111 results on '"Moisés Diago"'
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2. Global multi-stakeholder endorsement of the MAFLD definition
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Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. Peltekian, Xuebin Peng, Liang Peng, Ying Peng, Rahul Pengoria, Martina Perez, José Luis Pérez, Norma Marlene Pérez, Marcello Persico, Mário Guimarães Pessoa, Salvatore Petta, Mathew Philip, Maria Corina Plaz Torres, Naveen Polavarapu, Jaime Poniachik, Piero Portincasa, Chunwen Pu, Tuğrul Pürnak, Edhie Purwanto, Xiaolong Qi, Xingshun Qi, Zibing Qian, Zhao Qiang, Zengpei Qiao, Liang Qiao, Alberto Queiroz, Atoosa Rabiee, Manal Radwan, Alain Marcel Rahetilahy, Yasmin Ramadan, Dina Ramadan, Anis Safura Ramli, Grant A. Ramm, Ao Ran, Ivan Rankovic, Huiying RAO, Sara Raouf, Sayantan Ray, Nancy Reau, Ahmed Refaat, Thomas Reiberger, Jose M Remes-Troche, Eira Cerda Reyes, Ben Richardson, Ezequiel Ridruejo, Sergio Riestra Jimenez, Ibrahim Rizk, Stuart Roberts, Juan Pablo Roblero, Jorge Alberto Prado Robles, Don Rockey, Manuel Rodríguez, Heriberto Rodríguez Hernández, Eva Román, Fernando Gomes Romeiro, Stefano Romeo, Jose Miguel Rosales-Zabal, Georgina R. Roshdi, Natalia Rosso, Andres Ruf, Patricia Cordero Ruiz, Nelia R. Runes, Andrea Ruzzenente, Marno Ryan, Ahmed Saad, Eman BE Sabbagh, Meriam Sabbah, Shimaa Saber, Reham Sabrey, Ramy Sabry, Maysaa Abdallah Saeed, Dina Said, Ebada M Said, Mohammad Amin Sakr, Yara Salah, Rabab Maamoun Salama, Asmaa Salama, Hussein Saleh, Ahmed Saleh, Ahmed Salem, Ahmed Thabet Salem, Alkassoum Salifou, Aso Faeq Salih, Abdallah Salman, Hanen Samouda, Faisal Sanai, Juan Francisco Sánchez-Ávila, Lakshumanan Sanker, Tomoya Sano, Miquel Sanz, Tobokalova Saparbu, Rohit Sawhney, Fatma Sayed, Sayed A. Sayed, Ashraf Othman Sayed, Manar Sayed, Giada Sebastiani, Laura Secadas, Khawaja Qamaruddin Sediqi, Sameh Seif, Nady Semida, Ebubekir Şenateş, Elena Daniela Serban, Lawrence Serfaty, Wai-Kay Seto, Ikram Sghaier, Min Sha, Hamada M. Shabaan, Lobna Shalaby, Inass Shaltout, Ala I. Sharara, Vishal Sharma, Isaac Thom Shawa, Ahmed Shawkat, Nehal Shawky, Osama Shehata, Sinead Sheils, Abate Bane Shewaye, Guojun Shi, Junping Shi, Shigeo Shimose, Tomotake Shirono, Lan Shou, Ananta Shrestha, Guanghou Shui, William Sievert, Solveig Sigurdardottir, Mostafa Mohamed Sira, Riyadh Siradj, Cecilia Sison, Linda Smyth, Reham Soliman, Jose D Sollano, Roger Sombie, Mark Sonderup, Siddharth Sood, German Soriano, Catherine A M Stedman, Oksana Stefanyuk, Davor Štimac, Simone Strasser, Pavel Strnad, Katherine Stuart, Wen Su, Minghua Su, Yoshio Sumida, Shuji Sumie, Dan-Qin Sun, Jing Sun, Hiroyuki Suzuki, Gianluca Svegliati-Baroni, Mohamed Osman Swar, S. TAHARBOUCHT, Zenab Taher, Saori Takamura, Lin Tan, Soek-Siam Tan, Tawesak Tanwandee, Sara Tarek, Ghelimici Tatiana, Federica Tavaglione, Gina Y. Tecson, Hoi-Poh Tee, Rolf Teschke, Mostafa Tharwat, Vo Duy Thong, Mark Thursz, Tulari Tine, Claudio Tiribelli, Ieva Tolmane, Jing Tong, Marco Tongo, Mamdouh Torkie, Aldo Torre, Esther A Torres, Meri Trajkovska, Sombat Treeprasertsuk, Tsubasa Tsutsumi, Thomas Tu, Josep A. Tur, Dilara Turan, Svetlana Turcan, Svetlana Turkina, Engin Tutar, Christian Tzeuton, Rose Ugiagbe, Ahmet Uygun, Michele Vacca, Pietro Vajro, David Van der Poorten, Laurens A. Van Kleef, Eliza Vashakidze, Carlos Moctezuma Velazquez, Mirtha Infante Velazquez, Sandro Vento, Veronique Verhoeven, Umberto Vespasiani-Gentilucci, Shireene Ratna Vethakkan, Josep Vilaseca, Libor Vítek, Ance Volkanovska, Michael Wallace, Wang Wan, Yan Wang, Ying Wang, Xiaolin Wang, Xuemei Wang, Chengyan Wang, Chunjiong Wang, Mingjie Wang, Pelden Wangchuk, Martin Weltman, MaryFrances White, Johannes Wiegand, Mohamed-Naguib Wifi, Alan Wigg, Markus Wilhelmi, Remon William, Henning Wittenburg, Shengjie Wu, Abdu Mohammed Wubeneh, Hongping Xia, Jian Xiao, Xiao Xiao, Wang Xiaofeng, Wanyuan Xiong, Liang Xu, Jie Xu, Weiguo Xu, Jing-Hang Xu, Keshu Xu, Yumin Xu, Shi-Hao Xu, Meng Xu, Aimin Xu, Chengfu Xu, Hongmei Yan, Jingyi Yang, Rui-Xu Yang, Yating Yang, Qinhe Yang, Naibin Yang, Jia Yao, Justine Yara, Serkan Yaraş, Nimet Yılmaz, Ramy Younes, Huda younes, Sona Young, Farah Youssef, Yanyan Yu, Ming-Lung Yu, Jing Yuan, Zhang Yue, Man-Fung Yuen, Wang Yun, Nonka Yurukova, Serag Zakaria, Samy Zaky, Maia Zaldastanishvili, Rodrigo Zapata, Nazanin Zare, Enver Zerem, Nema Zeriban, Xu Zeshuai, Huijie Zhang, Xuemei Zhang, Yupei Zhang, Wen-Hua Zhang, Xuchen Zhang, Yon-ping Zhang, Yuexin Zhang, Zhan-qing Zhang, Jingmin Zhao, Rong-Rong Zhao, Hongwei Zhao, Chao Zheng, Yijie Zheng, Ruidan Zheng, Tian-Lei Zheng, Kenneth Zheng, Xi Qiao Zhou, Yongjian Zhou, Yu-Jie Zhou, Hong Zhou, Ling Zhou, Yongning Zhou, Long dong Zhu, Yong Fen Zhu, Yueyong Zhu, Pei-Wu Zhu, Ebtesam Ziada, David Ziring, Li Ziyi, Shanshan Zou, Zhengsheng Zou, Huaibin Zou, Roberto Zuart Ruiz, UCL - (SLuc) Service de gastro-entérologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, Mendez-Sanchez, N, Bugianesi, E, Gish, R, Lammert, F, Tilg, H, Nguyen, M, Sarin, S, Fabrellas, N, Zelber-Sagi, S, Fan, J, Shiha, G, Targher, G, Zheng, M, Chan, W, Vinker, S, Kawaguchi, T, Castera, L, Yilmaz, Y, Korenjak, M, Spearman, C, Ungan, M, Palmer, M, El-Shabrawi, M, Gruss, H, Dufour, J, Dhawan, A, Wedemeyer, H, George, J, Valenti, L, Fouad, Y, Romero-Gomez, M, Eslam, M, Abate, M, Abbas, B, Abbassy, A, Abd El Ghany, W, Abd Elkhalek, A, Abd ElMajeed, E, Abdalgaber, M, Abdallah, M, Abdallah, N, Abdelaleem, S, Abdelghani, Y, Abdelghany, W, Abdelhalim, S, Abdelhamid, W, Abdelhamid, N, Abdelkader, N, Abdelkreem, E, Abdelmohsen, A, Abdelrahman, A, Abd-elsalam, S, Abdeltawab, D, Abduh, A, Abdulhakam, N, Abdulla, M, Abedpoor, N, Abenavoli, L, Aberg, F, Ablack, O, Abo elftouh, M, Abo-Amer, Y, Aboubkr, A, Aboud, A, Abouelnaga, A, Aboufarrag, G, Aboutaleb, A, Abundis, L, Adali, G, Adames, E, Adams, L, Adda, D, Adel, N, Adel Sayed, M, Afaa, T, Afredj, N, Aghayeva, G, Aghemo, A, Aguilar-Salinas, C, Ahlenstiel, G, Ahmady, W, Ahmed, W, Ahmed, A, Ahmed, S, Ahmed, H, Ahmed, R, Aigner, E, Akarsu, M, Akroush, M, Akyuz, U, Al Mahtab, M, Al Qadiri, T, Al Rawahi, Y, AL rubaee, R, Al Saffar, M, Alam, S, Al-Ani, Z, Albillos, A, Alboraie, M, Al-Busafi, S, Al-Emam, M, Alharthi, J, Ali, K, Ali, B, Ali, M, Ali, R, Alisi, A, AL-Khafaji, A, Alkhatry, M, Aller, R, Almansoury, Y, Al-Naamani, K, Alnakeeb, A, Alonso, A, Alqahtani, S, Alrabadi, L, Alswat, K, Altaher, M, Altamimi, T, Altamirano, J, Alvares-da-Silva, M, Aly, E, Alzahaby, A, Alzamzamy, A, Amano, K, Amer, M, Amin, M, Amin, S, Amir, A, Ampuero, J, Anas, N, Andreone, P, Andriamandimby, S, Anees, M, Angela, P, Antonios, M, Arafat, W, Araya, J, Armendariz-Borunda, J, Armstrong, M, Ashktorab, H, Aspichueta, P, Assal, F, Atef, M, Attia, D, Atwa, H, Awad, R, Awad, M, Awny, S, Awolowo, O, Awuku, Y, Ayada, I, Aye, T, Ayman, S, Ayman, H, Ayoub, H, Azmy, H, Babaran, R, Badreldin, O, Badry, A, Bahcecioglu, I, Bahour, A, Bai, J, Balaban, Y, Balasubramanyam, M, Bamakhrama, K, Banales, J, Bangaru, B, Bao, J, Barahona, J, Barakat, S, Barbalho, S, Barbra, B, Barranco, B, Barrera, F, Baumann, U, Bazeed, S, Bech, E, Benayad, A, Benesic, A, Bernstein, D, Bessone, F, Birney, S, Bisseye, C, Blake, M, Bobat, B, Bonfrate, L, Bordin, D, Bosques-Padilla, F, Boursier, J, Boushab, B, Bowen, D, Bravo, P, Brennan, P, Bright, B, Broekaert, I, Buque, X, Burgos-Santamaria, D, Burman, J, Busetto, L, Byrne, C, Cabral-Prodigalidad, P, Cabrera-Alvarez, G, Cai, W, Cainelli, F, Caliskan, A, Canbay, A, Cano-Contreras, A, Cao, H, Cao, Z, Carrion, A, Carubbi, F, Casanovas, T, Castellanos Fernandez, M, Chai, J, Chan, S, Charatcharoenwitthaya, P, Chavez-Tapia, N, Chayama, K, Chen, J, Chen, L, Chen, Z, Chen, H, Chen, S, Chen, Q, Chen, Y, Chen, G, Chen, E, Chen, F, Chen, P, Cheng, R, Cheng, W, Chieh, J, Chokr, I, Cholongitas, E, Choudhury, A, Chowdhury, A, Chukwudike, E, Ciardullo, S, Clayton, M, Clement, K, Cloa, M, Coccia, C, Collazos, C, Colombo, M, Cosar, A, Cotrim, H, Couillerot, J, Coulibaly, A, Crespo, G, Crespo, J, Cruells, M, Cua, I, Dabbous, H, Dalekos, G, D'Alia, P, Dan, L, Dao, V, Darwish, M, Datz, C, Davalos-Moscol, M, Dawoud, H, de Careaga, B, de Knegt, R, de Ledinghen, V, de Silva, J, Debzi, N, Decraecker, M, Del Pozo, E, Delgado, T, Delgado-Blanco, M, Dembinski, L, Depina, A, Derbala, M, Desalegn, H, Desbois-Mouthon, C, Desoky, M, Dev, A, Di