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1. A multisociety Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D, Narro, Graciela E Castro, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart G, Korenjak, Marko, Kowdley, Kris V, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth E, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N, and group, NAFLD Nomenclature consensus

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Digestive Diseases, Clinical Research, Hepatitis, Chronic Liver Disease and Cirrhosis, Substance Misuse, Oral and gastrointestinal, Good Health and Well Being, Female, Male, Humans, Non-alcoholic Fatty Liver Disease, Delphi Technique, Ethanol, Consensus, Hepatomegaly, NAFLD Nomenclature consensus group, ALD, Delphi, MASH, MASLD, Met-ALD, NAFLD, alcohol, metabolic, nomenclature, stigma, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.

Published
2023

2. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

Author

Rinella, Mary, Lazarus, Jeffrey, Ratziu, Vlad, Francque, Sven, Sanyal, Arun, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal, Anstee, Quentin, Arab, Juan, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia, Harrison, Stephen, Kim, Seung, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram, Sookoian, Silvia, Spearman, C, Tiniakos, Dina, Valenti, Luca, Vos, Miriam, Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip, Mitchell-Thain, Robert, Morgan, Timothy, and Loomba, Rohit

Subjects
Male, Female, Humans, Non-alcoholic Fatty Liver Disease, Delphi Technique, Hepatomegaly, Surveys and Questionnaires
Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms nonalcoholic and fatty were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Published
2023

4. acFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study

Author

Feng, Gong, Mózes, Ferenc E., Ji, Dong, Treeprasertsuk, Sombat, Okanoue, Takeshi, Shima, Toshihide, Liang, Huiqing, Tsochatzis, Emmanuel, Chen, Jinjun, Schattenberg, Jörn M., Labenz, Christian, Mahadeva, Sanjiv, Chan, Wah Kheong, Chi, Xiaoling, Delamarre, Adèle, de Lédinghen, Victor, Petta, Salvatore, Bugianesi, Elisabetta, Hagström, Hannes, Boursier, Jérôme, Calleja, José Luis, Goh, George Boon-Bee, Gallego-Durán, Rocio, Sanyal, Arun J., Fan, Jian-Gao, Castéra, Laurent, Lai, Michelle, Harrison, Stephen A., Romero-Gomez, Manuel, Kim, Seung Up, Zhu, Yongfen, Ooi, Geraldine, Shi, Junping, Yoneda, Masato, Nakajima, Atsushi, Zhang, Jing, Lupsor-Platon, Monica, Zhong, Bihui, Cobbold, Jeremy F.L., Ye, Chun-Yan, Eddowes, Peter J., Newsome, Philip, Li, Jie, George, Jacob, He, Fangping, Song, Myeong Jun, Tang, Hong, Fan, Yuchen, Jia, Jidong, Xu, Liang, Lin, Su, Li, Yiling, Lu, Zhonghua, Nan, Yuemin, Niu, Junqi, Yan, Xuebing, Zhou, Yongjian, Liu, Chenghai, Deng, Hong, Ye, Qing, Zeng, Qing-Lei, Li, Lei, Wang, Jing, Yang, Song, Lin, Huapeng, Lee, Hye Won, Yip, Terry Cheuk-Fung, Fournier-Poizat, Céline, Wong, Grace Lai-Hung, Pennisi, Grazia, Armandi, Angelo, Liu, Wen-Yue, Shang, Ying, de Saint-Loup, Marc, Llop, Elba, Teh, Kevin Kim Jun, Lara-Romero, Carmen, Asgharpour, Amon, Mahgoub, Sara, Chan, Mandy Sau-Wai, Canivet, Clemence M., Ji, Fanpu, Xin, Yongning, Chai, Jin, Dong, Zhiyong, Targher, Giovanni, Byrne, Christopher D., He, Na, Mi, Man, Ye, Feng, Wong, Vincent Wai-Sun, Pavlides, Michael, and Zheng, Ming-Hua

Published
2024
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6. A multisociety Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E., Lazarus, Jeffrey V., Ratziu, Vlad, Francque, Sven M., Sanyal, Arun J., Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F., Anstee, Quentin M., Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D., Narro, Graciela E. Castro, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R., Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D., Harrison, Stephen A., Kim, Seung Up, Koot, Bart G., Korenjak, Marko, Kowdley, Kris V., Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R., Powell, Elisabeth E., Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C., Spearman, C. Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B., Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, and Newsome, Philip N.

Published
2024
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7. Validation of the Blood Test MACK-3 for the Noninvasive Diagnosis of Fibrotic Nonalcoholic Steatohepatitis: An International Study With 1924 Patients

Author

Canivet, Clémence M., Zheng, Ming-Hua, Qadri, Sami, Vonghia, Luisa, Chuah, Kee-Huat, Costentin, Charlotte, George, Jacob, Armandi, Angelo, Adams, Leon A., Lange, Naomi F., Blanchet, Odile, Moal, Valérie, Younes, Ramy, Roux, Marine, Chan, Wah-Kheong, Sturm, Nathalie, Eslam, Mohammed, Bugianesi, Elisabetta, Wang, Zhengyi, Dufour, Jean-François, Francque, Sven, Yki-Järvinen, Hannele, Zheng, Kenneth I., and Boursier, Jérôme

Published
2023
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9. Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

Author

Blandin, Alexia, Amosse, Jérémy, Froger, Josy, Hilairet, Grégory, Durcin, Maëva, Fizanne, Lionel, Ghesquière, Valentine, Prieur, Xavier, Chaigneau, Julien, Vergori, Luisa, Dray, Cédric, Pradère, Jean-Philippe, Blandin, Stéphanie, Dupont, Joëlle, Ducluzeau, Pierre-Henri, Dubois, Séverine, Boursier, Jérôme, Cariou, Bertrand, and Le Lay, Soazig

Published
2023
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10. Impact of Type 2 Diabetes on the Accuracy of Noninvasive Tests of Liver Fibrosis With Resulting Clinical Implications

Author

Boursier, Jérôme, Canivet, Clémence M., Costentin, Charlotte, Lannes, Adrien, Delamarre, Adèle, Sturm, Nathalie, Le Bail, Brigitte, Michalak, Sophie, Oberti, Frédéric, Hilleret, Marie-Noelle, Irles-Depé, Marie, Fouchard, Isabelle, Hermabessiere, Paul, Barthelon, Justine, Calès, Paul, Cariou, Bertrand, de Ledinghen, Victor, and Roux, Marine

Published
2023
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11. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Author

Clark, James, Cordell, Heather J., Darlay, Rebecca, Day, Christopher P., Hardy, Tim, Liu, Yang-Lin, Oakley, Fiona, Palmer, Jeremy, Queen, Rachel, Wonders, Kristy, Bossuyt, Patrick M., Holleboom, Adriaan G., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Clement, Karine, Pais, Raluca, Schuppan, Detlef, Allison, Michael, Cuenca, Sergio Rodriguez, Pellegrinelli, Vanessa, Vacca, Michele, Vidal-Puig, Antonio, Hyötyläinen, Tuulia, McGlinchey, Aidan, Orešič, Matej, Sen, Partho, Mato, Jose, Millet, Óscar, Dufour, Jean-Francois, Harrison, Stephen, Neubauer, Stefan, Pavlides, Michael, Mozes, Ferenc, Akhtar, Salma, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Erpicum, Charlotte, Romero-Gomez, Manuel, Gallego-Durán, Rocío, Fernández, Isabel, Karsdal, Morten, Leeming, Diana, Fisker, Mette Juul, Erhardtsen, Elisabeth, Rasmussen, Daniel, Qvist, Per, Sinisi, Antonia, Sandt, Estelle, Tonini, Maria Manuela, Parola, Maurizio, Rosso, Chiara, Marra, Fabio, Gastaldelli, Amalia, Francque, Sven, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Valenti, Luca, Petta, Salvatore, Miele, Luca, Geier, Andreas, Trautwein, Christian, Hockings, Paul, Newsome, Phil, Wenn, David, Pereira Rodrigues, Cecília Maria, Hanf, Rémy, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, Yunis, Carla, Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Kjær, Mette Skalshøi, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Fournier, Céline, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, Twiss, James, Johnson, Katherine, Leary, Peter J., Govaere, Olivier, Barter, Matthew J., Charlton, Sarah H., Cockell, Simon J., Tiniakos, Dina, Zatorska, Michalina, Bedossa, Pierre, Brosnan, M. Julia, Cobbold, Jeremy F., Ekstedt, Mattias, Aithal, Guruprasad P., Clément, Karine, Schattenberg, Jörn M., Boursier, Jerome, Ratziu, Vlad, Bugianesi, Elisabetta, Anstee, Quentin M., and Daly, Ann K.

