield GM, Alexander GJ, Sandford RN, Jones DE, Invernizzi P, and Mells GF
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- Age of Onset, Alkaline Phosphatase blood, Area Under Curve, Bilirubin blood, Female, Humans, Linear Models, Liver Cirrhosis, Biliary blood, Liver Cirrhosis, Biliary pathology, Male, Middle Aged, ROC Curve, Risk Factors, Time-to-Treatment, Transaminases blood, Treatment Outcome, Cholagogues and Choleretics therapeutic use, Decision Support Techniques, Liver Cirrhosis, Biliary drug therapy, Ursodeoxycholic Acid therapeutic use
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Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters., Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples., Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p<0·0001), higher total bilirubin concentration (p=0·0003), lower aminotransferase concentration (p=0·0012), younger age (p<0·0001), longer interval from diagnosis to the start of UDCA treatment (treatment time lag, p<0·0001), and worsening of alkaline phosphatase concentration from diagnosis (p<0·0001). Based on these variables, we derived a predictive score of UDCA response. In the external validation cohort, 460 patients diagnosed with primary biliary cholangitis were treated with UDCA, with follow-up data until May 31, 2016. In this validation cohort, the area under the receiver operating characteristic curve for the score was 0·83 (95% CI 0·79-0·87). In 20 liver biopsy samples from patients with primary biliary cholangitis, the UDCA response score was associated with ductular reaction (r=-0·556, p=0·0130) and intermediate hepatocytes (probability of response was 0·90 if intermediate hepatocytes were absent vs 0·51 if present)., Interpretation: We have derived and externally validated a model based on pretreatment variables that accurately predicts UDCA response. Association with histological features provides face validity. This model provides a basis to explore alternative approaches to treatment stratification in patients with primary biliary cholangitis., Funding: UK Medical Research Council and University of Milan-Bicocca., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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