Ciaula, A, Diago, M, Diallo, I, Diaz, L, Dirchwolf, M, Dongiovanni, P, Dorofeyev, A, Dou, X, Douglas, M, Doulberis, M, Dovia, C, Doyle, A, Dragojevic, I, Drenth, J, Duan, X, Dulskas, A, Dumitrascu, D, Duncan, O, Dusabejambo, V, Dwawhi, R, Eiketsu, S, El Amrousy, D, El Deeb, A, El Deriny, G, El Din, H, El Kamshishy, S, El Kassas, M, El Raziky, M, Elagamy, O, Elakel, W, Elalfy, D, Elaraby, H, Elawady, H, Elbadawy, R, Eldash, H, Eldefrawy, M, Elecharri, C, Elfaramawy, A, Elfatih, M, Elfiky, M, Elgamsy, M, Elgendy, M, El-Guindi, M, Elhussieny, N, Eliwa, A, Elkabbany, Z, El-Khayat, H, El-Koofy, N, Elmetwalli, A, Elrabat, A, El-Raey, F, Elrashdy, F, Elsahhar, M, Elsaid, E, Elsayed, S, Elsayed, H, Elsayed, A, El-Serafy, M, Elsharkawy, A, Elsheemy, R, Elshemy, E, Elsherbini, S, Eltoukhy, N, Elwakil, R, Emad, O, Emad, S, Embabi, M, Ergenc, I, Ermolova, T, Esmat, G, Esmat, D, Estupinan, E, Ettair, S, Eugen, T, Ezz-Eldin, M, Falcon, L, Fan, Y, Fandari, S, Farag, M, Farahat, T, Fares, E, Fares, M, Fassio, E, Fathy, H, Fathy, D, Fathy, W, Fayed, S, Feng, D, Feng, G, Fernandez-Bermejo, M, Ferreira, C, Ferrer, J, Forbes, A, Fouad, R, Fouad, H, Frisch, T, Fujii, H, Fukunaga, S, Fukunishi, S, Fulya, H, Furuhashi, M, Gaber, Y, Galang, A, Gallardo, J, Galloso, R, Gamal, M, Gamal, R, Gamal, H, Gan, J, Ganbold, A, Gao, X, Garas, G, Garba, T, Garcia-Cortes, M, Garcia-Monzon, C, Garcia-Samaniego, J, Gastaldelli, A, Gatica, M, Gatley, E, Gegeshidze, T, Geng, B, Ghazinyan, H, Ghoneem, S, Giacomelli, L, Giannelli, G, Giannini, E, Giefer, M, Gines, P, Girala, M, Giraudi, P, Goh, G, Gomaa, A, Gong, B, Gonzales, D, Gonzalez, H, Gonzalez-Huezo, M, Graupera, I, Grgurevic, I, Gronbaek, H, Gu, X, Guan, L, Gueye, I, Guingane, A, Gul, O, Gul, C, Guo, Q, Gupta, P, Gurakar, A, Gutierrez, J, Habib, G, Hafez, A, Hagman, E, Halawa, E, Hamdy, O, Hamed, A, Hamed, D, Hamid, S, Hamoudi, W, Han, Y, Haridy, J, Haridy, H, Harris, D, Hart, M, Hasan, F, Hashim, A, Hassan, I, Hassan, A, Hassan, E, Hassan, M, Hassanin, F, Hassnine, A, Haukeland, J, Hawal, A, He, J, He, Q, He, Y, He, F, Hegazy, M, Hegazy, A, Henegil, O, Hernandez, N, Hernandez-Guerra, M, Higuera-de-la-Tijera, F, Hindy, I, Hirota, K, Ho, L, Hodge, A, Hosny, M, Hou, X, Huang, J, Huang, Y, Huang, Z, Huang, A, Huang, X, Hui-ping, S, Hunyady, B, Hussein, M, Hussein, O, Hussien, S, Ibanez-Samaniego, L, Ibdah, J, Ibrahim, L, Ibrahim, M, Ibrahim, I, Icaza-Chavez, M, Idelbi, S, Idilman, R, Ikeda, M, Indolfi, G, Invernizzi, F, Irshad, I, Isa, H, Iskandar, N, Ismaiel, A, Ismail, M, Ismail, Z, Ismail, F, Iwamoto, H, Jack, K, Jacob, R, Jafarov, F, Jafri, W, Jahshan, H, Jalal, P, Jancoriene, L, Janicko, M, Jayasena, H, Jefferies, M, Jha, V, Ji, F, Ji, Y, Jia, J, Jiang, C, Jiang, N, Jiang, Z, Jin, X, Jin, Y, Jing, X, Jingyu, Q, Jinjolava, M, Jong, F, Jucov, A, Julius, I, Kaddah, M, Kamada, Y, Kamal, A, Kamal, E, Kamel, A, Kao, J, Karin, M, Karlas, T, Kashwaa, M, Katsidzira, L, Kaya, E, Kayasseh, M, Keenan, B, Keklikkiran, C, Keml, W, Khalaf, D, Khalefa, R, Khamis, S, Khater, D, Khattab, H, Khavkin, A, Khlynova, O, Khmis, N, Kobyliak, N, Koffas, A, Koike, K, Kok, K, Koller, T, Komas, N, Korochanskaya, N, Koulla, Y, Koya, S, Kraft, C, Kraja, B, Krawczyk, M, Kuchay, M, Kulkarni, A, Kumar, A, Kumar, M, Lakoh, S, Lam, P, Lan, L, Lange, N, Lankarani, K, Lanthier, N, Lapshyna, K, Lashen, S, Laure, K, Lazebnik, L, Lebrec, D, Lee, S, Lee, W, Lee, Y, Leeming, D, Leite, N, Leon, R, Lesmana, C, Li, J, Li, Q, Li, Y, Li, L, Li, M, Liang, H, Lijuan, T, Lim, S, Lim, L, Lin, S, Lin, H, Lin, R, Lithy, R, Liu, Y, Liu, X, Liu, W, Liu, S, Liu, K, Liu, T, Lonardo, A, Lopez, M, Lopez-Benages, E, Lopez-Jaramillo, P, Lu, H, Lu, L, Lu, Y, Lubel, J, Lui, R, Lupasco, I, Luzina, E, Lv, X, Lynch, K, Ma, H, Machado, M, Maduka, N, Madzharova, K, Magdaong, R, Mahadeva, S, Mahfouz, A, Mahmood, N, Mahmoud, E, Mahrous, M, Maiwall, R, Majeed, A, Majumdar, A, Mak, L, Maklouf, M, Malekzadeh, R, Mandato, C, Mangia, A, Mann, J, Mansour, H, Mansouri, A, Mantovani, A, Mao, J, Maramag, F, Marchesini, G, Marcus, C, Marinho, R, Martinez-Chantar, M, Martins, A, Marwan, R, Mason, K, Masoud, G, Massoud, M, Matamoros, M, Mateos, R, Mawed, A, Mbanya, J, Mbendi, C, Mccolaugh, L, Mcleod, D, Medina, J, Megahed, A, Mehrez, M, Memon, I, Merat, S, Mercado, R, Mesbah, A, Meskini, T, Metwally, M, Metwaly, R, Miao, L, Micah, E, Miele, L, Milivojevic, V, Milovanovic, T, Mina, Y, Mishkovik, M, Mishriki, A, Mitchell, T, Mohamed, A, Mohamed, M, Mohamed, S, Mohammed, S, Mohammed, A, Mohan, V, Mohie, S, Mokhtar, A, Moniem, R, Montilla, M, Morales, J, Morata, M, Moreno-Planas, J, Morise, S, Mosaad, S, Moselhy, M, Mostafa, A, Mostafa, E, Mouane, N, Mousa, N, Moustafa, H, Msherif, A, Muller, K, Munoz, C, Munoz-Urribarri, A, Murillo, O, Mustapha, F, Muzurovic, E, Nabil, Y, Nafady, S, Nagamatsu, A, Nakajima, A, Nakano, D, Nan, Y, Nascimbeni, F, Naseef, M, Nashat, N, Natalia, T, Negro, F, Nersesov, A, Neuman, M, Ng'Wanasayi, M, Ni, Y, Nicoll, A, Niizeki, T, Nikolova, D, Ningning, W, Niriella, M, Nogoibaeva, K, Nordien, R, O Sullivan, C, O'Beirne, J, Obekpa, S, Ocama, P, Ochwoto, M, Ogolodom, M, Ojo, O, Okrostsvaridze, N, Oliveira, C, Omana, R, Omar, O, Omar, H, Omar, M, Omran, S, Omran, R, Osman, M, Owise, N, Owusu-Ansah, T, Padilla- Machaca, P, Palle, S, Pan, Z, Pan, X, Pan, Q, Papaefthymiou, A, Paquissi, F, Par, G, Parkash, A, Payawal, D, Peltekian, K, Peng, X, Peng, L, Peng, Y, Pengoria, R, Perez, M, Perez, J, Perez, N, Persico, M, Pessoa, M, Petta, S, Philip, M, Plaz Torres, M, Polavarapu, N, Poniachik, J, Portincasa, P, Pu, C, Purnak, T, Purwanto, E, Qi, X, Qian, Z, Qiang, Z, Qiao, Z, Qiao, L, Queiroz, A, Rabiee, A, Radwan, M, Rahetilahy, A, Ramadan, Y, Ramadan, D, Ramli, A, Ramm, G, Ran, A, Rankovic, I, Rao, H, Raouf, S, Ray, S, Reau, N, Refaat, A, Reiberger, T, Remes-Troche, J, Reyes, E, Richardson, B, Ridruejo, E, Riestra Jimenez, S, Rizk, I, Roberts, S, Roblero, J, Robles, J, Rockey, D, Rodriguez, M, Rodriguez Hernandez, H, Roman, E, Romeiro, F, Romeo, S, Rosales-Zabal, J, Roshdi, G, Rosso, N, Ruf, A, Ruiz, P, Runes, N, Ruzzenente, A, Ryan, M, Saad, A, Sabbagh, E, Sabbah, M, Saber, S, Sabrey, R, Sabry, R, Saeed, M, Said, D, Said, E, Sakr, M, Salah, Y, Salama, R, Salama, A, Saleh, H, Saleh, A, Salem, A, Salifou, A, Salih, A, Salman, A, Samouda, H, Sanai, F, Sanchez-Avila, J, Sanker, L, Sano, T, Sanz, M, Saparbu, T, Sawhney, R, Sayed, F, Sayed, S, Sayed, A, Sayed, M, Sebastiani, G, Secadas, L, Sediqi, K, Seif, S, Semida, N, Senates, E, Serban, E, Serfaty, L, Seto, W, Sghaier, I, Sha, M, Shabaan, H, Shalaby, L, Shaltout, I, Sharara, A, Sharma, V, Shawa, I, Shawkat, A, Shawky, N, Shehata, O, Sheils, S, Shewaye, A, Shi, G, Shi, J, Shimose, S, Shirono, T, Shou, L, Shrestha, A, Shui, G, Sievert, W, Sigurdardottir, S, Sira, M, Siradj, R, Sison, C, Smyth, L, Soliman, R, Sollano, J, Sombie, R, Sonderup, M, Sood, S, Soriano, G, Stedman, C, Stefanyuk, O, Stimac, D, Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease
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Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,Hepatology ,Non-alcoholic Fatty Liver Disease ,NAFLD ,consensu ,Gastroenterology ,MAFLD ,definition ,Humans ,MAFLD, NAFLD ,Human medicine - Abstract
Contains fulltext : 252162.pdf (Publisher’s version ) (Closed access)
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- 2022
3. Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH
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Moisés Diago, Manuel Hernández-Guerra, Agustín Albillos, Rafael Bañares, Esther Molina, María Teresa Arias-Loste, Pere Ginès, Manuel Romero-Gómez, María Jesús Pareja, Joaquín Cabezas, Anna Lligoña, Santiago Tomé, Rocío Gallego, Javier Abad, Joan Genescà, Ramon Bataller, Juan Caballería, Ramon Planas, Rocío Aller, Javier Salmerón, F. Jorquera, José A. Carrión, José Altamirano, Carmelo García-Monzón, Meritxell Ventura-Cots, Miren García-Cortés, Conrado M Fernández Rodríguez, and Llorenç Caballería
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Gastroenterology ,Alcoholic hepatitis ,Disease ,medicine.disease ,Chronic liver disease ,Liver disease ,Internal medicine ,medicine ,Prednisolone ,Steatohepatitis ,Intensive care medicine ,business ,medicine.drug - Abstract
Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.
