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1. A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease

Author

Zhang, Huai, Targher, Giovanni, Byrne, Christopher D., Kim, Seung Up, Wong, Vincent Wai-Sun, Valenti, Luca, Glickman, Myer, Ponce, Jaime, Mantzoros, Christos S., Crespo, Javier, Gronbaek, Henning, Yang, Wah, Eslam, Mohammed, Wong, Robert J., Machado, Mariana Verdelho, Yu, Ming-Lung, Ghanem, Omar M., Okanoue, Takeshi, Liu, Jun-Feng, Lee, Yong-ho, Xu, Xiao-Yuan, Pan, Qiuwei, Sui, Meili, Lonardo, Amedeo, Yilmaz, Yusuf, Zhu, Li-Yong, Moreno, Christophe, Miele, Luca, Lupsor-Platon, Monica, Zhao, Lei, LaMasters, Teresa LeAnn, Gish, Robert G., Zhang, Huijie, Nedelcu, Marius, Chan, Wah Kheong, Xia, Ming-Feng, Bril, Fernando, Shi, Jun-Ping, Datz, Christian, Romeo, Stefano, Sun, Jian, Liu, Dan, Sookoian, Silvia, Mao, Yi-Min, Méndez-Sánchez, Nahum, Wang, Xiao-Yan, Pyrsopoulos, Nikolaos T., Fan, Jian-Gao, Fouad, Yasser, Sun, Dan-Qin, Giannini, Cosimo, Chai, Jin, Xia, Ze-Feng, Jun, Dae Won, Li, Guo-Jing, Treeprasertsuk, Sombat, Li, Ying-Xu, Cheung, Tan To, Zhang, Faming, Goh, George Boon-Bee, Furuhashi, Masato, Seto, Wai-Kay, Huang, Hui, Di Sessa, Anna, Li, Qing-Hong, Cholongitas, Evangelos, Zhang, Le, Silveira, Themis Reverbel, Sebastiani, Giada, Adams, Leon A., Chen, Wei, Qi, Xiaolong, Rankovic, Ivan, De Ledinghen, Victor, Lv, Wen-Jie, Hamaguchi, Masahide, Kassir, Radwan, Müller-Wieland, Dirk, Romero-Gomez, Manuel, Xu, Ying, Xu, Yi-Cong, Chen, Shi-Yao, Kermansaravi, Mohammad, Kuchay, Mohammad Shafi, Lefere, Sander, Parmar, Chetan, Lip, Gregory Y. H., Liu, Chun-Jen, Åberg, Fredrik, Lau, George, George, Jacob, Sarin, Shiv Kumar, Zhou, Jing-Ya, and Zheng, Ming-Hua

Published
2024
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4. Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Author

Lazarus, Jeffrey V, Castera, Laurent, Mark, Henry E, Allen, Alina M, Adams, Leon A, Anstee, Quentin M, Arrese, Marco, Alqahtani, Saleh A, Bugianesi, Elisabetta, Colombo, Massimo, Cusi, Kenneth, Hagström, Hannes, Loomba, Rohit, Romero-Gómez, Manuel, Schattenberg, Jörn M, Thiele, Maja, Valenti, Luca, Wong, Vincent Wai-Sun, Yilmaz, Yusuf, Younossi, Zobair M, Francque, Sven M, and Tsochatzis, Emmanuel A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Chronic Liver Disease and Cirrhosis, Liver Disease, Digestive Diseases, Good Health and Well Being, Hepatology, NAFLD, NITs, FIB-4, Elastography, NFS, FIB-4, Fibrosis-4, NAFLD, Non-alcoholic fatty liver disease, NFS, NAFLD fibrosis score, NIT, Non-invasive test, Clinical sciences
Abstract

Background & aimsNon-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings.MethodsA survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas.ResultsThere were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of 7.5 to >20 kPa, respectively).ConclusionsThe cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management.Lay summaryOwing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

Published
2023

6. Author Correction: Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author

Valenti, Luca, Corradini, Elena, Adams, Leon A., Aigner, Elmar, Alqahtani, Saleh, Arrese, Marco, Bardou-Jacquet, Edouard, Bugianesi, Elisabetta, Fernandez-Real, Jose-Manuel, Girelli, Domenico, Hagström, Hannes, Henninger, Benjamin, Kowdley, Kris, Ligabue, Guido, McClain, Donald, Lainé, Fabrice, Miyanishi, Koji, Muckenthaler, Martina U., Pagani, Alessia, Pedrotti, Patrizia, Pietrangelo, Antonello, Prati, Daniele, Ryan, John D., Silvestri, Laura, Spearman, C. Wendy, Stål, Per, Tsochatzis, Emmanuel A., Vinchi, Francesca, Zheng, Ming-Hua, and Zoller, Heinz