Published
2022
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12. Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients

Author

Paisant, Anita, Lemoine, Sylvain, Cassinotto, Christophe, de Lédinghen, Victor, Ronot, Maxime, Irlès-Depé, Marie, Vilgrain, Valérie, Le Bail, Brigitte, Paradis, Valérie, Canivet, Clémence M., Michalak, Sophie, Rousselet, Marie-Christine, Rautou, Pierre-Emmanuel, Lebigot, Jérôme, Hunault, Gilles, Crouan, Anne, Aubé, Christophe, and Boursier, Jérôme

Published
2022
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15. Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Author

Petta, Salvatore, Sebastiani, Giada, Viganò, Mauro, Ampuero, Javier, Wai-Sun Wong, Vincent, Boursier, Jerome, Berzigotti, Annalisa, Bugianesi, Elisabetta, Fracanzani, Anna Ludovica, Cammà, Calogero, Enea, Marco, Grottes, Marraud des, Di Marco, Vito, Younes, Ramy, Keyrouz, Aline, Mazzola, Sergio, Mendoza, Yuly, Pennisi, Grazia, Romero-Gomez, Manuel, Craxì, Antonio, and de Ledinghen, Victor

Published
2021
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16. Including Ratio of Platelets to Liver Stiffness Improves Accuracy of Screening for Esophageal Varices That Require Treatment

Author

Huvelin, Sylvie Sacher, Calès, Paul, Valla, Dominique, Bureau, Christophe, Olivier, Anne, Oberti, Frédéric, Boursier, Jérôme, Galmiche, Jean Paul, Vinel, Jean Pierre, Duburque, Clotilde, Attar, Alain, Archambeaud, Isabelle, Benamouzig, Robert, Gaudric, Marianne, Luet, Dominique, Couzigou, Patrice, Planche, Lucie, Coron, Emmanuel, Hiriart, Jean-Baptiste, Chermak, Faiza, Charbonnier, Maude, Nahon, Pierre, Marcellin, Patrick, Guyader, Dominique, Pol, Stanislas, Fontaine, Hélène, Larrey, Dominique, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean-Pierre, Zarski, Jean-Pierre, Leroy, Vincent, Riachi, Ghassan, Péron, Jean-Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean-Frédéric, Abergel, Armand, Serfaty, Lawrence, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, Bacq, Yannick, Wartelle, Claire, Dao, Thông, Benhamou, Yves, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Capron, Dominique, Thiefin, Gérard, Hillaire, Sophie, Di Martino, Vincent, Berger, Arthur, Ravaioli, Federico, Farcau, Oana, Festi, Davide, Stefanescu, Horia, Buisson, François, Ganne-Carriè, Nathalie, Berzigotti, Annalisa, de Ledinghen, Victor, and Petta, Salvatore

Published
2021
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18. Development and Validation of Hepamet Fibrosis Scoring System–A Simple, Noninvasive Test to Identify Patients With Nonalcoholic Fatty Liver Disease With Advanced Fibrosis

Author

Agustin, Salvador, Jorquera, Francisco, Frances, Ruben, Garcia-Samaniego, Javier, Salmeron, Javier, Fernandez-Rodriguez, Conrado, Estevez, Pamela, Andrade, Raul, Soriano, German, Fernandez-Bermejo, Miguel, Arias Loste, María Teresa, Sigüenza, Rebeca, Giannetti, Aurora, del Pozo Maroto, Elvira, Ampuero, Javier, Pais, Raluca, Aller, Rocío, Gallego-Durán, Rocío, Crespo, Javier, García-Monzón, Carmelo, Boursier, Jerome, Vilar, Eduardo, Petta, Salvatore, Zheng, Ming-Hua, Escudero, Desamparados, Calleja, Jose Luis, Aspichueta, Patricia, Diago, Moisés, 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

Published
2020
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19. Criteria to Determine Reliability of Noninvasive Assessment of Liver Fibrosis With Virtual Touch Quantification

Author

Boursier, Jerome, Cassinotto, Christophe, Hunault, Gilles, Shili, Sarah, Lebigot, Jerome, Lapuyade, Bruno, Lannes, Adrien, Hiriart, Jean-Baptiste, Cartier, Victoire, Le Bail, Brigitte, Michalak, Sophie, Mouries, Amaury, Oberti, Frederic, Chermak, Faiza, Fouchard-Hubert, Isabelle, Cales, Paul, Aube, Christophe, and de Ledinghen, Victor

Published
2019
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21. An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Author

Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Sun, Dan-Qin; Targher, Giovanni; Byrne, Christopher D.; Wheeler, David C.; Wong, Vincent Wai-Sun; Fan, Jian-Gao; Tilg, Herbert; Yuan, Wei-Jie; Wanner, Christoph; Gao, Xin; Long, Michelle T.; Nguyen, Mindie H.; Navaneethan, Sankar D.; Yilmaz, Yusuf; Huang, Yuli; Gani, Rino A.; Marzuillo, Pierluigi; Boursier, Jerome; Zhang, Huijie; Jung, Chan-Young; Chai, Jin; Valenti, Luca; Papatheodoridis, George; Musso, Giovanni; Wong, Yu-Jun; El-Kassas, Mohamed; Mendez-Sanchez, Nahum; Sookoian, Silvia; Pavlides, Michael; Duseja, Ajay; Holleboom, Adriaan G.; Shi, Junping; Chan, Wah-Kheong; Fouad, Yasser; Yang, Junwei; Treeprasertsuk, Sombat; Cortez-Pinto, Helena; Hamaguchi, Masahide; Romero-Gomez, Manuel; Al Mahtab, Mamun; Ocama, Ponsiano; Nakajima, Atsushi; Dai, Chunsun; Eslam, Mohammed; Wei, Lai; George, Jacob; Zheng, Ming-Hua, School of Medicine, Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Sun, Dan-Qin; Targher, Giovanni; Byrne, Christopher D.; Wheeler, David C.; Wong, Vincent Wai-Sun; Fan, Jian-Gao; Tilg, Herbert; Yuan, Wei-Jie; Wanner, Christoph; Gao, Xin; Long, Michelle T.; Nguyen, Mindie H.; Navaneethan, Sankar D.; Yilmaz, Yusuf; Huang, Yuli; Gani, Rino A.; Marzuillo, Pierluigi; Boursier, Jerome; Zhang, Huijie; Jung, Chan-Young; Chai, Jin; Valenti, Luca; Papatheodoridis, George; Musso, Giovanni; Wong, Yu-Jun; El-Kassas, Mohamed; Mendez-Sanchez, Nahum; Sookoian, Silvia; Pavlides, Michael; Duseja, Ajay; Holleboom, Adriaan G.; Shi, Junping; Chan, Wah-Kheong; Fouad, Yasser; Yang, Junwei; Treeprasertsuk, Sombat; Cortez-Pinto, Helena; Hamaguchi, Masahide; Romero-Gomez, Manuel; Al Mahtab, Mamun; Ocama, Ponsiano; Nakajima, Atsushi; Dai, Chunsun; Eslam, Mohammed; Wei, Lai; George, Jacob; Zheng, Ming-Hua, and School of Medicine