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- 2019
4. CRIVALVIR-FOCUS: low HIV and chronic Hepatitis B and C infection prevalence among women in reproductive and sexual health services in Valencia, Spain
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Miguel Garcia-Deltoro, Pilar Obon, Caterina Canapele, Jose Maria Mari, Adela Vidal, Maria Martinez-Roma, Maria Dolores Ocete, Concepción Gimeno Cardona, Moisés Diago, Neus Gomez-Muñoz, Alba Carrodeguas, Diogo Medina, and Enrique Ortega González
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Hepatology - Published
- 2022
5. Hepatitis B surface antigen loss after discontinuing nucleos(t)ide analogue for treatment of chronic hepatitis B patients is persistent in White patients
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Rosa Maria Morillas, Juan Arenas Ruiz Tapiador, Javier Crespo, Rafael Gómez-Rodríguez, Manuel Rodríguez, José Manuel Zozaya, Marta Casado, Juan Manuel Pascasio-Acevedo, Miguel Angel Simón, J. Fuentes, Martín Prieto, Blanca Figueruela, Jose Luis Calleja, Maria Buti, Moisés Diago, T. Casanovas, E. Suárez, and Esther Molina
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Male ,HBsAg ,Time Factors ,Cirrhosis ,Hepatocellular carcinoma ,medicine.medical_treatment ,Liver transplantation ,medicine.disease_cause ,Chronic hepatitis B ,Gastroenterology ,Nucleos(t)ide analogue treatment ,0302 clinical medicine ,Recurrence ,Risk Factors ,Hepatitis B virus reactivation ,Nucleotides ,Remission Induction ,Nucleosides ,Middle Aged ,Hepatitis B ,Treatment Outcome ,Hepatitis B surface antigen ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Adult ,Hepatitis B virus ,medicine.medical_specialty ,Antiviral Agents ,Drug Administration Schedule ,White People ,03 medical and health sciences ,Hepatitis B, Chronic ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,medicine.disease ,digestive system diseases ,Discontinuation ,Spain ,Elevated transaminases ,business ,Biomarkers - Abstract
OBJECTIVE: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment. BACKGROUND: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients. PATIENTS AND METHODS: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8-54.6 months). RESULTS: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation. CONCLUSION: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis.
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- 2019
6. Eight weeks of Paritaprevir/r/Ombitasvir + Dasabuvir in HCV genotype 1b with mild-moderate fibrosis: Results from a real-world cohort
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José A. Carrión, Juan Turnes, J.M. Moreno, Esther Molina, M. Puigvehí, José María Moreno, Joaquín Cabezas, Juan de la Vega, Jose Luis Castro, Rosa Maria Morillas, Jose Luis Calleja, Sabela Lens, Beatriz de Cuenca, Javier Salmerón, J.J. Sanchez-Ruano, Ester Badia, M. D. Anton, Silvia Montoliu, P. Cordero, Moisés Diago, Xavier Torras, Juan Manuel Pascasio, Antonio Olveira, F. Gea, Ana Viu, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, and European Commission
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Cyclopropanes ,Liver Cirrhosis ,Male ,Sustained Virologic Response ,Paritaprevir ,Hepacivirus ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,Medicine ,Anilides ,Prospective Studies ,Aged, 80 and over ,Sulfonamides ,Dasabuvir ,Valine ,Middle Aged ,Viral Load ,Sustained virological response ,030220 oncology & carcinogenesis ,Cohort ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Viral load ,medicine.drug ,Adult ,medicine.medical_specialty ,Macrocyclic Compounds ,Genotype ,Proline ,Lactams, Macrocyclic ,Antiviral Agents ,Young Adult ,03 medical and health sciences ,Internal medicine ,Humans ,Uracil ,Aged ,Hepatology ,business.industry ,Hepatitis C, Chronic ,Ombitasvir ,Discontinuation ,Regimen ,chemistry ,Spain ,Ritonavir ,Carbamates ,business - Abstract
[Background & Aims] The interferon‐free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV /r/OBV /DSV ) has shown high efficacy in patients with hepatitis C virus (HCV ) genotype 1b infection when administered for 8 or 12 weeks, but data regarding the 8‐week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8‐week administration of PTV /r/OBV /DSV in a real‐world cohort., [Methods] We performed a multicentre observational study from Spanish Hepa‐C database including patients receiving 8 weeks of PTV /r/OBV /DSV (October 2016‐November 2017). Those with advanced fibrosis, with non‐genotype 1b or who were treatment‐experienced were excluded., [Results] A total of 211 patients were registered from 23 Spanish centres; eleven were excluded. At baseline, 42.5% (n = 85) were male, median (range) age was 57 (23‐86), ALT was 45 (11‐494) IU/mL, viral load was 6.1 (3.3‐8.2) log10 IU/mL, and 74.5% had mild liver fibrosis (F0‐F1) and 25.5% moderate fibrosis (F2). At the end of treatment (EOT ), HCV viral load was undetectable in 100% (200/200). Seven patients relapsed after treatment discontinuation. Sustained virological response (SVR 12) rates by intention‐to‐treat analysis were 96% (192/200). Regarding treatment safety, 2 patients developed ALT elevation >5x ULN, but there were no treatment discontinuations. One patient died 7 weeks after EOT., [Conclusion] Treatment with PTV/r/OBV/DSV in genotype 1b‐infected treatment‐naive patients with mild‐moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT 03122132., JAC has received a grant from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI14/00540), co‐funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa.
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- 2018
7. One-step diagnosis strategy together with multidisciplinary telematics referral perform an effective approach for identifying and treating patients with active Hepatitis C infection
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Enrique Ortega González, Purificación Rubio Cuevas, Miguel García-Deltoro, Neus Gómez-Muñoz, Moisés Diago Madrid, Miriam Torrecillas, María Dolores Ocete, and Concepción Gimeno Cardona
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Male ,Care process ,medicine.medical_specialty ,Referral ,Hepatitis C virus ,Specialties of internal medicine ,Viremia ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Serology ,Multidisciplinary approach ,Interquartile range ,Internal medicine ,HCV-cAg ,medicine ,Telematics referral ,Humans ,One-step ,Active hepatitis ,Hepatology ,business.industry ,Two-step ,General Medicine ,Hepatitis C Antibodies ,medicine.disease ,Hepatitis C ,Telemedicine ,RC581-951 ,Female ,Hepatitis C Antigens ,business - Abstract
Introduction and objectives Implementation of a one-step strategy for diagnosis of active Hepatitis C virus (HCV) infection would encourage the early diagnosis and reduce the time to access antiviral treatments. The aim of this study was to evaluate the impact of a HCV one-step diagnosis compared to the traditional two-step protocol in terms of the time required for patients to be seen by specialists and the time taken to start antiviral treatment. Material and methods A comparative study was carried out to assess two diagnostic algorithms (one-step and two-step) for active HCV infection. Serological markers were quantified using the same serum sample to determine both anti-HCV antibodies (HCV-Ab) and HCV core antigen (HCV-cAg) by Architect i2000 SR kit. In this period, a multidisciplinary procedure was started for telematics referral of viremic patients. Results One-step approach reduced the time required for patient HCV diagnosis, referral to a specialist, access to treatment, and eliminated the loss of patients to follow-up. Significant differences were observed between one-step and two-step diagnosis methods in the time required for patients to be seen by a specialist (18 days [Interquartile range (IQR) = 14–42] versus 107 days [IQR = 62–148]) and for the initiation of treatment (54 days [IQR = 43–75] versus 200 days [IQR = 116–388]), mainly for patients with advanced fibrosis (35 days [IQR = 116–388] versus 126 days [IQR = 152–366]). Conclusions Use of HCV-cAg has proven to be a useful tool for screening patients with active hepatitis C. The development of a multidisciplinary protocol for the communication of results improved the efficiency of the care process.
- Published
- 2021
8. Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis : A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects
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Javier Salmerón, Rosa Martin-Mateos, Salvador Augustin, Conrado M. Fernández-Rodríguez, Javier Crespo, José Miguel Rosales, Desam Escudero, Judith Gómez-Camarero, Joan Caballería, María Jesús Pareja‐Megia, HEPAmet Registry, Rosa Maria Morillas, Juan Turnes, Jesus M. Banales, Javier Abad, Patricia Aspichueta, Rocío Gallego-Durán, Raquel Latorre, Luis Ibañez, Manuel Romero-Gómez, Javier García-Samaniego, Moisés Diago, Manuel Hernández-Guerra, Salvador Benlloch, Germán Soriano, Águeda González-Rodríguez, Javier Ampuero, Raúl J. Andrade, Oreste Lo Iacono, Rocío Aller, Rubén Francés, Pamela Estévez, Francisco Jorquera, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, and Universidad de Sevilla. Departamento de Medicina
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Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Steatosis ,Biopsy ,Gastroenterology ,digestive system ,Ballooning ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Fatty liver disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,associated fatty liver disease ,Metabolic-associated fatty liver disease ,Humans ,metabolic‐ ,Longitudinal Studies ,First episode ,Inflammation ,Hepatology ,medicine.diagnostic_test ,ballooning, fatty liver disease, inflammation, metabolic-associated fatty liver disease, natural coursesteatohepatitis, steatosis ,business.industry ,Fatty liver ,Natural coursesteatohepatitis ,medicine.disease ,digestive system diseases ,Liver ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Steatohepatitis ,business - Abstract
[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD)., [Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years)., [Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these., [Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death., This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).
- Published
- 2021
9. Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study
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Diana Horta, Mercedes Vergara, Jesús M. González-Santiago, Ana Arencibia, Raúl J. Andrade, Carmen Álvarez-Navascués, Pamela Estévez, Elena Gómez-Domínguez, Carlos Ferre-Aracil, Margarita Sala, Marina Berenguer, Rosa Maria Morillas, Esther Molina, Manuel Hernández-Guerra, Emilio Fábrega, Eva Fernández-Bonilla, Judith Gómez-Camarero, Anna Reig, Albert Parés, Moisés Diago, Victor Vargas, Lander Hijona, Adolfo Gallego-Moya, Nadia Chahri, Francisco Suárez, Agustín Albillos, Conrado M. Fernández-Rodríguez, Indhira M Pérez-Medrano, Manuel Romero-Gómez, Marta Casado, and Gema De la Cruz
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Male ,medicine.medical_specialty ,PROGNOSIS ,Chenodeoxycholic Acid ,PLACEBO-CONTROLLED TRIAL ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fenofibrate ,Internal medicine ,medicine ,Humans ,BIOCHEMICAL RESPONSE ,Adverse effect ,CIRRHOSIS ,Retrospective Studies ,Bezafibrate ,Hepatology ,business.industry ,Liver Cirrhosis, Biliary ,Obeticholic acid ,Middle Aged ,BEZAFIBRATE ,Ursodeoxycholic acid ,eye diseases ,Discontinuation ,URSODEOXYCHOLIC ACID ,Clinical trial ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Alkaline phosphatase ,030211 gastroenterology & hepatology ,Female ,business ,medicine.drug - Abstract
INTRODUCTION: Obeticholic acid (OCA) and fibrates therapy results in biochemical improvement in placebo-controlled trials in patients with primary biliary cholangitis and insufficient response to ursodeoxycholic acid. There is scarce information outside of clinical trials. Therefore, we have assessed the effectiveness and adverse events of these treatments. METHODS: Data from patients included in the ColHai registry treated with OCA, fibrates, or both were recorded during a year, as well as adverse events and treatment discontinuation. RESULTS: Eighty-six patients were treated with OCA, 250 with fibrates (81% bezafibrate; 19% fenofibrate), and 15 with OCA plus fibrates. OCA group had baseline significantly higher alkaline phosphatase (ALP) (P = 0.01) and lower platelets (P = 0.03) than fibrates. Both treatments significantly decreased ALP, gamma-glutamyl transferase (GGT), and transaminases and improved Globe score. Albumin and immunoglobulin type M improved in the fibrates group. ALP decrease was higher under fibrates, whereas alanine aminotransferase decline was higher under OCA. Although baseline transaminases and GGT were higher in patients with OCA plus fibrates, significant ALP, GGT, alanine aminotransferase, and Globe score improvement were observed during triple therapy. Adverse events were reported in 14.7% of patients (21.3% OCA; 17.6% fenofibrate; 10.7% bezafibrate), mainly pruritus (10.1% with OCA). Discontinuation was more frequent in fenofibrate treatment mainly because of intolerance or adverse events. DISCUSSION: Second-line therapy with OCA or fibrates improves hepatic biochemistry and the GLOBE score in primary biliary cholangitis patients with suboptimal response to ursodeoxycholic acid. Simultaneous treatment with OCA and fibrates improved ALP as well.