Published
2024
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8. Global burden of metabolic diseases, 1990–2021

Author

Zhang, Huai, Zhou, Xiao-Dong, Shapiro, Michael D., Lip, Gregory Y.H., Tilg, Herbert, Valenti, Luca, Somers, Virend K., Byrne, Christopher D., Targher, Giovanni, Yang, Wah, Viveiros, Octavio, Opio, Christopher Kenneth, Mantzoros, Christos S., Ryan, John D., Kok, Kenneth Yuh Yen, Jumaev, Nozim Adxamovich, Perera, Nilanka, Robertson, Andrew Gerard, Abu-Abeid, Adam, Misra, Anoop, Wong, Yu Jun, Ruiz-Úcar, Elena, Ospanov, Oral, Kızılkaya, Mehmet Celal, Luo, Fei, Méndez-Sánchez, Nahum, Zuluaga, Mauricio, Lonardo, Amedeo, Al Momani, Hazem, Toro-Huamanchumo, Carlos Jesus, Adams, Leon, Al-Busafi, Said A., Sharara, Ala I., Chan, Wah-Kheong, Abbas, Syed Imran, Sookoian, Silvia, Treeprasertsuk, Sombat, Ocama, Ponsiano, Alswat, Khalid, Kong, Alice Pik-Shan, Ataya, Karim, Lim-Loo, Michelle Ching, Oviedo, Rodolfo J., Szepietowski, Olivia, Fouad, Yasser, Zhang, Huijie, Abdelbaki, Tamer N., Katsouras, Christos S., Prasad, Arun, Thaher, Omar, Ali, Arshad, Molina, Gabriel Alejandro, Sung, Ki-Chul, Chen, Qin-Fen, Lesmana, Cosmas Rinaldi Adithya, and Zheng, Ming-Hua

Published
2024
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9. Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author

Valenti, Luca, Corradini, Elena, Adams, Leon A., Aigner, Elmar, Alqahtani, Saleh, Arrese, Marco, Bardou-Jacquet, Edouard, Bugianesi, Elisabetta, Fernandez-Real, Jose-Manuel, Girelli, Domenico, Hagström, Hannes, Henninger, Benjamin, Kowdley, Kris, Ligabue, Guido, McClain, Donald, Lainé, Fabrice, Miyanishi, Koji, Muckenthaler, Martina U., Pagani, Alessia, Pedrotti, Patrizia, Pietrangelo, Antonello, Prati, Daniele, Ryan, John D., Silvestri, Laura, Spearman, C. Wendy, Stål, Per, Tsochatzis, Emmanuel A., Vinchi, Francesca, Zheng, Ming-Hua, and Zoller, Heinz

Published
2023
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11. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease

Author

Kanwal, Fasiha, Shubrook, Jay H, Adams, Leon A, Pfotenhauer, Kim, Wai-Sun Wong, Vincent, Wright, Eugene, Abdelmalek, Manal F, Harrison, Stephen A, Loomba, Rohit, Mantzoros, Christos S, Bugianesi, Elisabetta, Eckel, Robert H, Kaplan, Lee M, El-Serag, Hashem B, and Cusi, Kenneth

Subjects
Health Services, Clinical Research, Hepatitis, Liver Disease, Prevention, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Oral and gastrointestinal, Good Health and Well Being, Clinical Decision-Making, Consensus, Critical Pathways, Decision Support Techniques, Evidence-Based Medicine, Gastroenterology, Humans, Non-alcoholic Fatty Liver Disease, Predictive Value of Tests, Risk Assessment, Risk Factors, Treatment Outcome, Nonalcoholic Fatty Liver Disease, NAFLD, Nonalcoholic Steatohepatitis, NASH, Clinical Care Pathway, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Find AGA's NASH Clinical Care Pathway App for iOS and Android mobile devices at nash.gastro.org. Scan this QR code to be taken directly to the website.Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common, currently affecting approximately 37% of US adults. NAFLD is most often managed in primary care or endocrine clinics, where clinicians must determine which patients might benefit from secondary care to address hepatic manifestations, comorbid metabolic traits, and cardiovascular risks of the disease. Because NAFLD is largely asymptomatic, and because optimal timing of treatment depends on accurate staging of fibrosis risk, screening at the primary care level is critical, together with consistent, timely, evidence-based, widely accessible, and testable management processes. To achieve these goals, the American Gastroenterological Association assembled a multidisciplinary panel of experts to develop a Clinical Care Pathway providing explicit guidance on the screening, diagnosis, and treatment of NAFLD. This article describes the NAFLD Clinical Care Pathway they developed and provides a rationale supporting proposed steps to assist clinicians in diagnosing and managing NAFLD with clinically significant fibrosis (stage F2-F4) based on the best available evidence. This Pathway is intended to be applicable in any setting where care for patients with NAFLD is provided, including primary care, endocrine, obesity medicine, and gastroenterology practices.