Abstract

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases., NA

Published
2023

22. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Mozes, Ferenc E., Lee, Jenny A., Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E., Holleboom, Adriaan G., van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jerome, Loup, Marc de Saint, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Lupsor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagstrom, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Vigano, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattias, Nasr, Patrik, Cassinotto, Christophe, de Ledinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P., Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Celine, Geier, Andreas, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M., Harrison, Stephen A., Bossuyt, Patrick M., Pavlides, Michael, Mozes, Ferenc E., Lee, Jenny A., Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E., Holleboom, Adriaan G., van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jerome, Loup, Marc de Saint, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Lupsor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagstrom, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Vigano, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattias, Nasr, Patrik, Cassinotto, Christophe, de Ledinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P., Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Celine, Geier, Andreas, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M., Harrison, Stephen A., Bossuyt, Patrick M., and Pavlides, Michael

Abstract

Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <13 vs 13 to <= 267 vs >267; NFS: <-1455 vs -1455 to <= 0676 vs >0676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was regist, Funding Agencies|Innovative Medicines Initiative 2 (IMI2) Joint Undertaking [777377]; EU; EFPIA; Fonds de Recherche du Quebec-Sante [296306]; Wellcome Trust [221805/Z/20/Z]; Royal Society [221805/Z/20/Z]; KHIDI - Ministry of Health Welfare, Korea [HI14C1135]; Newcastle NIHR Biomedical Research Centre

Published
2023
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23. Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol

Author

Pavlides, Michael, Mozes, Ferenc E., Akhtar, Salma, Wonders, Kristy, Cobbold, Jeremy, Tunnicliffe, Elizabeth M., Allison, Michael, Godfrey, Edmund M., Aithal, Guruprasad P., Francis, Susan, Romero-Gomez, Manuel, Castell, Javier, Fernandez-Lizaranzu, Isabel, Aller, Rocio, Gonzalez, Rebeca Siguenza, Agustin, Salvador, Pericas, Juan M., Boursier, Jerome, Aube, Christophe, Ratziu, Vlad, Wagner, Mathilde, Petta, Salvatore, Antonucci, Michela, Bugianesi, Elisabetta, Faletti, Riccardo, Miele, Luca, Geier, Andreas, Schattenberg, Jorn M., Tilman, Emrich, Ekstedt, Mattias, Lundberg, Peter, Berzigotti, Annalisa, Huber, Adrian T., Papatheodoridis, George, Yki-Jarvinen, Hannele, Porthan, Kimmo, Schneider, Moritz Jorg, Hockings, Paul, Shumbayawonda, Elizabeth, Banerjee, Rajarshi, Pepin, Kay, Kalutkiewicz, Mike, Ehman, Richard L., Coxson, Harvey O., LITMUS Consortium Investigators, Martic, Miljen, Yunis, Carla, Tuthill, Theresa, Bossuyt, Patrick M., Anstee, Quentin M., Neubauer, Stefan, Harrison, Stephen, Pavlides, Michael, Mozes, Ferenc E., Akhtar, Salma, Wonders, Kristy, Cobbold, Jeremy, Tunnicliffe, Elizabeth M., Allison, Michael, Godfrey, Edmund M., Aithal, Guruprasad P., Francis, Susan, Romero-Gomez, Manuel, Castell, Javier, Fernandez-Lizaranzu, Isabel, Aller, Rocio, Gonzalez, Rebeca Siguenza, Agustin, Salvador, Pericas, Juan M., Boursier, Jerome, Aube, Christophe, Ratziu, Vlad, Wagner, Mathilde, Petta, Salvatore, Antonucci, Michela, Bugianesi, Elisabetta, Faletti, Riccardo, Miele, Luca, Geier, Andreas, Schattenberg, Jorn M., Tilman, Emrich, Ekstedt, Mattias, Lundberg, Peter, Berzigotti, Annalisa, Huber, Adrian T., Papatheodoridis, George, Yki-Jarvinen, Hannele, Porthan, Kimmo, Schneider, Moritz Jorg, Hockings, Paul, Shumbayawonda, Elizabeth, Banerjee, Rajarshi, Pepin, Kay, Kalutkiewicz, Mike, Ehman, Richard L., Coxson, Harvey O., LITMUS Consortium Investigators, Martic, Miljen, Yunis, Carla, Tuthill, Theresa, Bossuyt, Patrick M., Anstee, Quentin M., Neubauer, Stefan, and Harrison, Stephen

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721, Funding Agencies|Innovative Medicines Initiative 2 Joint Undertaking [777377]; European Union; EFPIA; Oxford NIHR Biomedical Research Centre; Newcastle NIHR Biomedical Research Centre; NIHR Senior Investigator

Published
2023
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24. A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures

Author

Govaere, Olivier, Hasoon, Megan, Alexander, Leigh, Cockell, Simon, Tiniakos, Dina, Ekstedt, Mattias, Schattenberg, Joern M., Boursier, Jerome, Bugianesi, Elisabetta, Ratziu, Vlad K., Daly, Ann K. M., Anstee, Quentin M., LITMUS Investigators, Govaere, Olivier, Hasoon, Megan, Alexander, Leigh, Cockell, Simon, Tiniakos, Dina, Ekstedt, Mattias, Schattenberg, Joern M., Boursier, Jerome, Bugianesi, Elisabetta, Ratziu, Vlad K., Daly, Ann K. M., Anstee, Quentin M., and LITMUS Investigators

Abstract

Govaere et al. integrate circulating protein data from more than 300 patients with non-alcoholic fatty liver disease (NAFLD) with transcriptomics and develop a non-invasive diagnostics tool to identify patients with at-risk NAFLD based on body mass index, type 2 diabetes status and four circulating proteins. Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic signatures for active steatohepatitis and advanced fibrosis, and correlate these with hepatic transcriptomics to develop a proteo-transcriptomic signature of 31 markers. Deconvolution of this signature by single-cell RNA sequencing reveals the hepatic cell types likely to contribute to proteomic changes with disease progression. As an exemplar of use as a non-invasive diagnostic, logistic regression establishes a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM2), body mass index and type 2 diabetes mellitus status, to identify at-risk steatohepatitis., Funding Agencies|LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) consortium - Innovative Medicines Initiative (IMI2) Program of European Union [777377]; EU Horizon 2020 programme; EFPIA; Elucidating Pathways of Steatohepatitis consortium - Horizon 2020 Framework Program of the European Union [634413]; European NAFLD Registry; Newcastle National Institute for Health and Care Research Biomedical Research Centre