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- 2021
10. Erratum to: 'Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH (J Hepatol 2020; 73: 17-25)
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Agustín Albillos, Juan Turnes, Joan Caballería, Germán Soriano, Javier García-Samaniego, Salvador Augustin, HEPAmet Registry, Jesus M. Banales, Manuel Romero-Gómez, Rocío Gallego-Durán, Rosa Maria Morillas, Francisco Jorquera, Patricia Aspichueta, Pamela Estévez, Luis Ibañez, José Miguel Rosales, Moisés Diago, Javier Salmerón, Raquel Latorre, Rocío Aller, Jose Luis Calleja, Salvador Benlloch, Raúl J. Andrade, Manuel Hernández-Guerra, Javier Ampuero, Oreste Lo Iacono, Conrado M. Fernández-Rodríguez, Desamparados Escudero, Carmelo García-Monzón, Judith Gómez-Camarero, Javier Crespo, and Rubén Francés
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Pediatrics ,medicine.medical_specialty ,Hepatology ,New onset diabetes ,business.industry ,Published Erratum ,medicine ,MEDLINE ,Mistake ,In patient ,business ,Publication process ,Significant fibrosis - Abstract
It has come to our attention that there was a mistake in Fig. 2 in the published version of our manuscript. The mistake occurred during the publication process and has resulted in the lines being absent from the Kaplan-Meier plots in Fig. 2A,B. The y-axis was also incorrectly labelled in Fig. 2B. Please see the corrected figure below. We apologize for any inconvenience caused. This has been corrected in the online version. [Figure presented]
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- 2020
11. Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH
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Francisco Jorquera, Luis Ibañez, Javier Crespo, Carmelo García-Monzón, Manuel Hernández Guerra, Patricia Aspichueta, Javier García-Samaniego, Raquel Latorre, Pamela Estévez, Salvador Augustin, HEPAmet Registry, Javier Ampuero, Conrado M. Fernández-Rodríguez, Judith Gómez-Camarero, Salvador Benlloch, Desamparados Escudero, Raúl J. Andrade, Joan Caballería, Agustín Albillos, José Miguel Rosales, Manuel Romero Gómez, Moisés Diago, Rubén Francés, Rosa Maria Morillas, Rocío Aller, Oreste Lo Iacono, Juan Turnes, Germán Soriano, Rocío Gallego-Durán, Jose Luis Calleja, Jesus M. Banales, Javier Salmerón, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, and Gilead Sciences
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0301 basic medicine ,Arterial hypertension ,medicine.medical_specialty ,Gastroenterology ,digestive system ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Fibrosis ,Internal medicine ,NAFLD ,Biopsy ,medicine ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fatty liver ,Hypertriglyceridemia ,Type 2 Diabetes Mellitus ,nutritional and metabolic diseases ,medicine.disease ,Hepamet score ,digestive system diseases ,030104 developmental biology ,Liver biopsy ,030211 gastroenterology & hepatology ,business ,Dyslipidemia - Abstract
[Background & Aims] Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients., [Methods] We included 178 metabolically healthy—defined by the absence of baseline T2DM, AHT, dyslipidemia—patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia., [Results] During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19–7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14–5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS, [Conclusion] Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM., [Lay summary] Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus., This project has been partially funded by the “Consejería de Salud de la Junta de Andalucía” (PI-0075-2014), the “Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III” (PI19/01404, PI16/01842 and PI17/00535) and “Gilead” (GLD19/00100).
- Published
- 2020
12. Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica
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Javier Abad, Jordi Muntané, Joan Caballería, Javier Crespo, Elsa Solà, Conrado M. Fernández-Rodríguez, Manuel Hernández-Guerra, Agustín Albillos, Javier Salmerón, Francisco Jorquera, Manuel Romero-Gómez, María Jesús Pareja, Maria Reig, Rafael Bañares, Llorenç Caballería, María Teresa Arias-Loste, José López Miranda, Joan Genescà, Oreste Lo Iacono, E. Vilar-Gomez, Manuel Rodríguez-Perálvarez, Rocío Aller, J.M. Navarro, Rocío Gallego, Marina Berenguer, José A. Carrión, Carmelo García-Monzón, Miguel Ángel Rojo, Miren García-Cortés, Ramon Bataller, Esther Molina, and Moisés Diago
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medicine.medical_specialty ,Hepatology ,Mediterranean diet ,business.industry ,medicine.medical_treatment ,Fatty liver ,Gastroenterology ,nutritional and metabolic diseases ,Type 2 diabetes ,Disease ,Liver transplantation ,medicine.disease ,digestive system ,Obesity ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Steatosis ,medicine.symptom ,business - Abstract
Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville.
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- 2018
13. Impact of comorbidities on patient outcomes after interferon-free therapy-induced viral eradication in hepatitis C
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Martin Bonacci, Aida Ortega-Alonso, Jose Luis Calleja, Manuel de la Mata, Raúl J. Andrade, Maria Buti, Guillermo Ontanilla, Juan José Urquijo, Javier Crespo, Juan Manuel Pascasio, Carlota Jimeno, José María Moreno-Planas, José Miguel Rosales, Nieves Palomo, Xavier Forns, Isabel Carmona, Marta Hernández, Blanca Figueruela, Francisco Javier Serrano, Manuel Romero-Gómez, M. Maraver, Javier Salmerón, Ángela Rojas, Javier Ampuero, R. Quiles, Susana Llerena, P. Cordero, J.M. Navarro, and Moisés Diago
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Male ,medicine.medical_specialty ,Cirrhosis ,Survival ,Sustained Virologic Response ,Bilirubin ,Charlson index ,Comorbidity ,Antiviral Agents ,Models, Biological ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Prospective Studies ,Stage (cooking) ,Aged ,Proportional Hazards Models ,Hepatology ,business.industry ,Hazard ratio ,Viral eradication ,Hepatitis C ,Middle Aged ,Prognosis ,medicine.disease ,chemistry ,Spain ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,030211 gastroenterology & hepatology ,Liver function ,business ,Algorithms - Abstract
Background & Aims: Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of directacting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model. Methods: This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes. Results: A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, ChildPugh 0.72, CirCom 0.68) regarding one-and two-year mortality. HepCom score identified low- (= 25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups. Conclusions: The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one-and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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- 2018
14. Sa349 A GLOBAL SURVEY OF PHYSICIANS KNOWLEDGE ABOUT NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
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Janus Ong, Marco Arrese, Saleh A. Alqahtani, Zobair M. Younossi, Moisés Diago, Brian Lam, Manuel Romero-Gómez, Marcelo Kugelmas, Wah-Kheong Chan, Linda Henry, Issah Younossi, Andrei Racila, Jacob George, Laurent Castera, Ming-Hua Zheng, Patrizia Burra, Vincent Wai-Sun Wong, Saeed Hamid, Mohammed El Kassas, Elisabetta Bugianesi, Maria Buti, Khalid Alswat, Nahum Méndez-Sánchez, Yusuf Yilmaz, Ajay Duseja, Yuichiro Eguchi, Hirokazu Takahashi, Jian-Gao Fan, Mariam Ziayee, Maria Stepanova, and George V. Papatheodoridis
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medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Fatty liver ,Gastroenterology ,medicine ,Non alcoholic ,Disease ,medicine.disease ,business - Published
- 2021
15. Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease
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José Ramón Fernández, Jose Luis Calleja, J. Llaneras, V. Hontangas, J. Fuentes, J.J. Sanchez-Ruano, José María Moreno, Xavier Forns, Rosa Maria Morillas, Lucia Bonet, Juan de la Vega, Carmen Baliellas, Moisés Diago, Susana Llerena, Esther Molina, Maria Cuaresma, M.A. Simón, Mercè Roget, Sergio Rodríguez-Tajes, Alicia Hernandez-Albujar, B. Sacristan, Xavier Torras, Conrado M. Fernández-Rodríguez, Pilar Sánchez Pobre, José A. Carrión, Oreste Lo lacono, Mercedes Vergara, Federico Sáez-Royuela, Mari Carmen Navascués, Sabela Lens, Carmen Lopez, Inmaculada Fernández, Jose Ramon Salcines, Raúl J. Andrade, Montserrat Forné, Miguel Fernández Bermejo, Silvia Montoliu, and Gloria Sánchez Antolín
- Subjects
Male ,medicine.medical_specialty ,Cirrhosis ,DACLATASVIR PLUS ASUNAPREVIR ,COMPENSATED CIRRHOSIS ,Health Services for the Aged ,Population ,Hepacivirus ,VIRUS-INFECTION ,Antiviral Agents ,Severity of Illness Index ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,GENOTYPE 1B ,030212 general & internal medicine ,education ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,AGED 65 YEARS ,education.field_of_study ,Hepatology ,business.industry ,Ribavirin ,HCV INFECTION ,Gastroenterology ,Hepatitis C ,Hepatitis C, Chronic ,Viral Load ,EFFICACY ,medicine.disease ,chemistry ,Tolerability ,Spain ,SAFETY ,Concomitant ,Female ,030211 gastroenterology & hepatology ,Interferons ,RIBAVIRIN ,business ,CHRONIC HEPATITIS-C - Abstract
OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin
- Published
- 2017
16. Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH
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Moisés Diago, Leon A. Adams, Sacha Lazo-del Vallin, Eduardo Vilar-Gomez, Luis Calzadilla-Bertot, Scott L. Friedman, Licet Gonzalez-Fabian, and Bienvenido Gra-Oramas
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Liver fibrosis ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Fibrosis ,Serum biomarkers ,Internal medicine ,Positive predicative value ,Lifestyle intervention ,Biopsy ,medicine ,Humans ,Platelet ,Hepatology ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Liver ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,sense organs ,Hepatic fibrosis ,business ,Risk Reduction Behavior ,Biomarkers - Abstract
Background & Aims The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. Methods Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. Results Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients, respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P
- Published
- 2017
17. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort
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B. Sacristan, Inmaculada Fernández, Miguel Angel Simón, Xavier Torras, Rosa Maria Morillas, J. Llaneras, Diego Rincón, María García-Eliz, Zoe Mariño, F. Gea, Belén Ruiz-Antorán, Jose Luis Calleja, Carmen A. Navascués, Javier Crespo, Javier García-Samaniego, Francisco Jorquera, Miguel A. Serra, Sabela Lens, Juan Manuel Pascasio, Moisés Diago, R. Muñoz, Conrado M Fernández Rodríguez, Juan Arenas, Susana Llerena, Juan Turnes, Rafael Bañares, Christie Perelló, Javier Ampuero, and Agustín Albillos
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Cyclopropanes ,Male ,Sustained Virologic Response ,Sofosbuvir ,Paritaprevir ,Hepacivirus ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,Anilides ,030212 general & internal medicine ,Chronic ,Aged, 80 and over ,Sulfonamides ,Sustained virologic response ,Dasabuvir ,Liver Neoplasms ,Valine ,Middle Aged ,Hepatitis C ,Genotype 1 ,Treatment Outcome ,Randomized controlled trials ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Uridine Monophosphate ,Ledipasvir ,Glomerular Filtration Rate ,medicine.drug ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Macrocyclic Compounds ,Genotype ,Proline ,Lactams, Macrocyclic ,Antiviral Agents ,Young Adult ,03 medical and health sciences ,Internal medicine ,Ribavirin ,medicine ,Humans ,Uracil ,Aged ,Retrospective Studies ,Fluorenes ,Ritonavir ,Hepatology ,business.industry ,Hepatitis C, Chronic ,Ombitasvir ,Surgery ,Clinical trial ,Antiviral agents ,Real-world ,chemistry ,Spain ,Benzimidazoles ,Carbamates ,Neoplasm Recurrence, Local ,business - Abstract
Background & Aims: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/rito navir plus dasabuvir (OMV/PTV/r + DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. Methods: Data from HCV genotype 1 patients treated with either OMV/PTV/r + DSV +/- ribavirin (RBV) (n = 1567) or LDV/SOF +/- RBV (n = 1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. Results: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV +/- RBV and 95.8% with LDV/SOF +/- RBV. No significant differences were observed in SVR according to HCV subgenotype (p = 0.321 [OMV/PTV/r + DSV +/- RBV] and p = 0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV +/- RBV] and p = 0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p < 0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r + DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. Conclusions: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r + DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. Lay summary: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex. (c) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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- 2017
18. Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease
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Ashley Brown, Piero Luigi Almasio, Lawrence Serfaty, Suzanne Bourgeois, Giovanni Battista Gaeta, Peter Buggisch, Moisés Diago, Ramon Planas, Stefan Zeuzem, Ferenc Szalay, Edmund Omoruyi, I. Lonjon-Domanec, Christophe Hézode, M. Schlag, Y. Horsmans, Ralph DeMasi, Hã©zode, Christophe, Almasio, Piero L., Bourgeois, Stefan, Buggisch, Peter, Brown, Ashley, Diago, Moise, Horsmans, Yve, Serfaty, Lawrence, Szalay, Ferenc, Gaeta, Giovanni B., Planas, Ramon, Schlag, Michael, Lonjon-Domanec, Isabelle, Omoruyi, Edmund, Demasi, Ralph, Zeuzem, Stefan, Hezode C., Almasio P.L., Bourgeois S., Buggisch P., Brown A., Diago M., Horsmans Y., Serfaty L., Szalay F., Gaeta G.B., Planas R., Schlag M., Lonjon-Domanec I., Omoruyi E., DeMasi R., and Zeuzem S.