Published
2023
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25. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, Shira Zelber-Sagi, Mary E, R, Jeffrey V, L, Vlad, R, Sven M, F, Arun J, S, Fasiha, K, Diana, R, Manal F, A, Quentin M, A, Juan Pablo, A, Marco, A, Ramon, B, Ulrich, B, Jerome, B, Elisabetta, B, Christopher, B, Graciela E, C, Abhijit, C, Helena, C, Donna, C, Kenneth, C, Mohamed, E, Samuel, K, Wayne, E, Jiangao, F, Samer, G, Cynthia D, G, Stephen A, H, Seung Up, K, Bart, K, Marko, K, Kris, K, Florence, L, Rohit, L, Robert, M, Timothy R, M, Elisabeth, P, Michael, R, Manuel, R, Marcelo, S, Shivaram Prasad, S, Silvia C, S, C Wendy, S, Dina, T, Luca, V, Miriam B, V, Vincent, W, Stavra, X, Yusuf, Y, Zobair, Y, Ansley, H, Marcela, V, Newsome, NVeeral Ajmeral, P, Alazawi, W, Alkhatry, M, Alkhouri, N, Allen, A, Allison, M, Alswat, K, R Alvares-da-Silva, M, Alves-Bezerra, M, J Armstrong, M, Arufe, D, Aschner, P, Baffy, G, Bansal, M, Bedossa, P, Belfort, R, Berg, T, Berzigotti, A, Betel, M, Bianco, C, Brass, C, L Brosgart, C, Matthews Brunt, E, Buti, M, Caldwell, S, Carr, R, Casanovas, T, Castera, L, Caussy, C, Cerda, E, Chalasani, N, Kheong Chan, W, Charatcharoenwitthaya, P, Charlton, M, Cheung, A, Chiodi, D, Chung, R, Cohen, D, Corey, K, P Cotrim, H, Crespo, J, Dassanayake, A, Davidson, N, De Knegt, R, De Ledinghen, V, Demir, M, Diaz, S, Mae Diehl, A, Dimmig, B, Dirchwolf, M, Duseja, A, Dvorak, K, Ekstedt, M, El Wakil, R, Lucía Ferraz, M, Friedman, S, Fuchs, M, Gastaldelli, A, Geerts, A, Geier, A, Girala, M, Goh, G, Goossens, N, Graupera, I, Hagström, H, Henry, Z, Hunyady, B, Hutchison, A, Isaacs, S, Jornayvaz, F, Kemp, C, Kile, D, Kim, W, Kleiner, D, Kohli, R, Kugelmas, M, Lavine, J, Lazo, M, Leite, N, Lozano, A, Luukkonen, P, Macedo, P, Mansour, D, Mantzoros, C, Marchesini, G, Marciano, S, Martinez, K, Vladimirova Mateva, L, M Mato, J, Mccary, A, Miele, L, Mikolasevic, I, Miller, V, Moreno, R, Moylan, C, Nakajima, A, Charles Nault, J, Norris, S, Noureddin, M, P Oliveira, C, Ong, A, Padilla, M, Pais, R, Panduro, A, K Panigrahi, M, Papatheodoridis, G, Pelusi, S, Pérez, M, Perez Escobar, J, Perseghin, G, Pessoa, M, Petta, S, Pinzani, M, Platon Lupsor, M, Rabiee, A, Romeo, S, Rotman, Y, Rowe, I, Salupere, R, Satapathy, S, M Schattenberg, J, Schaufert, W, Schnabl, B, Seim, L, Serfaty, L, Shapiro, D, K Singal, A, Skladany, L, Stefan, N, Stine, J, Sundaram, S, Svegliati-Baroni, G, Szabo, G, Tacke, F, Tanwandee, T, Targher, G, Terrault, N, Tetri, B, Thiele, M, Tisthammer, B, Torre Delgadillo, A, Trauner, M, Tsochatzis, E, Van Kleef, L, Van Mil, S, Vanwagner, L, Antonio Velarde Ruiz Velasco, J, Vesterhus, M, Vilar-Gomez, E, Watt, K, Wattacheril, J, Wilkins, F, Willemse, J, Zekry, A, Zelber-Sagi, S, Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kris, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Philip NVeeral Ajmeral, William Alazawi, Maryam Alkhatry, Naim Alkhouri, Alina Allen, Michael Allison, Khalid Alswat, Mario R Alvares-da-Silva, Michele Alves-Bezerra, Matthew J Armstrong, Diego Arufe, Pablo Aschner, Gyorgy Baffy, Meena Bansal, Pierre Bedossa, Renata Belfort, Thomas Berg, Annalisa Berzigotti, Michael Betel, Cristiana Bianco, Clifford Brass, Carol L Brosgart, Elizabeth Matthews Brunt, Maria Buti, Steve Caldwell, Rotonya Carr, Teresa Casanovas, Laurent Castera, Cyrielle Caussy, Eira Cerda, Naga Chalasani, Wah Kheong Chan, Phunchai Charatcharoenwitthaya, Michael Charlton, Amanda Cheung, Daniela Chiodi, Ray Chung, David Cohen, Kathleen Corey, Helma P Cotrim, Javier Crespo, Anuradha Dassanayake, Nicholas Davidson, Robert De Knegt, Victor De Ledinghen, Münevver Demir, Sebastian Diaz, Anna Mae Diehl, Bruce Dimmig, Melisa Dirchwolf, Ajay Duseja, Karel Dvorak, Mattias Ekstedt, Reda El Wakil, María Lucía Ferraz, Scott Friedman, Michael Fuchs, Amalia Gastaldelli, Anja Geerts, Andreas Geier, Marcos Girala, George Goh, Nicolas Goossens, Isabel Graupera, Hannes Hagström, Zachary Henry, Bela Hunyady, Alan Hutchison, Scott Isaacs, François Jornayvaz, Cynthia Kemp, Denise Kile, Won Kim, David Kleiner, Rohit Kohli, Marcelo Kugelmas, Joel Lavine, Mariana Lazo, Nathalie Leite, Adelina Lozano, Panu Luukkonen, Paula Macedo, Dina Mansour, Christos Mantzoros, Giulio Marchesini, Sebastián Marciano, Kim Martinez, Lyudmila Vladimirova Mateva, Jose M Mato, Alexis McCary, Luca Miele, Ivana Mikolasevic, Veronica Miller, Rosalba Moreno, Cynthia Moylan, Atsushi Nakajima, Jean Charles Nault, Suzanne Norris, Mazen Noureddin, C P Oliveira, Arlin Ong, Martín Padilla, Raluca Pais, Arturo Panduro, Manas K Panigrahi, George Papatheodoridis, Serena Pelusi, Marlene Pérez, Juanita Perez Escobar, Gianluca Perseghin, Mario Pessoa, Salvatore Petta, Massimo Pinzani, Monica Platon Lupsor, Atoosa Rabiee, Stefano Romeo, Yaron Rotman, Ian Rowe, Riina Salupere, Sanjaya Satapathy, Jörn M Schattenberg, Wendy Schaufert, Bernd Schnabl, Lynn Seim, Lawrence Serfaty, David Shapiro, Ashwani K Singal, Lubomir Skladany, Norbert Stefan, Jonathan Stine, Shikha Sundaram, Gianluca Svegliati-Baroni, Gyonzgi Szabo, Frank Tacke, Tawesak Tanwandee, Giovanni Targher, Norah Terrault, Brent Tetri, Maja Thiele, Baron Tisthammer, Aldo Torre Delgadillo, Michael Trauner, Emmanuel Tsochatzis, Laurens Van Kleef, Saskia Van Mil, Lisa VanWagner, Jose Antonio Velarde Ruiz Velasco, Mette Vesterhus, Eduardo Vilar-Gomez, Kymberly Watt, Julia Wattacheril, Fonda Wilkins, José Willemse, Amany Zekry, and Shira Zelber-Sagi

Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmati

Published
2023

26. A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kri, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N, Miele, Luca, NAFLD Nomenclature consensus, Group, Miele, Luca (ORCID:0000-0003-3464-0068), Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher, Castro Narro, Graciela E, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart, Korenjak, Marko, Kowdley, Kri, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wai-Sun Wong, Vincent, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N, Miele, Luca, NAFLD Nomenclature consensus, Group, and Miele, Luca (ORCID:0000-0003-3464-0068)

Abstract

Unlabelled: The principal limitations of the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. Methods: A modified Delphi process was led by three large pan-national liver associations. Consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Results: A total of 236 panellists from 56 countries participated in four online surveys and two hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83% and 78%, respectively. 74% of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms 'non-alcoholic' and 'fatty' were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease (SLD) was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least one of five cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic SLD. A new category, outside pure MASLD, termed MetALD was selected to describe those with MASLD who consume greater amounts of alcohol per week (140 to 350 g/week and 210 to 420 g/week for females and males respectively). Conclusions: The new nomenclature and diagnostic criteria are widely supported, non-stigmatising and can improve awareness and patient identification.

Published
2023

27. Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project) : a comparative diagnostic accuracy study

Author

Vali, Yasaman, Lee, Jenny, Boursier, Jerome, Petta, Salvatore, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Geier, Andreas, Francque, Sven, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-Francois, Leeming, Diana Julie, Harrison, Stephen A, Chen, Yu, Cobbold, Jeremy F, Pavlides, Michael, Holleboom, Adriaan G, Yki-Jarvinen, Hannele, Crespo, Javier, Karsdal, Morten, Ostroff, Rachel, Zafarmand, Mohammad Hadi, Torstenson, Richard, Duffin, Kevin, Yunis, Carla, Brass, Clifford, Ekstedt, Mattias, Aithal, Guruprasad P, Schattenberg, Jörn M, Bugianesi, Elisabetta, Romero-Gomez, Manuel, Ratziu, Vlad, Anstee, Quentin M, Bossuyt, Patrick M, Vali, Yasaman, Lee, Jenny, Boursier, Jerome, Petta, Salvatore, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Geier, Andreas, Francque, Sven, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-Francois, Leeming, Diana Julie, Harrison, Stephen A, Chen, Yu, Cobbold, Jeremy F, Pavlides, Michael, Holleboom, Adriaan G, Yki-Jarvinen, Hannele, Crespo, Javier, Karsdal, Morten, Ostroff, Rachel, Zafarmand, Mohammad Hadi, Torstenson, Richard, Duffin, Kevin, Yunis, Carla, Brass, Clifford, Ekstedt, Mattias, Aithal, Guruprasad P, Schattenberg, Jörn M, Bugianesi, Elisabetta, Romero-Gomez, Manuel, Ratziu, Vlad, Anstee, Quentin M, and Bossuyt, Patrick M

Abstract

Background: The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis—liver biopsy—is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. Methods: This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. Findings: Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinica, Funding: Innovative Medicines Initiative 2 Joint Undertaking

Published
2023
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28. Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study

Author

Lee, Jenny, Westphal, Max, Vali, Yasaman, Boursier, Jerome, Petta, Salvatorre, Ostroff, Rachel, Alexander, Leigh, Chen, Yu, Fournier, Celine, Geier, Andreas, Francque, Sven, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-Francois, Leeming, Diana Julie, Harrison, Stephen, Cobbold, Jeremy, Holleboom, Adriaan G., Yki-Jarvinen, Hannele, Crespo, Javier, Ekstedt, Mattias, Aithal, Guruprasad P., Bugianesi, Elisabetta, Romero-Gomez, Manuel, Torstenson, Richard, Karsdal, Morten, Yunis, Carla, Schattenberg, Joern M., Schuppan, Detlef, Ratziu, Vlad, Brass, Clifford, Duffin, Kevin, Zwinderman, Koos, Pavlides, Michael, Anstee, Quentin M., Bossuyt, Patrick M., LITMUS Investigators, Lee, Jenny, Westphal, Max, Vali, Yasaman, Boursier, Jerome, Petta, Salvatorre, Ostroff, Rachel, Alexander, Leigh, Chen, Yu, Fournier, Celine, Geier, Andreas, Francque, Sven, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-Francois, Leeming, Diana Julie, Harrison, Stephen, Cobbold, Jeremy, Holleboom, Adriaan G., Yki-Jarvinen, Hannele, Crespo, Javier, Ekstedt, Mattias, Aithal, Guruprasad P., Bugianesi, Elisabetta, Romero-Gomez, Manuel, Torstenson, Richard, Karsdal, Morten, Yunis, Carla, Schattenberg, Joern M., Schuppan, Detlef, Ratziu, Vlad, Brass, Clifford, Duffin, Kevin, Zwinderman, Koos, Pavlides, Michael, Anstee, Quentin M., Bossuyt, Patrick M., and LITMUS Investigators

Abstract

Background and Aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F >= 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and Results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS >= 4;53%), at-risk NASH (NASH with F >= 2;35%), significant (F >= 2;47%), and advanced fibrosis (F >= 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis., Funding Agencies|Jenny Lee, Quentin M. Anstee, and Pierre Bedossa conceptualized and designed the study; Jerome Boursier, Salvatore Petta, Kristy Wonders, Dina Tiniakos, Pierre Bedossa, Andreas Geier, Sven Francque, Mike Allison, Georgios Papatheodoridis, Helena Cortez-Pin

Published
2023
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29. An international multidisciplinary consensus statement on MAFLD and the risk of CVD

Author

Zhou, Xiao-Dong, Targher, Giovanni, Byrne, Christopher D., Somers, Virend, Kim, Seung Up, Chahal, C. Anwar A., Wong, Vincent Wai-Sun, Cai, Jingjing, Shapiro, Michael D., Eslam, Mohammed, Steg, Philippe Gabriel, Sung, Ki-Chul, Misra, Anoop, Li, Jian-Jun, Brotons, Carlos, Huang, Yuli, Papatheodoridis, George V., Sun, Aijun, Yilmaz, Yusuf, Chan, Wah-Kheong, Huang, Hui, Méndez-Sánchez, Nahum, Alqahtani, Saleh A., Cortez-Pinto, Helena, Lip, Gregory Y. H., Knegt, Robert J. de, Ocama, Ponsiano, Romero-Gómez, Manuel, Fudim, Marat, Sebastiani, Giada, Son, Jang Won, Ryan, John D., Ikonomidis, Ignatios, Treeprasertsuk, Sombat, Pastori, Daniele, Lupsor-Platon, Monica, Tilg, Herbert, Ghazinyan, Hasmik, Boursier, Jerome, Hamaguchi, Masahide, Nguyen, Mindie H., Fan, Jian-Gao, Goh, George Boon-Bee, Al-Mahtab, Mamun, Hamid, Saeed, Perera, Nilanka, George, Jacob, Zheng, Ming-Hua, Zhou, Xiao-Dong, Targher, Giovanni, Byrne, Christopher D., Somers, Virend, Kim, Seung Up, Chahal, C. Anwar A., Wong, Vincent Wai-Sun, Cai, Jingjing, Shapiro, Michael D., Eslam, Mohammed, Steg, Philippe Gabriel, Sung, Ki-Chul, Misra, Anoop, Li, Jian-Jun, Brotons, Carlos, Huang, Yuli, Papatheodoridis, George V., Sun, Aijun, Yilmaz, Yusuf, Chan, Wah-Kheong, Huang, Hui, Méndez-Sánchez, Nahum, Alqahtani, Saleh A., Cortez-Pinto, Helena, Lip, Gregory Y. H., Knegt, Robert J. de, Ocama, Ponsiano, Romero-Gómez, Manuel, Fudim, Marat, Sebastiani, Giada, Son, Jang Won, Ryan, John D., Ikonomidis, Ignatios, Treeprasertsuk, Sombat, Pastori, Daniele, Lupsor-Platon, Monica, Tilg, Herbert, Ghazinyan, Hasmik, Boursier, Jerome, Hamaguchi, Masahide, Nguyen, Mindie H., Fan, Jian-Gao, Goh, George Boon-Bee, Al-Mahtab, Mamun, Hamid, Saeed, Perera, Nilanka, George, Jacob, and Zheng, Ming-Hua

Abstract

[Background] Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25–30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists., [Methods and results] A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management., [Conculsions] The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

Published
2023

30. Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study

Author

Innovative Medicines Initiative, European Commission, Research Foundation - Flanders, Lee, Jenny, Westphal, Max, Vali, Yasaman, Boursier, Jerome, Petta, Salvatorre, Ostroff, Rachel, Alexander, Leigh, Chen, Yu, Fournier, Celine, Geier, Andreas, Francque, Sven, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-François, Leeming, Diana Julie, Harrison, Stephen, Cobbold, Jeremy, Holleboom, Adriaan G., Yki-Järvinen, Hannele, Crespo, Javier, Ekstedt, Mattias, Aithal, Guruprasad P., Bugianesi, Elisabetta, Romero-Gómez, Manuel, Torstenson, Richard, Karsdal, Morten, Yunis, Carla27, Schattenberg, Jörn M., Schuppan, Detlef, Ratziu, Vlad, Brass, Clifford, Duffin, Kevin, Zwinderman, Koos, Pavlides, Michael, Anstee, Quentin M., Bossuyt, Patrick M., LITMUS investigators, Innovative Medicines Initiative, European Commission, Research Foundation - Flanders, Lee, Jenny, Westphal, Max, Vali, Yasaman, Boursier, Jerome, Petta, Salvatorre, Ostroff, Rachel, Alexander, Leigh, Chen, Yu, Fournier, Celine, Geier, Andreas, Francque, Sven, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-François, Leeming, Diana Julie, Harrison, Stephen, Cobbold, Jeremy, Holleboom, Adriaan G., Yki-Järvinen, Hannele, Crespo, Javier, Ekstedt, Mattias, Aithal, Guruprasad P., Bugianesi, Elisabetta, Romero-Gómez, Manuel, Torstenson, Richard, Karsdal, Morten, Yunis, Carla27, Schattenberg, Jörn M., Schuppan, Detlef, Ratziu, Vlad, Brass, Clifford, Duffin, Kevin, Zwinderman, Koos, Pavlides, Michael, Anstee, Quentin M., Bossuyt, Patrick M., and LITMUS investigators

Abstract

[Background and Aims] Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD., [Approach and Results] Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models. Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82)., [Conclusions] Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.