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Liver Cirrhosis ,Male ,0301 basic medicine ,Simeprevir ,Pyrrolidines ,Cirrhosis ,Sustained Virologic Response ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,Liver disease ,0302 clinical medicine ,Recurrence ,hepatitis C viru ,Multivariate Analysi ,Aged, 80 and over ,Imidazoles ,Valine ,Middle Aged ,RNA, Viral ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Human ,medicine.drug ,Adult ,medicine.medical_specialty ,Daclatasvir ,Genotype ,Logistic Model ,Liver Cirrhosi ,Hepatitis C virus ,simeprevir ,Antiviral Agents ,Viral Relapse ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,daclatasvir ,Adverse effect ,Imidazole ,Aged ,Antiviral Agent ,resistance-associated substitution ,Hepaciviru ,Hepatology ,business.industry ,Hepatitis C, Chronic ,genotype 1b ,medicine.disease ,Virology ,Regimen ,Logistic Models ,030104 developmental biology ,Multivariate Analysis ,Carbamates ,business - Abstract
Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged≥18years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150mg)+daclatasvir (60mg) once daily was administered for 12 or 24weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12weeks of treatment and 64/106 received 24weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.
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- 2017
19. Development and Validation of Hepamet Fibrosis Scoring System-A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis
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Salvador Benlloch, Javier Crespo, Ming-Hua Zheng, Manuel Romero-Gómez, Judith Gómez-Camarero, Juan Turnes, Jesus M. Banales, Miguel Fernández-Bermejo, Rubén Francés, Vlad Ratziu, Patricia Aspichueta, Javier García-Samaniego, Carmelo García-Monzón, Rocío Gallego-Durán, Aurora Giannetti, Javier Salmerón, Conrado M. Fernández-Rodríguez, Jérôme Boursier, Desamparados Escudero, Moisés Diago, Joan Caballería, Eduardo Vilar, Agustín Albillos, Raluca Pais, Germán Soriano, Jose Luis Calleja, Elvira del Pozo Maroto, Javier Ampuero, José Miguel Rosales, M.T.A. Loste, Rocío Aller, Francisco Jorquera, Raúl J. Andrade, Salvatore Petta, Oreste Lo Iacono, Salvador Agustin, Rebeca Sigüenza, Pamela Estévez, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad de Cantabria [Santander], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Ampuero, Javier, Pais, Raluca, Aller, Rocío, Gallego-Durán, Rocío, Crespo, Javier, García-Monzón, Carmelo, Boursier, Jerome, Vilar, Eduardo, Petta, Salvatore, Ming-Hua, Zheng, Escudero, Desamparado, Calleja, Jose Lui, Aspichueta, Patricia, Diago, Moisé, Rosales, Jose Miguel, Caballería, Joan, Gómez-Camarero, Judith, Lo Iacono, Oreste, Benlloch, Salvador, Albillos, Agustín, Turnes, Juan, Banales, Jesus M., Ratziu, Vlad, and Romero-Gómez, Manuel
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Steatosis ,[SDV]Life Sciences [q-bio] ,Biopsy ,Likelihood ratios in diagnostic testing ,Gastroenterology ,Severity of Illness Index ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,Positive predicative value ,Internal medicine ,Nonalcoholic fatty liver disease ,HOMA ,Medicine ,Humans ,ComputingMilieux_MISCELLANEOUS ,Aged ,2. Zero hunger ,NASH, FIBROSIS ,Hepatology ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Prognostic Factor ,Odds ratio ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,Cross-Sectional Studies ,Diagnostic Tool ,Cirrhosis ,Liver ,030220 oncology & carcinogenesis ,Liver biopsy ,Diagnostic odds ratio ,030211 gastroenterology & hepatology ,Female ,business - Abstract
HEPAmet Registry., [Background & Aims] Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis., [Methods] We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n = 768) and validated the system using patients from Cuba (n = 344), Italy (n = 288), France (n = 830), and China (n = 232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios., [Results] Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P = .0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P < .05)., [Conclusions] Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis.
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- 2019
20. Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort
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Conrado M. Fernández-Rodríguez, Fernando Menéndez, Rosa Maria Morillas, Javier García-Samaniego, Juan de la Vega, Ester Badia, Belén Piqueras Alcol, Marta Hernández-Conde, Adolfo Gallego, Inmaculada Fernández, Isabel Carmona, José Luis Castro Urda, Nuria Domínguez García, M. D. Anton, Luisa García Buey, Miguel Fernández-Bermejo, Jose Luis Calleja, José Javier Moreno-Palomares, Francisco J Salmerón, José María Moreno-Planas, Martin Bonacci, Raquel Souto-Rodríguez, Esther Molina, Moisés Diago, José A. Carrión, Jose M Rosales-Zabal, Manuel Romero-Gómez, Silvia Montoliu, Juan Jose Sanchez Ruano, Juan Manuel Pascasio, Blanca Figueruela, Christie Perelló, F. Gea, Susana Llerena, José Castellote, Gilead Sciences, AbbVie Pharmaceuticals, Merck & Co, MSD, BMS College of Engineering, and Janssen Biotech
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Male ,real-world ,Sustained Virologic Response ,Chronic hepatitis C ,law.invention ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine ,030212 general & internal medicine ,Prospective Studies ,Registries ,Aged, 80 and over ,Imidazoles ,Middle Aged ,Drug Combinations ,Infectious Diseases ,Treatment Outcome ,Grazoprevir ,Cohort ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,Female ,Adult ,Elbasvir ,medicine.medical_specialty ,Genotype ,Antiviral Agents ,03 medical and health sciences ,elbasvir/grazoprevir ,Virology ,Internal medicine ,Quinoxalines ,Ribavirin ,Elbasvir, Grazoprevir ,Humans ,chronic hepatitis C ,Adverse effect ,Real‐world ,Aged ,Benzofurans ,Retrospective Studies ,Spain, chronic hepatitis C, elbasvir/grazoprevir, real-world ,Hepatology ,business.industry ,Hepatitis C, Chronic ,Discontinuation ,chemistry ,Elbasvir/grazoprevir ,Spain ,business - Abstract
In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real‐world HCV patient cohort. HEPA‐C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA‐C between December 2016 and May 2017, and treated with EBR/GZR with at least end‐of‐treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19‐92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post‐treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real‐world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.
- Published
- 2019
21. Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs
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Inmaculada Fernández, Maria Buti, Javier García-Samaniego, Zoe Mariño, Manuel Hernández-Guerra, Juan Arenas, Manuel Delgado, Vanesa Bernal, Xavier Torras, Conrado M. Fernández-Rodríguez, Jose Luis Calleja, J. Llaneras, Rafael Esteban, Sabela Lens, José A. Carrión, Moisés Diago, Alba Cachero, Juan Turnes, Ana Arencibia, Mar Riveiro-Barciela, Juan Manuel Pascasio, Miguel Fernández-Bermejo, Rosa Maria Morillas, Silvia Montoliu, Blanca Figueruela, Susana Llerena, F. Gea, Isabel Carmona, Isabel Conde, Ester Badia, Jesús M. González-Santiago, José Miguel Rosales, and Mercedes Iñarrairaegui
- Subjects
Cyclopropanes ,Liver Cirrhosis ,Male ,Aminoisobutyric Acids ,Sofosbuvir ,Sustained Virologic Response ,HCV genotype 3 ,Hepacivirus ,Gastroenterology ,chemistry.chemical_compound ,Velpatasvir ,Sulfonamides ,Dasabuvir ,Hepatitis C ,Middle Aged ,Drug Combinations ,Treatment Outcome ,Tolerability ,Female ,Drug Monitoring ,medicine.drug ,Adult ,medicine.medical_specialty ,Macrocyclic Compounds ,Proline ,Voxilaprevir ,Lactams, Macrocyclic ,Treatment failures ,Antiviral Agents ,Heterocyclic Compounds, 4 or More Rings ,Leucine ,Internal medicine ,Quinoxalines ,Drug Resistance, Viral ,medicine ,Humans ,Hepatology ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,Ombitasvir ,Regimen ,chemistry ,Paritaprevir ,Spain ,Carbamates ,business - Abstract
Background & Aims: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. Methods: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. Results: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevirtr +dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p
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- 2019
22. Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention
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Eduardo Vilar-Gomez, Licet Gonzalez-Fabian, Bienvenido Gra-Oramas, Yadina Martinez-Perez, Ana Torres-Gonzalez, Scott L. Friedman, Manuel Romero-Gómez, Luis Calzadilla-Bertot, Moisés Diago, Ali Yasells-Garcia, and Oscar Villa-Jimenez
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Type 2 diabetes ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Prospective cohort study ,Life Style ,Hepatology ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Fatty liver ,Odds ratio ,Middle Aged ,Models, Theoretical ,medicine.disease ,Confidence interval ,Surgery ,030104 developmental biology ,Liver biopsy ,Multivariate Analysis ,Female ,030211 gastroenterology & hepatology ,business ,Forecasting - Abstract
UNLABELLED Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).