Published
2023

31. Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study

Author

Innovative Medicines Initiative, European Commission, Vali, Yasaman, Lee, Jenny, Boursier, Jerome, Petta, Salvatore, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Geier, Andreas, Francque, Sven, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-François, Leeming, Diana Julie, Harrison, Stephen A., Chen, Yu, Cobbold, Jeremy F., Pavlides, Michael, Holleboom, Adriaan G., Yki-Jarvinen, Hannele, Crespo, Javier, Karsdal, Morten, Ostroff, Rachel, Zafarmand, Mohammad Hadi, Torstenson, Richard, Duffin, Kevin, Yunis, Carla, Brass, Clifford, Ekstedt, Mattias, Aithal, Guruprasad P., Schattenberg, Jörn M., Bugianesi, Elisabetta, Romero-Gómez, Manuel, Ratziu, Vlad, Anstee, Quentin M., Bossuyt, Patrick M., on behalf of theLiver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium investigators, Innovative Medicines Initiative, European Commission, Vali, Yasaman, Lee, Jenny, Boursier, Jerome, Petta, Salvatore, Wonders, Kristy, Tiniakos, Dina, Bedossa, Pierre, Geier, Andreas, Francque, Sven, Allison, Mike, Papatheodoridis, Georgios, Cortez-Pinto, Helena, Pais, Raluca, Dufour, Jean-François, Leeming, Diana Julie, Harrison, Stephen A., Chen, Yu, Cobbold, Jeremy F., Pavlides, Michael, Holleboom, Adriaan G., Yki-Jarvinen, Hannele, Crespo, Javier, Karsdal, Morten, Ostroff, Rachel, Zafarmand, Mohammad Hadi, Torstenson, Richard, Duffin, Kevin, Yunis, Carla, Brass, Clifford, Ekstedt, Mattias, Aithal, Guruprasad P., Schattenberg, Jörn M., Bugianesi, Elisabetta, Romero-Gómez, Manuel, Ratziu, Vlad, Anstee, Quentin M., Bossuyt, Patrick M., and on behalf of theLiver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium investigators

Abstract

[Background] The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis—liver biopsy—is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment., [Methods] This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials., [Findings] Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54–0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75–0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86–0·94]), ADAPT (0·85 [0·81–0·89]), and FibroScan liver stiffness measurement (0·83 [0·80–0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4–5]), then ADAPT (six [5–7]), MACK-3 (seven [6–8]), and PRO-C3 (nine [7–11])., [Interpretation] None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort.

Published
2023

32. A multisociety Delphi consensus statement on new fatty liver disease nomenclature

Author

Rinella, Mary E., Lazarus, Jeffrey V., Ratziu, Vlad, Francque, Sven M., Sanyal, Arun J., Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal, Anstee, Quentin, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramón, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D., Castro Narro, Graciela E., Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R., Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D., Harrison, Stephen A., Kim, Seung Up, Koot, Bart G., Korenjak, Marko, Kowdley, Kris V., Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R., Powell, Elisabeth E., Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C., Spearman, C. Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B., Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N., on behalf of the NAFLD Nomenclature consensus group, Rinella, Mary E., Lazarus, Jeffrey V., Ratziu, Vlad, Francque, Sven M., Sanyal, Arun J., Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal, Anstee, Quentin, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramón, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D., Castro Narro, Graciela E., Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R., Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D., Harrison, Stephen A., Kim, Seung Up, Koot, Bart G., Korenjak, Marko, Kowdley, Kris V., Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R., Powell, Elisabeth E., Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C., Spearman, C. Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B., Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N., and on behalf of the NAFLD Nomenclature consensus group

Abstract

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and c

Published
2023

33. Association Between Severity of Obstructive Sleep Apnea and Blood Markers of Liver Injury

Author

Person, Christine, Molinier, Olivier, Paris, Audrey, Caby, Isabelle, Bellier, Maël, Langelot-Richard, Marie, Leclair-Visonneau, Laurence, Jaffre, Sandrine, Corne, Frédéric, de la Tranchade, Marc Normand, Rouault, Béatrice, Racineux, Jean-Louis, Gosselin, Christelle, Pelletier-Fleury, Nathalie, Trzepizur, Wojciech, Boursier, Jérôme, Mansour, Yasmina, Le Vaillant, Marc, Chollet, Sylvaine, Pigeanne, Thierry, Bizieux-Thaminy, Acya, Humeau, Marie-Pierre, Alizon, Claire, Goupil, François, Meslier, Nicole, Priou, Pascaline, Calès, Paul, and Gagnadoux, Frédéric

Published
2016
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35. Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study

Author

Zhang, Huai, primary, Rios, Rafael S., additional, Boursier, Jerome, additional, Anty, Rodolphe, additional, Chan, Wah-Kheong, additional, George, Jacob, additional, Yilmaz, Yusuf, additional, Wong, Vincent Wai-Sun, additional, Fan, Jiangao, additional, Dufour, Jean-François, additional, Papatheodoridis, George, additional, Chen, Li, additional, Schattenberg, Jörn M., additional, Shi, Junping, additional, Xu, Liang, additional, Wong, Grace Lai-Hung, additional, Lange, Naomi F., additional, Papatheodoridi, Margarita, additional, Mi, Yuqiang, additional, Zhou, Yujie, additional, Byrne, Christopher D., additional, Targher, Giovanni, additional, Feng, Gong, additional, and Zheng, Minghua, additional

Published
2023
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36. Reply

Author

Roux, Marine, primary and Boursier, Jerome, additional

Published
2023
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37. Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study

Author

Zhang, Huai, Rios, Rafael S, Boursier, Jerome, Anty, Rodolphe, Chan, Wah-Kheong, George, Jacob, Yilmaz, Yusuf, Wong, Vincent Wai-Sun, Fan, Jiangao, Dufour, Jean-François, Papatheodoridis, George, Chen, Li, Schattenberg, Jörn M, Shi, Junping, Liang, Xu, Wong, Grace Lai-Hung, Lange, Naomi F, Papatheodoridi, Margarita, Yuqiang, Mi, Zhou, Yujie, Byrne, Christopher D, Targher, Giovanni, Feng, Gong, and Zheng, Minghua

Subjects
Diagnosis, Apoptosis, 610 Medicine & health, General Medicine, Cytokeratin-18, 610 Medizin und Gesundheit, Liver histology, Non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease
Abstract

BACKGROUND Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 including a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension (P

Published
2023

40. Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests.

Author

Boursier, Jérôme, Roux, Marine, Costentin, Charlotte, Chaigneau, Julien, Fournier-Poizat, Céline, Trylesinski, Aldo, Canivet, Clémence M., Michalak, Sophie, Le Bail, Brigitte, Paradis, Valérie, Bedossa, Pierre, Sturm, Nathalie, de Ledinghen, Victor, AFEF group for the study of liver fibrosis, Barthelon, Justine, Boursier, Jerome, Cales, Paul, Canivet, Clémence, Decaens, Thomas, and Delamarre, Adèle

Subjects
NON-alcoholic fatty liver disease, HEPATIC fibrosis, CIRRHOSIS of the liver, LIVER biopsy
Abstract

Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only −2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD. The practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD are not well defined. Here, the authors develop and validate two diagnostic tools: a stepwise stratification algorithm including a cirrhosis group, and a risk prediction chart providing a personalized assessment of the individual probability of cirrhosis. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression : Diagnostic and mechanistic relevance

Author

Johnson, Katherine, Leary, Peter J., Govaere, Olivier, Barter, Matthew J., Charlton, Sarah H., Cockell, Simon J., Tiniakos, Dina, Zatorska, Michalina, Bedossa, Pierre, Brosnan, M. Julia, Cobbold, Jeremy F., Ekstedt, Mattias, Aithal, Guruprasad P., Clement, Karine, Schattenberg, Joern M., Boursier, Jerome, Ratziu, Vlad, Bugianesi, Elisabetta, Anstee, Quentin M., Daly, Ann K., Johnson, Katherine, Leary, Peter J., Govaere, Olivier, Barter, Matthew J., Charlton, Sarah H., Cockell, Simon J., Tiniakos, Dina, Zatorska, Michalina, Bedossa, Pierre, Brosnan, M. Julia, Cobbold, Jeremy F., Ekstedt, Mattias, Aithal, Guruprasad P., Clement, Karine, Schattenberg, Joern M., Boursier, Jerome, Ratziu, Vlad, Bugianesi, Elisabetta, Anstee, Quentin M., and Daly, Ann K.

Abstract

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2-4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5-8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2-4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. La, Funding Agencies|Innovative Medicines Initiative (IMI2) Program of the European Union [777377]; European Unions Horizon 2020 research and innovation programme; EFPIA; Newcastle NIHR Biomedical Research Centre; European NAFLD Registry

Published
2022
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42. Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events

Author

Intercept Pharmaceuticals, Ekstedt, Mattias [0000-0002-5590-8601], Bonacci, Martin [0000-0002-4528-8066], Cure, Sandrine [0000-0002-8296-0771], Kechagias, Stergios [0000-0001-7614-739X], Boursier, Jerome, Hagström, Hannes, Ekstedt, Mattias, Moreau, Clemence, Bonacci, Martin, Cure, Sandrine, Ampuero, Javier, Nasr, Patrik, Tallab, Lilian, Canivet, Clémence M., Kechagias, Stergios, Sánchez-Torrijos, Yolanda, Dincuff, Eloise, Lucena-Valera, Ana, Roux, Marine, Riou, Jeremie, Trylesinski, Aldo, Romero-Gómez, Manuel, Intercept Pharmaceuticals, Ekstedt, Mattias [0000-0002-5590-8601], Bonacci, Martin [0000-0002-4528-8066], Cure, Sandrine [0000-0002-8296-0771], Kechagias, Stergios [0000-0001-7614-739X], Boursier, Jerome, Hagström, Hannes, Ekstedt, Mattias, Moreau, Clemence, Bonacci, Martin, Cure, Sandrine, Ampuero, Javier, Nasr, Patrik, Tallab, Lilian, Canivet, Clémence M., Kechagias, Stergios, Sánchez-Torrijos, Yolanda, Dincuff, Eloise, Lucena-Valera, Ana, Roux, Marine, Riou, Jeremie, Trylesinski, Aldo, and Romero-Gómez, Manuel

Abstract

[Background & Aims] Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD., [Methods] A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrell’s C-index., [Results] FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrell’s C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrell’s C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with “FIB4 <1.30”, those with “FIB4 ≥1.30 then VCTE <8.0 kPa” had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3–6.8), whereas the risk of LREs significantly increased in patients with “FIB4 ≥1.30 then VCTE 8.0-12.0 kPa” (aHR 3.8; 95% CI 1.3–10.9), and even more for those with “FIB4 ≥1.30 then VCTE >12.0 kPa” (aHR 12.4; 95% CI 5.1–30.2)., [Conclusion] VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management.

Published
2022

43. Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events

Author

Boursier, Jerome, Hagstrom, Hannes, Ekstedt, Mattias, Moreau, Clemence, Bonacci, Martin, Cure, Sandrine, Ampuero, Javier, Nasr, Patrik, Tallab, Lilian, Canivet, Clemence M., Kechagias, Stergios, Sanchez, Yolanda, Dincuff, Eloise, Lucena, Ana, Roux, Marine, Riou, Jeremie, Trylesinski, Aldo, Romero-Gomez, Manuel, Boursier, Jerome, Hagstrom, Hannes, Ekstedt, Mattias, Moreau, Clemence, Bonacci, Martin, Cure, Sandrine, Ampuero, Javier, Nasr, Patrik, Tallab, Lilian, Canivet, Clemence M., Kechagias, Stergios, Sanchez, Yolanda, Dincuff, Eloise, Lucena, Ana, Roux, Marine, Riou, Jeremie, Trylesinski, Aldo, and Romero-Gomez, Manuel

Abstract

Background & Aims: Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. Methods: A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrells C-index. Results: FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrells C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrells C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 >- 1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3-6.8), whereas the risk of LREs significantly increased in patients with "FIB4 >1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3-10.9), and even more for those with "FIB4 >-1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1- 30.2). Conclusion: VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of, Funding Agencies|Intercept Pharmaceuticals

Published
2022
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44. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Author

Johnson, Katherine, primary, Leary, Peter J., additional, Govaere, Olivier, additional, Barter, Matthew J., additional, Charlton, Sarah H., additional, Cockell, Simon J., additional, Tiniakos, Dina, additional, Zatorska, Michalina, additional, Bedossa, Pierre, additional, Brosnan, M. Julia, additional, Cobbold, Jeremy F., additional, Ekstedt, Mattias, additional, Aithal, Guruprasad P., additional, Clément, Karine, additional, Schattenberg, Jörn M., additional, Boursier, Jerome, additional, Ratziu, Vlad, additional, Bugianesi, Elisabetta, additional, Anstee, Quentin M., additional, Daly, Ann K., additional, Clark, James, additional, Cordell, Heather J., additional, Darlay, Rebecca, additional, Day, Christopher P., additional, Hardy, Tim, additional, Liu, Yang-Lin, additional, Oakley, Fiona, additional, Palmer, Jeremy, additional, Queen, Rachel, additional, Wonders, Kristy, additional, Bossuyt, Patrick M., additional, Holleboom, Adriaan G., additional, Zafarmand, Hadi, additional, Vali, Yasaman, additional, Lee, Jenny, additional, Clement, Karine, additional, Pais, Raluca, additional, Schuppan, Detlef, additional, Allison, Michael, additional, Cuenca, Sergio Rodriguez, additional, Pellegrinelli, Vanessa, additional, Vacca, Michele, additional, Vidal-Puig, Antonio, additional, Hyötyläinen, Tuulia, additional, McGlinchey, Aidan, additional, Orešič, Matej, additional, Sen, Partho, additional, Mato, Jose, additional, Millet, Óscar, additional, Dufour, Jean-Francois, additional, Harrison, Stephen, additional, Neubauer, Stefan, additional, Pavlides, Michael, additional, Mozes, Ferenc, additional, Akhtar, Salma, additional, Banerjee, Rajarshi, additional, Kelly, Matt, additional, Shumbayawonda, Elizabeth, additional, Dennis, Andrea, additional, Erpicum, Charlotte, additional, Romero-Gomez, Manuel, additional, Gallego-Durán, Rocío, additional, Fernández, Isabel, additional, Karsdal, Morten, additional, Leeming, Diana, additional, Fisker, Mette Juul, additional, Erhardtsen, Elisabeth, additional, Rasmussen, Daniel, additional, Qvist, Per, additional, Sinisi, Antonia, additional, Sandt, Estelle, additional, Tonini, Maria Manuela, additional, Parola, Maurizio, additional, Rosso, Chiara, additional, Marra, Fabio, additional, Gastaldelli, Amalia, additional, Francque, Sven, additional, Kechagias, Stergios, additional, Yki-Järvinen, Hannele, additional, Porthan, Kimmo, additional, van Mil, Saskia, additional, Papatheodoridis, George, additional, Cortez-Pinto, Helena, additional, Valenti, Luca, additional, Petta, Salvatore, additional, Miele, Luca, additional, Geier, Andreas, additional, Trautwein, Christian, additional, Hockings, Paul, additional, Newsome, Phil, additional, Wenn, David, additional, Pereira Rodrigues, Cecília Maria, additional, Hanf, Rémy, additional, Chaumat, Pierre, additional, Rosenquist, Christian, additional, Trylesinski, Aldo, additional, Ortiz, Pablo, additional, Duffin, Kevin, additional, Yunis, Carla, additional, Miller, Melissa, additional, Tuthill, Theresa, additional, Ertle, Judith, additional, Younes, Ramy, additional, Alexander, Leigh, additional, Ostroff, Rachel, additional, Kjær, Mette Skalshøi, additional, Mikkelsen, Lars Friis, additional, Brass, Clifford, additional, Jennings, Lori, additional, Balp, Maria-Magdalena, additional, Martic, Miljen, additional, Hanauer, Guido, additional, Shankar, Sudha, additional, Torstenson, Richard, additional, Fournier, Céline, additional, Ehman, Richard, additional, Kalutkiewicz, Michael, additional, Pepin, Kay, additional, Myers, Joel, additional, Shevell, Diane, additional, Ho, Gideon, additional, Landgren, Henrik, additional, Myers, Rob, additional, Doward, Lynda, additional, Whalley, Diane, additional, and Twiss, James, additional