- Published
- 2016
23. Difícil manejo del tratamiento con triple terapia en paciente con hepatitis crónica C y hemodiálisis
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Laura Peño, Juan José Urquijo, Moisés Diago, and Lydia Plana
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0301 basic medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,Hepatology ,business.industry ,Gastroenterology ,Medicine ,030211 gastroenterology & hepatology ,business - Published
- 2017
24. FRI-053-Overlap of primary biliary cholangitis and autoimmune hepatitis. Natural history and prognosis in a large cohort of patients from Spain
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Mercedes Vergara Gómez, Emilio Fábrega, Agustín Albillos, Elena Gómez Domínguez, Manuel Hernández Guerra, Diana Horta, Margarita Sala, Adolfo Gallego Moya, Albert Parés, Anna Reig, Andrés Castaño-García, Moisés Diago, Nadia Chahri, Jesús M. González-Santiago, Carlos Ferre, Javier Salmerón, Conrado M Fernández Rodríguez, Pamela Estévez, Laura Patricia Llovet, José A. Carrión, Federico Sáez-Royuela, Eva Fernandez Bonilla, Manuel Romero Gomez, Raúl J. Andrade, and Isabel Conde
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Natural history ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,medicine ,Autoimmune hepatitis ,medicine.disease ,business ,Large cohort - Published
- 2019
25. THU-124-Efficacy and safety of glecaprevir/pibrentasvir for the pangenotypic treatment of chronic hepatitis C in former intravenous drug users: Subanalysis from a Spanish real-world cohort (Hepa-C)
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R. Quiles, Javier Crespo, Vanesa Bernal Monterde, Isabel Carmona, Juan Turnes, Pablo Bellot Garcia, M. Prieto, M. Puigvehí, Manuel Delgado, Juan Manuel Pascasio, Beatriz de Cuenca Morón, Moisés Diago, José Luis Calleja Panero, José A. Carrión, Rosa Maria Morillas, José María Moreno, Xavier Torras, Inmaculada Fernández Vázquez, Miguel Fernández-Bermejo, Lucia Bonet, Juan de la Vega, Lourdes Grande Santamaria, Desamparados Escudero-García, Juan Arenas, M Dolores Anton Conejero, José Juan Moreno, Ana Viu, Agustín Albillos, Jose Miguel Rosales Zabal, Maria Luisa Gutierrez, Carme Baliellas, E. Badia-Aranda, Jesús M. González-Santiago, and Manuel Hernández-Guerra
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medicine.medical_specialty ,Hepatology ,Intravenous drug ,Chronic hepatitis ,business.industry ,HEPA ,Internal medicine ,Cohort ,medicine ,Glecaprevir / pibrentasvir ,business - Published
- 2019
26. PS-200-The combination of HEPAmet fibrosis score and transient elastography shows a high diagnostic accuracy in predicting advanced fibrosis in NAFLD
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Javier Crespo, Javier Ampuero, Juan Turnes, Zheng Ming-Hua, Rubén Francés, Jérôme Boursier, Moisés Diago, Judith Gómez-Camarero, Rocío Gallego-Durán, Salvador Benlloch, Juan Caballería, Rocío Aller, José Luis Calleja Panero, Desamparados Escudero-García, Salvatore Petta, Manuel Romero Gomez, Oreste Lo Iacono, Agustín Albillos, and Salvador Augustin
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medicine.medical_specialty ,Hepatology ,business.industry ,Fibrosis score ,Medicine ,Diagnostic accuracy ,Radiology ,business ,Transient elastography ,Advanced fibrosis - Published
- 2019
27. Low-density lipoprotein and other predictors of response with telaprevir-based therapy in treatment-experienced HCV genotype 1 patients: REALIZE study
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Stanislas Pol, I. Lonjon-Domanec, Thomas Berg, Stefan Zeuzem, Pietro Andreone, Graham R. Foster, Stuart K. Roberts, Moisés Diago, Andrzej Horban, Sandra De Meyer, Ralph DeMasi, R. Focaccia, Zobair M. Younossi, Donghan Luo, Gaston Picchio, Eric Lawitz, Thomas Berg, Pietro Andreone, Stanislas Pol, Stuart Robert, Zobair Younossi, Moises Diago, Eric J. Lawitz, Roberto Focaccia, Graham R. Foster, Andrzej Horban, Isabelle Lonjon-Domanec, Ralph DeMasi, Gaston Picchio, Donghan Luo, Sandra De Meyer, and Stefan Zeuzem
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medicine.medical_specialty ,Multivariate analysis ,Hepacivirus ,Alpha interferon ,predictor ,HEPATITIS C ,LDL ,predictors ,REALIZE ,response ,telaprevir ,Polyethylene Glycols ,Telaprevir ,chemistry.chemical_compound ,Internal medicine ,Ribavirin ,Odds Ratio ,medicine ,Humans ,Hepatology ,biology ,business.industry ,Interferon-alpha ,Hepatitis C ,Odds ratio ,biology.organism_classification ,medicine.disease ,Recombinant Proteins ,Confidence interval ,Lipoproteins, LDL ,Treatment Outcome ,chemistry ,Immunology ,RNA, Viral ,Regression Analysis ,Drug Therapy, Combination ,business ,Oligopeptides ,Biomarkers ,medicine.drug - Abstract
Background & Aims Predictors of response to treatment with peginterferon plus ribavirin are well established. In these post-hoc analyses of the REALIZE study, we sought to identify predictors of response for telaprevir-based triple therapy. Methods Patients from the REALIZE study with baseline data for all predictors evaluated (including baseline disease characteristics and demographics, prior treatment response and baseline laboratory assessments) were included in the post-hoc analyses (n = 465). Univariate and multivariate analyses were used to evaluate factors predicting treatment outcomes. Results Sustained viral response (SVR) rates were 86% in prior relapsers, 63% in prior partial responders and 32% in prior null-responders. In the final multivariate analysis, baseline factors predicting SVR were prior response to treatment [Odds ratio (OR) = 2.80; 95% confidence interval (CI), 2.13–3.69], low-density lipoprotein (LDL) (≥2.6 mmol/L) (OR = 2.11; 95% CI, 1.52–2.93), HCV genotype (OR = 0.58; 95% CI, 0.36–0.93), and maximum alanine amino transferase and aspartate amino transferase (OR = 0.62; 95% CI, 0.40–0.97). Conclusions Prior response to peginterferon plus ribavirin treatment and LDL levels are the main independent predictive markers of response with telaprevir-based triple therapy.
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- 2014
28. High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4
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Álvaro Giráldez, Javier Crespo, Lluis Castells, Juan Manuel Pascasio-Acevedo, Carme Baliellas, Ana Arencibia, Valentín Cuervas-Mons, Xavier Forns, Alejandro Blasco, Joaquín Cabezas, Javier García-Samaniego, Juan Turnes, I. Narváez, V. Hontangas, Montserrat Forné, Adolfo Gallego, Zoe Mariño, Alexandra Gómez, Inmaculada Fernández, J.J. Sanchez-Ruano, Maria Ángeles Castro, Sonia Pascual, Carmen López-Núñez, Martín Prieto, Francisco Gea-Rodríguez, Jose Luis Calleja, José Castellote, José A. Carrión, Xavier Torras, Manuel Romero-Gómez, Moisés Diago, Tomas de Artaza, José Luis Montero, Rosa Maria Morillas, José María Moreno, Gloria Sánchez-Antolín, and Mercedes Vergara
- Subjects
0301 basic medicine ,Simeprevir ,Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,Sofosbuvir ,Hepacivirus ,Gastroenterology ,Antiviral Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,Young Adult ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Registries ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatology ,business.industry ,Ribavirin ,Retrospective cohort study ,Hepatitis C ,Middle Aged ,medicine.disease ,Surgery ,Regimen ,030104 developmental biology ,Treatment Outcome ,chemistry ,Real-life cohort ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P
- Published
- 2017
29. Hepatitis crónica por virus C: pacientes con enfermedad leve
- Author
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Javier García-Samaniego, Raúl J. Andrade, J. Quer, Miguel Angel Simón, Moisés Diago, Rosa Maria Morillas, and Javier Crespo
- Subjects
Simeprevir ,medicine.medical_specialty ,Hepatology ,Sofosbuvir ,business.industry ,Hepatitis C virus ,Ribavirin ,Gastroenterology ,Hepatitis C ,medicine.disease ,medicine.disease_cause ,Telaprevir ,chemistry.chemical_compound ,chemistry ,Pegylated interferon ,Internal medicine ,Boceprevir ,medicine ,business ,medicine.drug - Abstract
Chronic hepatitis C virus infection is usually asymptomatic. The severity of the hepatic lesion in these patients at diagnosis varies and, from the histopathologic point of view, most have mild disease. A series of factors have been described that correlate with the progression of fibrosis in patients with mild fibrosis: age at diagnosis, the duration of the infection, male sex, HIV coinfection, transaminase levels during follow-up, alcohol consumption, metabolic factors such as diabetes and overweight, necroinflammatory activity in the initial biopsy, and the degree of steatosis. In patients with genotype 1 hepatitis C infection, the standard treatment has been pegylated interferon and ribavirin. However, response rates are markedly increased by concomitant use of first-generation protease inhibitors, boceprevir or telaprevir. In patients with moderate fibrosis, these drugs are well tolerated, in addition to being effective. Currently, dual therapy should be reserved for patients with good baseline predictive factors of response and/or contraindications for treatment with telaprevir or boceprevir. In patients with genotypes other than genotype 1, the standard treatment continues to be the combination of pegylated interferon and ribavirin, although the development of new direct-acting antiviral agents such as sofosbuvir and simeprevir will change the strategies used in these patients. The decision to wait for the new treatments is complex because their release date is unknown; likewise, their high cost will limit the possibilities for their use.
- Published
- 2014
30. Fe de errores de «Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica» [Gastroenterol Hepatol. 2018;41(5):328-349]
- Author
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Javier Crespo, Llorenç Caballería, Francisco Jorquera, Miguel Ángel Rojo, Ramon Bataller, José López Miranda, Joan Genescà, Rocío Gallego-Durán, Carmelo García-Monzón, Rafael Bañares, José A. Carrión, J.M. Navarro, Oreste Lo Iacono, Maria Reig, Manuel Romero-Gómez, Conrado M. Fernández-Rodríguez, Moisés Diago, Marina Berenguer, E. Vilar-Gomez, María Jesús Pareja, Rocío Aller, Manuel Rodríguez-Perálvarez, Jordi Muntané, Manuel Hernández-Guerra, Elsa Solà, Esther Molina, Agustín Albillos, Miren García-Cortés, Javier Salmerón, Javier Abad, Joan Caballería, and María Teresa Arias-Loste
- Subjects
Gynecology ,medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,medicine ,MEDLINE ,business - Published
- 2018
31. Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa-2a/ribavirin
- Author
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Stephanos J. Hadziyannis, Mitchell L. Shiffman, A. Lin, Patrick Marcellin, K. Rajender Reddy, Maribel Rodriguez-Torres, Paul J. Pockros, Fernando Tatsch, David I. Bernstein, Moisés Diago, Antonio Craxì, Stefan Zeuzem, and M. Rizzetto
- Subjects
medicine.medical_specialty ,Hepatology ,Receiver operating characteristic ,business.industry ,Ribavirin ,Hepatitis C virus ,virus diseases ,Hepatitis C ,medicine.disease ,Logistic regression ,medicine.disease_cause ,Gastroenterology ,digestive system diseases ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Virology ,Internal medicine ,Genotype ,Immunology ,medicine ,business ,Viral load ,Peginterferon alfa-2a ,medicine.drug - Abstract
Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono-infected and 176 HIV–HCV co-infected patients treated with peginterferon alfa-2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono-infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400 000 IU/mL was used and 16% (59%vs 43%) when 800 000 IU/mL was used. In HIV–HCV genotype 1 co-infected patients, the difference was 51% (71%vs 20%) when 400 000 IU/mL was used and 43% (61%vs 18%) when 800 000 IU/mL was used. A lower threshold (200 000 IU/mL) was identified for genotype 1 mono-infected patients with ‘normal’ alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400 000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1-infected individuals with elevated ALT.
- Published
- 2012
32. Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients
- Author
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María, Buti, Rosa Maria, Morillas, Martín, Prieto, Moisés, Diago, Juan, Pérez, Ricard, Solà, Lucía, Bonet, Antonio, Palau, Milagros, Testillano, Javier, García-Samaniego, Manuel, Rodríguez, and María, Trapero
- Subjects
Adult ,Male ,Hepatitis B virus ,medicine.medical_specialty ,Guanine ,Cirrhosis ,Antiviral Agents ,Gastroenterology ,Hepatitis B, Chronic ,Interquartile range ,Internal medicine ,Humans ,Medicine ,Hepatitis B e Antigens ,Seroconversion ,Adverse effect ,Retrospective Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,Entecavir ,Middle Aged ,Viral Load ,Hepatitis B ,medicine.disease ,Virology ,Treatment Outcome ,HBeAg ,DNA, Viral ,Drug Evaluation ,Female ,business ,Viral load ,medicine.drug - Abstract
BACKGROUND Entecavir is an effective treatment for chronic hepatitis B. However, data from clinical practice are limited, especially in hepatitis B e antigen (HBeAg)-positive patients. METHODS We retrospectively analysed data from 190 nucleos(t)ide-naive chronic hepatitis B patients treated with entecavir (0.5 mg/day) in 25 Spanish centres. Virological response (hepatitis B virus DNA
- Published
- 2012
33. Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response
- Author
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Mojca Matičič, Liliana Chemello, X. Yu, Moisés Diago, J. Torras, R. Faruqi, Antonio Craxì, E. Chaudhri, Eli Zuckerman, M. T. Tartaglione, T. Witthoeft, P. Ogurtsov, Lisa D. Pedicone, and S. Koutsounas
- Subjects
medicine.medical_specialty ,education.field_of_study ,Hepatology ,business.industry ,Ribavirin ,Hepatitis C virus ,Population ,virus diseases ,medicine.disease_cause ,Gastroenterology ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Virology ,Internal medicine ,Immunology ,medicine ,Clinical endpoint ,Peginterferon alfa-2b ,Rapid Virologic Response ,education ,business ,Adverse effect ,Viral load ,medicine.drug - Abstract
Summary. In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load
- Published
- 2011
34. Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin
- Author
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Ángel Carazo, Manuel Romero-Gómez, Antonia Martin-Casares, A. Gila, Paloma Sanz-Cameno, M.A. López-Nevot, Moisés Diago, Ángeles Ruiz-Extremera, Paloma Rueda, J. Casado, Pablo Sáenz-López, Pablo Palomares, Josefa León, Ricardo Moreno-Otero, Esther-José Pavón, José-Antonio Muñoz, R. Quiles, and Javier Salmerón
- Subjects
Adult ,Male ,Genotype ,viruses ,Genes, MHC Class II ,Genes, MHC Class I ,Human leukocyte antigen ,Interferon alpha-2 ,Antiviral Agents ,Polyethylene Glycols ,chemistry.chemical_compound ,Pegylated interferon ,Ribavirin ,medicine ,Humans ,Alleles ,Retrospective Studies ,Hepatology ,business.industry ,Host (biology) ,Interleukins ,Gastroenterology ,Interferon-alpha ,virus diseases ,Hepatitis C, Chronic ,Viral Load ,biochemical phenomena, metabolism, and nutrition ,Virology ,Recombinant Proteins ,digestive system diseases ,Logistic Models ,ROC Curve ,chemistry ,Area Under Curve ,Immunology ,Drug Therapy, Combination ,Female ,Interferons ,business ,medicine.drug - Abstract
Viral factors are considered the best predictors of response to treatment for chronic hepatitis C (CHC), but genetic factors are known to have an important role in this respect. This paper investigates the relationships among the host genetic factors HLA and IL28B, viral factors, and the outcome of combination therapy.A multicenter retrospective cohort of 428 previously untreated CHC patients was treated with pegylated interferon/ribavirin (pegIFN/RBV) for 48 weeks. In all, 378 (88%) of these patients were genotype 1 or 4, and 50 (12%) were genotype 2 or 3.Multivariate logistic regression showed the rs12979860 CC genotype (adjusted odds ratio (aOR)=4.3, 95% confidence interval (95% CI): 2.6-7), the HLA-DQB1*0301 allele (aOR=2.08, 95% CI: 1.2-3.5) and age, viral genotype, and viral load levels to be significantly associated with sustained virological response (SVR). When the variable rs12979860 was eliminated, the area under the receiver operating characteristic (ROC) curve (AUC) decreased significantly (0.76 vs. 0.69; P=0.03). AUC values derived from viral factors were lower than those corresponding to host genetic factors (0.67 vs. 0.72, respectively; P=0.04). The HLA-DQB1*0301 and A*0201 alleles were associated with rs12979860 CC genotype and SVR (P0.0001).The HLA-DQB1*0301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.
- Published
- 2011
35. FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC3 program
- Author
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Steven L. Flamm, Massimo Colombo, Ricardo Moreno-Otero, Louis Griffel, Marcelo Silva, E. Jenny Heathcote, Eugene R. Schiff, Moisés Diago, Navdeep Boparai, Janice K. Albrecht, Fernando L. Gonçales, Thomas Berg, Clifford A. Brass, Warren N. Schmidt, R. Terg, Jordi Bruix, Thierry Poynard, Mona Munteanu, Flair José Carrilho, Antonio Craxì, Thomas J. McGarrity, and Margaret Burroughs
- Subjects
education.field_of_study ,medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,FibroTest ,Ribavirin ,Population ,virus diseases ,Alpha interferon ,Hepatitis C ,medicine.disease ,Gastroenterology ,digestive system diseases ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Immunology ,Biopsy ,Medicine ,business ,education ,Viral load ,Interferon alfa ,medicine.drug - Abstract
Background & Aims EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon–alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. Methods Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. Results Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 ( p p p ⩽0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis ( p ⩽0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). Conclusions FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin.
- Published
- 2011
36. Hepatic steatosis in patients with chronic hepatitis C virus genotype 2 or 3 does not affect viral response in patients treated with peginterferon α-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) for 16 or 24 weeks
- Author
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Karl Barange, Mitchell L. Shiffman, Sugantha Govindarajan, Moisés Diago, Thomas Morgan, A. Lin, Maribel Rodriguez-Torres, Gregory Hooper, Frank Suter, and Bhupinderjit S. Anand
- Subjects
medicine.medical_specialty ,Pathology ,Genotype ,Hepatitis C virus ,Hepacivirus ,Interferon alpha-2 ,medicine.disease_cause ,Gastroenterology ,Polyethylene Glycols ,chemistry.chemical_compound ,Internal medicine ,Ribavirin ,medicine ,Humans ,Univariate analysis ,Hepatology ,business.industry ,Body Weight ,Fatty liver ,Age Factors ,Interferon-alpha ,virus diseases ,Hepatitis C ,Viral Load ,medicine.disease ,Recombinant Proteins ,digestive system diseases ,Fatty Liver ,Logistic Models ,chemistry ,Steatosis ,business ,Viral hepatitis ,Viral load - Abstract
Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear. Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3. Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P
- Published
- 2009
37. Tratamiento de la infección por el virus de la hepatitis C. Estado actual y perspectivas
- Author
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Moisés Diago
- Subjects
Hepatology ,business.industry ,Gastroenterology ,Medicine ,business ,Humanities - Abstract
Resumen El tratamiento actual de los pacientes con hepatitis C cronica es el interferon pegilado y la ribavirina. La aplicacion de la cinetica viral esta permitiendo optimizar el tratamiento variando Ia pauta de 24 semanas para genotipos 2 y 3, y 48 para los demas genotipos. Asi, los pacientes con genotipo 1 con una carga viral baja y una rapida respuesta virologica obtienen una alta respuesta viral sostenida con 24 semanas de tratamiento. Por el contrario, los pacientes respondedores lentos pueden beneficiarse de 72 semanas de tratamiento. Los pacientes con genotipo 2 y 3 tambien pueden beneficiarse de las pautas segun la cinetica viral. En los pacientes no respondedores al tratamiento actual se ha ensayado dosis mas altas y tiempos mas prolongados, aunque para gran numero de ellos no tenemos otra opcion que esperar una nueva generacion de farmacos. El tratamiento de mantenimiento con dosis bajas de interferon para prevenir la cirrosis y/o el hepatocarcinoma esta siendo evaluado.
- Published
- 2008
38. Optical analysis of computed tomography images of the liver predicts fibrosis stage and distribution in chronic hepatitis C
- Author
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Ricard Solà, R Pérez-López, Rafael Aznar, Raúl J. Andrade, Manuel Romero-Gómez, Juan Carlos Alcon, José M. Pérez-Moreno, Victor M. Castellano-Megias, Marina Vera-Valencia, Manuel Fernández-López, A. Madrazo, Emilio Gómez-González, Manuel Nevado-Santos, J.M. Navarro, Luis Rodrigo, Moisés Diago, Ramón Pérez-Álvarez, and Javier Salmerón
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Gastroenterology ,Cohort Studies ,Fibrosis ,Internal medicine ,Image Processing, Computer-Assisted ,medicine ,Humans ,Stage (cooking) ,Aged ,Hepatology ,Receiver operating characteristic ,business.industry ,Histology ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Female ,Tomography, X-Ray Computed ,Hepatic fibrosis ,business - Abstract
This study was undertaken to evaluate an image processing method for assessing liver fibrosis in conventional computed tomography (CT) scans in patients with chronic hepatitis C. Two cohorts (designated “estimation,” n = 34; and “validation,” n = 107) of chronic hepatitis C patients were assessed using digitized conventional helical CT. Weighted CT mean fibrosis (Fibro-CT) was calculated as a nonlinear weighted mean F-score for each sample. Fibrosis was defined according to Scheuer on the F0 to F4 scale by 2 pathologists blinded regarding the Fibro-CT data. Fibrosis according to Fibro-CT correlated with histology-determined fibrosis (r = 0.69; P < 0.001) and with increasing F-stage: F0 = 0.23 ± 0.39; F1 = 0.90 ± 0.99; F2 = 1.41 ± 0.94; F3 = 2.79 ± 0.55; F4 = 3.15 ± 0.35 [analysis of variance: P < 0.0001). The receiver operating characteristics curve to diagnose significant fibrosis (≥F2) was 0.83; 95% confidence interval (95%CI), 0.75 to 0.91; and, to diagnose advanced fibrosis (≥F3), was 0.86, 95%CI: 0.80 to 0.93. The correlation between Fibro-CT and fibrosis was higher in patients with homogeneous distribution of fibrosis than in patients with heterogeneous distribution (r = 0.77 versus r = 0.43; P < 0.05). Conclusion: Optical digital analysis of CT images of the liver is effective in determining the stage and distribution of liver fibrosis in chronic hepatitis C. In patients with homogeneous fibrosis distribution, the correlation between Fibro-CT and histology was better than in patients with heterogeneous distribution. Fibro-CT is a simple to use, readily available, and useful method for the diagnosis of fibrosis in patients with chronic hepatitis C. (HEPATOLOGY 2008.)
- Published
- 2007
39. ¿Mejora el tratamiento antiviral el curso clínico de la cirrosis por virus de la hepatitis C?
- Author
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Moisés Diago
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Hepatitis C virus ,Ribavirin ,Gastroenterology ,Hepatitis C ,medicine.disease_cause ,medicine.disease ,chemistry.chemical_compound ,Maintenance therapy ,chemistry ,Pegylated interferon ,Interferon ,Fibrosis ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Treatment of hepatitis C with pegylated interferon plus ribavirin achieves viral eradication rates of between 50 and 80%. A large number of patients with sustained viral response show fibrosis regression. However, patients without viral response also show improvement. Patients with compensated cirrhosis due to hepatitis C virus can also be successfully treated. In these patients, viral eradication is usually followed by fibrosis non-progression and a reduction of portal hypertension, which undoubtedly modifies the clinical course of the process. In patients without virological response, the ability of antiviral maintenance therapy to alter the natural history of the disease is not clear and three large multicenter studies are currently underway. Preliminary data indicate that patients with cirrhosis treated with interferon as maintenance therapy show less progression than those treated with colchicine.
- Published
- 2007
40. Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis
- Author
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Manuel Romero-Gómez, Eduardo Vilar-Gomez, Maray Socias-Lopez, Leon A. Adams, Ana Torres-Gonzalez, Luis Calzadilla-Bertot, and Moisés Diago
- Subjects
0301 basic medicine ,Blood Glucose ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Hepatitis C virus ,Type 2 diabetes ,medicine.disease_cause ,Gastroenterology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Decompensation ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Hepatology ,business.industry ,Hepatitis C ,Glucose Tolerance Test ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Prognosis ,Liver Transplantation ,Survival Rate ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Disease Progression ,030211 gastroenterology & hepatology ,Female ,Insulin Resistance ,business ,Liver Failure - Abstract
Background Glucose metabolism abnormalities frequently coexist with liver cirrhosis; however, the impact of these on liver-related outcomes has not been fully investigated. Aims We examined the influence of glucose abnormalities on overall mortality and liver-related complications in cirrhotic patients. Methods A prospective cohort of 250 subjects with compensated hepatitis C virus-related cirrhosis and without known diabetes underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks. Results At baseline, 67 (27%) had type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (sHR: 2.2, 95% CI: 1.04–4.6, P = 0.04) and hepatic decompensation events (sHR: 1.9, 95% CI: 1.05–3.3, P = 0.03) were significantly higher in diabetic patients. Subjects with a HOMA-IR >5 showed higher rates of mortality (sHR: 2.2, 95% CI: 1.03–4.8, P = 0.04). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (sHR: 1.7, 95% CI: 1.04–2.9, P = 0.03). Overall, 2h-plasma glucose was the most robust predictor of overall mortality (sHR: 2.5, 95% CI: 1.03–6, P = 0.04) and decompensation (sHR: 2.7, 95% CI: 1.4–5.5, P Conclusions In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival and increased risk of hepatic decompensation.
- Published
- 2015
41. High efficacy and safety of triple therapy in HCV genotype 1 and moderate fibrosis: a multicenter study of clinical practice in Spain
- Author
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Jose Luis Calleja, Javier Crespo, Gloria Sánchez-Antolín, Susana Soto-Fernández, C. Fernández, Manuel Romero-Gómez, Joaquín Cabezas, Federico Sáez-Royuela, Manuel Hernández-Guerra, Antonio Cuadrado, Inmaculada Fernández, Juan José Sánchez, Francisco Jorquera, B. Sacristan, Maria Buti, T. Broquetas, Juan Manuel Pascasio, Carmen López-Núñez, Rosa Maria Morillas, Moisés Diago, Marina Berenguer, Sabela Lens, Javier García-Samaniego, and Miguel A. Serra
- Subjects
Liver Cirrhosis ,Male ,Time Factors ,Specialties of internal medicine ,Hepacivirus ,Gastroenterology ,Severity of Illness Index ,Telaprevir ,Fibrosis ,Risk Factors ,Genotype ,General Medicine ,Middle Aged ,Viral Load ,Treatment Outcome ,RC581-951 ,Hepatitis C genotype 1 ,RNA, Viral ,Drug Therapy, Combination ,Female ,Telaprevir triple therapy ,Moderate fibrosis ,Viral load ,Oligopeptides ,medicine.drug ,Adult ,medicine.medical_specialty ,Antiviral Agents ,Safety and efficacy ,Young Adult ,Internal medicine ,medicine ,Humans ,Adverse effect ,Aged ,Hepatology ,business.industry ,Interleukins ,Hepatitis C, Chronic ,medicine.disease ,Surgery ,Discontinuation ,Clinical trial ,Spain ,Observational study ,Interferons ,business ,Biomarkers - Abstract
Background and rational. Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220). Results. The mean patient age was 55 years, 67% male. Type of prior response was 22% naive, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naive patients (78%) compared with F3/F4-naive patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001). Conclusions. This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.