Published
2022
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45. Liver‐related and extrahepatic events in patients with non‐alcoholic fatty liver disease: a retrospective competing risks analysis

Author

Pennisi, Grazia, primary, Enea, Marco, additional, Romero‐Gomez, Manuel, additional, Viganò, Mauro, additional, Bugianesi, Elisabetta, additional, Wong, Vincent W.‐S., additional, Fracanzani, Anna Ludovica, additional, Sebastiani, Giada, additional, Boursier, Jerome, additional, Berzigotti, Annalisa, additional, Eslam, Mohammed, additional, Ampuero, Javier, additional, Benmassaoud, Amine, additional, La Mantia, Claudia, additional, Mendoza, Yuly P., additional, George, Jacob, additional, Craxì, Antonio, additional, Camma', Calogero, additional, de Ledinghen, Victor, additional, and Petta, Salvatore, additional

Published
2022
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46. Cross-linkage between bacterial taxonomy and gene functions: a study of metagenome-assembled genomes of Gut Microbiota in adult non-alcoholic fatty liver disease

Author

Canivet, Clemence, David, Norma, Pailhoriès, Helene, Briand, Martial, Guy, Cynthia, Bouchez, Olivier, Hunault, Gilles, Fizanne, Lionel, Lannes, Adrien, Oberti, Frederic, Fouchard, Isabelle, Calès, Paul, Diehl, Anna Mae, Barret, Matthieu, Boursier, Jerome, Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Duke University Medical Center, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Angers University Hospital, Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université Toulouse III - Paul Sabatier (UT3)

Subjects
nutritional and metabolic diseases, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, digestive system, digestive system diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background The reconstruction of metagenome-assembled genomes (MAGs) has emerged as a powerful approach for combining the taxonomic and functional content of microbial populations.Aim To use this new approach to highlight mechanisms linking gut microbiota to NAFLD severityMethods Stool samples were collected from 96 NAFLD patients on the day of liver biopsy. Shotgun DNA sequencing of the gut microbiota was performed on an Illumina HiSeq3000 system. Contigs were binned into MAGs according to their co-abundances and tetranucleotide frequencies using Metabat v.0.32.4. Predicted protein-coding genes were clustered in orthologous groups (OGs) with DIAMOND against the EggNOG v4.5 database. Liver biopsies were read in accordance with the NASH CRN classification.Results Fifty-four patients had NASH and 44 had significant fibrosis (F >= 2). Sequencing of DNA extracted from stools resulted in 13.8 + 3.2 million paired-end reads per sample. Of the 4,000 reconstructed MAGs, 220 in NASH patients, 192 in non-NASH patients, 203 in F >= 2 patients and 230 in F0-1 patients had > 70% completeness and < 5% contamination. Within these MAGs, 28 OGs were associated with NASH, 33 with significant fibrosis, and seven with both NASH and significant fibrosis. The study of MAGs showed associations between NAFLD severity and some gut bacteria with microbiota functions related to hydrogen sulfide production, citrate transport, hemicellulose degradation, aldehyde production and vitamin B12 synthesis.Conclusion Using new metagenomics methods, our study unveils potential mechanisms by which certain bacteria from the gut microbiota could protect or contribute to the development of NASH and liver fibrosis in NAFLD.

Published
2021

47. enDiagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Author

Mózes, Ferenc Emil, Lee, Jenny A, Selvaraj, Emmanuel Anandraj, Jayaswal, Arjun Narayan Ajmer, Trauner, Michael, Boursier, Jerome, Fournier, Céline, Staufer, Katharina, Stauber, Rudolf E, Bugianesi, Elisabetta, Younes, Ramy, Gaia, Silvia, Lupșor-Platon, Monica, Petta, Salvatore, Shima, Toshihide, Okanoue, Takeshi, Mahadeva, Sanjiv, Chan, Wah-Kheong, Eddowes, Peter J, Hirschfield, Gideon M, Newsome, Philip Noel, Wong, Vincent Wai-Sun, de Ledinghen, Victor, Fan, Jiangao, Shen, Feng, Cobbold, Jeremy F, Sumida, Yoshio, Okajima, Akira, Schattenberg, Jörn M, Labenz, Christian, Kim, Won, Lee, Myoung Seok, Wiegand, Johannes, Karlas, Thomas, Yılmaz, Yusuf, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Cassinotto, Christophe, Aggarwal, Sandeep, Garg, Harshit, Ooi, Geraldine J, Nakajima, Atsushi, Yoneda, Masato, Ziol, Marianne, Barget, Nathalie, Geier, Andreas, Tuthill, Theresa, Brosnan, M Julia, Anstee, Quentin Mark, Neubauer, Stefan, Harrison, Stephen A, Bossuyt, Patrick M, and Pavlides, Michael

Subjects
610 Medicine & health
Abstract

OBJECTIVE Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. DESIGN Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. RESULTS Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (

Published
2021

48. acNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study

Author

National Natural Science Foundation of China, Public Health Department of Zhejiang Province, Wu, Xi-Xi, Zheng, Kenneth I., Boursier, Jerome, Chan, Wah-Kheong, Yilmaz, Yusuf, Romero-Gómez, Manuel, El Kassas, Mohamed, Targher, Giovanni, Byrne, Christopher D., Huang, Zhi-Ming, Zheng, Ming-Hua, National Natural Science Foundation of China, Public Health Department of Zhejiang Province, Wu, Xi-Xi, Zheng, Kenneth I., Boursier, Jerome, Chan, Wah-Kheong, Yilmaz, Yusuf, Romero-Gómez, Manuel, El Kassas, Mohamed, Targher, Giovanni, Byrne, Christopher D., Huang, Zhi-Ming, and Zheng, Ming-Hua

Abstract

[Background] There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD)., [Methods] We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1,089)., [Findings] The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1,089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels., [Interpretation] The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries.

Published
2021

49. Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Author

Fonds de Recherche du Québec, McGill University, Petta, Salvatore, Sebastiani, Giada, Viganò, Mauro, Ampuero, Javier, Wai-Sun Wong, Vincent, Boursier, Jerome, Berzigotti, Annalisa, Bugianesi, Elisabetta, Fracanzani, Anna Ludovica, Cammà, Calogero, Enea, Marco, des Grottes, Marraud, Di Marco, Vito, Younes, Ramy, Keyrouz, Aline, Mazzola, Sergio, Mendoza, Yuly, Pennisi, Grazia, Romero-Gómez, Manuel, Craxi, Antonio, de Ledinghen, Victor, Fonds de Recherche du Québec, McGill University, Petta, Salvatore, Sebastiani, Giada, Viganò, Mauro, Ampuero, Javier, Wai-Sun Wong, Vincent, Boursier, Jerome, Berzigotti, Annalisa, Bugianesi, Elisabetta, Fracanzani, Anna Ludovica, Cammà, Calogero, Enea, Marco, des Grottes, Marraud, Di Marco, Vito, Younes, Ramy, Keyrouz, Aline, Mazzola, Sergio, Mendoza, Yuly, Pennisi, Grazia, Romero-Gómez, Manuel, Craxi, Antonio, and de Ledinghen, Victor

Abstract

[Background & Aims] Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events., [Methods] We performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months)., [Results] Based on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02)., [Conclusions] In patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.

Published
2021

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