- Published
- 2015
42. Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities
- Author
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Maria, Buti, Rosa M, Morillas, Juan, Pérez, Martín, Prieto, Ricard, Solà, Antonio, Palau, Moisés, Diago, Lucía, Bonet, Adolfo, Gallego, Javier, García-Samaniego, Milagros, Testillano, Manuel, Rodríguez, Gregorio, Castellano, María L, Gutiérrez, Manuel, Delgado, Antoni, Mas, Manuel, Romero-Gómez, José L, Calleja, Agustina, González-Guirado, Juan I, Arenas, Luisa, García-Buey, Raúl, Andrade, Ana, Gila, and Carmen, Vinaixa
- Subjects
Adult ,Liver Cirrhosis ,Male ,Hepatitis B virus ,medicine.medical_specialty ,Guanine ,drug safety ,Antiviral Agents ,White People ,Young Adult ,Hepatitis B, Chronic ,Chronic hepatitis ,Recurrence ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,chronic hepatitis B ,Hepatitis B e Antigens ,Obesity ,Hepatitis B Antibodies ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,fungi ,Gastroenterology ,Alanine Transaminase ,Entecavir ,Middle Aged ,medicine.disease ,Comorbidity ,clinical practice ,comorbidity ,Creatinine ,DNA, Viral ,Hypertension ,Female ,business ,Follow-Up Studies ,medicine.drug ,entecavir - Abstract
Objectives The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t) ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. Methods We retrospectively analysed data from 237 nucleos(t) ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. Results The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. Conclusion Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
- Published
- 2015
43. Infecciones bacterianas y sistémicas
- Author
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Moisés Diago Madrid and José María Huguet Malavés
- Subjects
Hepatology ,Gastroenterology - Published
- 2006
44. Peginterferon-Alfa2a Plus Ribavirin for 48 Versus 72 Weeks in Patients With Detectable Hepatitis C Virus RNA at Week 4 of Treatment
- Author
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Manuel Romero Gomez, Raúl J. Andrade, Rafael Bárcena, Miguel Muñoz–Sánchez, Manuel García Bengoechea, Javier Crespo, Ramon Perez, Escartin P, J. Samaniego, Moisés Diago, Jaime Enríquez, Ricardo Moreno–Otero, José M. Sánchez Tapias, M. Testillano, Ramon Planas, Eva Martínez Bauer, and Ricard Solà
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hepatitis C virus ,Viremia ,Hepacivirus ,Interferon alpha-2 ,medicine.disease_cause ,Antiviral Agents ,Group A ,Gastroenterology ,Group B ,Polyethylene Glycols ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Internal medicine ,Ribavirin ,medicine ,Humans ,Drug Carriers ,Hepatology ,business.industry ,Incidence (epidemiology) ,Interferon-alpha ,virus diseases ,medicine.disease ,Hepatitis C ,Recombinant Proteins ,digestive system diseases ,Discontinuation ,Treatment Outcome ,chemistry ,Immunology ,RNA, Viral ,Drug Therapy, Combination ,Female ,business ,Follow-Up Studies - Abstract
Background & Aims: Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment. Methods: A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 μg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n=165) or 72 weeks (group B, n=161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment. Results: The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1–infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively ( P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) ( P = .0004). SVR rates in groups C and D were 79% and 64%, respectively. Conclusions: Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.
- Published
- 2006
45. Chronic Hepatitis C in Patients With Persistently Normal Alanine Transaminase Levels
- Author
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Robert Reindollar, Moisés Diago, Paul J. Pockros, Daniele Prati, Steven Blotner, Stefan Zeuzem, Pilar Lardelli, Albert Tran, Maribel Rodriguez–Torres, and Mitchell L. Shiffman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Peginterferon-alfa ,Hepacivirus ,Antiviral Agents ,Severity of Illness Index ,digestive system ,Gastroenterology ,Virus ,chemistry.chemical_compound ,Liver disease ,Liver Function Tests ,Reference Values ,Fibrosis ,Internal medicine ,medicine ,Humans ,Probability ,Randomized Controlled Trials as Topic ,Hepatology ,medicine.diagnostic_test ,biology ,business.industry ,Patient Selection ,Ribavirin ,Alanine Transaminase ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,Titer ,Clinical Trials, Phase III as Topic ,chemistry ,Alanine transaminase ,Case-Control Studies ,Liver biopsy ,DNA, Viral ,Immunology ,Disease Progression ,biology.protein ,Female ,business ,Follow-Up Studies - Abstract
Background & Aims: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). Methods: The characteristics of 480 patients with normal ALT values (on >3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixtyeight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. Results: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P < .01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P < .01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. Conclusions: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.
- Published
- 2006
46. Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C
- Author
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Moisés Diago, Daniele Prati, Paul J. Pockros, Edward Gane, Steven Blotner, Stefan Zeuzem, Patrizia Farci, Pilar Lardelli, Mitchell L. Shiffman, K. Rajender Reddy, and Christopher B. O'Brien
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Hepatitis C virus ,Blood lipids ,Blood Pressure ,Hepacivirus ,Interferon alpha-2 ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Body Mass Index ,Polyethylene Glycols ,chemistry.chemical_compound ,Sex Factors ,Reference Values ,Internal medicine ,Ribavirin ,medicine ,Humans ,Triglycerides ,Metabolic Syndrome ,Hepatology ,biology ,business.industry ,Liver cell ,Interferon-alpha ,Alanine Transaminase ,Hepatitis C, Chronic ,medicine.disease ,Recombinant Proteins ,Metabolism ,Alanine transaminase ,chemistry ,Immunology ,Disease Progression ,Linear Models ,biology.protein ,RNA, Viral ,Drug Therapy, Combination ,Female ,Viral disease ,Metabolic syndrome ,business ,Peginterferon alfa-2a ,medicine.drug - Abstract
Background/Aims In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels. Methods Patients with chronic hepatitis C enrolled in three phase III clinical trials of peginterferon alfa-2a (40KD) plus ribavirin (two studies analysing ‘elevated' and one persistently ‘normal' alanine aminotransferase) were included. Results Multivariate analyses of 2881 patients before treatment and of 1403 patients with a sustained virological response indicated that gender, viral factors (genotype, HCV RNA titer) and indicators of metabolic syndrome (body mass index, blood pressure, blood glucose, cholesterol and triglyceride concentration) were associated with alanine aminotransferase levels. In addition, hepatitis C virus infection influenced serum lipids concentration according to a genotype-specific effect. Conclusions Heterogeneity in alanine aminotransferase levels in patients with chronic hepatitis C partially depends on the degree of derangement of fat and carbohydrate metabolism. As this is the result of an interaction of chronic hepatitis C infection with the patient's individual characteristics, treatment decisions should not be based on alanine aminotransferase level alone but rather on global evaluation of the patient.
- Published
- 2006
47. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels
- Author
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Mitchell L. Shiffman, Norman Gitlin, Moisés Diago, Edward Gane, K. Rajender Reddy, François Lamour, Patrizia Farci, Pilar Lardelli, Paul J. Pockros, Christopher B. O'Brien, Daniele Prati, and Stefan Zeuzem
- Subjects
Adult ,Male ,medicine.medical_specialty ,Combination therapy ,Injections, Subcutaneous ,Hepatitis C virus ,Population ,Interferon alpha-2 ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Polyethylene Glycols ,chemistry.chemical_compound ,Pegylated interferon ,Internal medicine ,Ribavirin ,medicine ,Humans ,education ,education.field_of_study ,Hepatology ,business.industry ,Interferon-alpha ,virus diseases ,Alanine Transaminase ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Recombinant Proteins ,digestive system diseases ,Treatment Outcome ,chemistry ,Relative risk ,Immunology ,RNA, Viral ,Drug Therapy, Combination ,Female ,business ,Peginterferon alfa-2a ,medicine.drug - Abstract
Patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels have been routinely excluded from large randomized treatment trials; consequently, the efficacy and safety of antiviral therapy in this population are unknown.Patients with at least 3 normal ALT values over an 18-month period were randomized (3:3:1) to treatment with peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks (212 patients), the same combination for 48 weeks (210 patients), or no treatment (69 patients) in a multinational study. All patients were monitored for 72 weeks. The primary measure of efficacy was sustained virologic response (SVR), defined as undetectable serum hepatitis C virus (HCV) RNA by qualitative polymerase chain reaction at the end of 24 weeks of untreated follow-up.No patient cleared HCV RNA in the untreated control group. SVR rates of 30% and 52% were obtained in the 24- and 48-week treatment groups, respectively. In patients infected with HCV genotype 1, SVR rates of 13% and 40% were obtained with 24 and 48 weeks of treatment, respectively (P.0001). In patients infected with genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of treatment, respectively (P = .452). Treatment-related flares in ALT activity were not observed.The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal ALT levels are similar to that in patients with elevated ALT levels. The indication for treatment of hepatitis C can be evaluated independently from baseline ALT activity.
- Published
- 2004
48. Reply: Hepatitis C virus genotype 2/3 patients who can receive an abbreviated course of peginterferon/ribavirin: The important role of initial ribavirin doses
- Author
-
Moisés Diago
- Subjects
chemistry.chemical_compound ,Hepatology ,chemistry ,business.industry ,Ribavirin ,Hepatitis C virus genotype ,Medicine ,PEGINTERFERON/RIBAVIRIN ,business ,Virology - Published
- 2010
49. Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a
- Author
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Vicente Carreño, Solko W. Schalm, Moisés Diago, Friederike Zahm, Félix Manzarbeitia, Irene Vafiadis, Juan Antonio Quiroga, Patrick Marcellin, F. Javier Jiménez, Geoge E. Kitis, Javier Salmerón, and Stephanos J. Hadziyannis
- Subjects
Hepatitis ,Hepatitis B virus ,Piecemeal necrosis ,medicine.medical_specialty ,HBsAg ,Hepatology ,business.industry ,Alpha interferon ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Discontinuation ,HBeAg ,Internal medicine ,Immunology ,medicine ,business ,Interferon alfa ,medicine.drug - Abstract
Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-α) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-α therapy (9 million units [MU] of IFN-α-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-α compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (χ2 = 4.66, P = .031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-α were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3.3%; Fisher's exact test P = .09). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-α retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-α treatment; these were mild and reversible on IFN-α discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-α. Thus, retreatment with IFN-α may be considered a therapeutic option
- Published
- 1999
50. A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis C
- Author
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Mitchell L. Shiffman, U. Hopf, Stefan Zeuzem, Sing Hiem Yap, Francis J. Dudley, Stefan Grüne, Ashok Rakhit, Karen Rittweger, Moisés Diago, Vicente Carreño, Raymond S. Koff, and Howard C. Thomas
- Subjects
medicine.medical_specialty ,Hepatology ,biology ,Bilirubin ,business.industry ,Microgram ,Hepatitis C virus ,Hepatitis C ,medicine.disease_cause ,medicine.disease ,Gastroenterology ,chemistry.chemical_compound ,Pharmacokinetics ,chemistry ,Tolerability ,Alanine transaminase ,Pharmacodynamics ,Internal medicine ,Immunology ,medicine ,biology.protein ,business - Abstract
Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The present open-label, multicenter, dose-escalation phase I/II study was designed to assess tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) in the treatment of chronic hepatitis C. Sixty patients (42 men, 18 women, aged 24-60) were treated with 0.03 microgram/kg (n = 16), 0.1 microgram/kg (n = 14), 0.25 microgram/kg (n = 15), or 0.5 microgram/kg rHuIL-12 (n = 15) for 10 consecutive weeks. rHuIL-12 was generally well tolerated, with 2 patients (3.3%) being withdrawn from treatment for adverse events. Treatment was associated with temporary decreases in neutrophils and lymphocyte counts and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microgram/kg compared with 0.25 microgram/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon gamma (IFN-gamma) were also observed at the highest dose of 0.5 microgram/kg. At the end of treatment hepatitis C virus (HCV) RNA was detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3 of 16 patients of the 0.03-microgram/kg dose group, in 3 of 14 of the 0.10-microgram/kg dose group, in 6 of 15 of the 0.25-microgram/kg dose group, and in 8 of 15 patients of the 0.5-microgram/kg dose group. Although in several cases serum alanine transaminase (ALT) levels decreased either during or after treatment, ALT normalization was observed in only 4 patients at the end of treatment and in 5 patients at the end of follow-up. Significant anti-rHuIL-12 antibody titers were not detectable in any patient. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis C does not appear advantageous in comparison with other currently available treatments.
- Published
- 1999
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