Published
2021

12. Administrative Coding in Electronic Health Care Record‐Based Research of NAFLD: An Expert Panel Consensus Statement

Author

Hagström, Hannes, Adams, Leon A, Allen, Alina M, Byrne, Christopher D, Chang, Yoosoo, Grønbæk, Henning, Ismail, Mona, Jepsen, Peter, Kanwal, Fasiha, Kramer, Jennifer, Lazarus, Jeffrey V, Long, Michelle T, Loomba, Rohit, Newsome, Philip N, Rowe, Ian A, Ryu, Seungho, Schattenberg, Jörn M, Serper, Marina, Sheron, Nick, Simon, Tracey G, Tapper, Elliot B, Wild, Sarah, Wong, Vincent Wai‐Sun, Yilmaz, Yusuf, Zelber‐Sagi, Shira, and Åberg, Fredrik

Subjects
Patient Safety, Clinical Research, Good Health and Well Being, Biomedical Research, Clinical Coding, Consensus, Electronic Health Records, Humans, Non-alcoholic Fatty Liver Disease, Reference Standards, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Background and aimsElectronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues.Approach and resultsResearchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research.ConclusionsThis expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.

Published
2021

14. 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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15. A global research priority agenda to advance public health responses to fatty liver disease

Author

Lazarus, Jeffrey V., Mark, Henry E., Allen, Alina M., Arab, Juan Pablo, Carrieri, Patrizia, Noureddin, Mazen, Alazawi, William, Alkhouri, Naim, Alqahtani, Saleh A., Arrese, Marco, Bataller, Ramon, Berg, Thomas, Brennan, Paul N., Burra, Patrizia, Castro-Narro, Graciela E., Cortez-Pinto, Helena, Cusi, Kenneth, Dedes, Nikos, Duseja, Ajay, Francque, Sven M., Hagström, Hannes, Huang, Terry T-K., Wajcman, Dana Ivancovsky, Kautz, Achim, Kopka, Christopher J., Krag, Aleksander, Miller, Veronica, Newsome, Philip N., Rinella, Mary E., Romero, Diana, Sarin, Shiv Kumar, Silva, Marcelo, Spearman, C. Wendy, Tsochatzis, Emmanuel A., Valenti, Luca, Villota-Rivas, Marcela, Zelber-Sagi, Shira, Schattenberg, Jörn M., Wong, Vincent Wai-Sun, Younossi, Zobair M., Aberg, Fredrik, Adams, Leon, Al-Naamani, Khalid, Albadawy, Reda M., Alexa, Zinaida, Allison, Michael, Alnaser, Faisal A., Alswat, Khalid, Alvares-da-Silva, Mario Reis, Alvaro, Domenico, Alves-Bezerra, Michele, Andrade, Raul J., Anstee, Quentin M., Awuku, Yaw Asante, Baatarkhuu, Oidov, Baffy, Gyorgy, Bakieva, Shokhista, Bansal, Meena B., Barouki, Robert, Batterham, Rachel L., Behling, Cynthia, Belfort-DeAguiar, Renata, Berzigotti, Annalisa, Betel, Michael, Bianco, Cristiana, Bosi, Emanuele, Boursier, Jerome, Brunt, Elizabeth M., Bugianesi, Elisabetta, Byrne, Christopher J., Cabrera Cabrejos, Maria Cecilia, Caldwell, Stephen, Carr, Rotonya, Castellanos Fernández, Marlen Ivón, Castera, Laurent, Castillo-López, Maria Gabriela, Caussy, Cyrielle, Cerda-Reyes, Eira, Ceriello, Antonio, Chan, Wah- Kheong, Chang, Yoosoo, Charatcharoenwitthaya, Phunchai, Chavez-Tapia, Norberto, Chung, Raymond T., Colombo, Massimo, Coppell, Kirsten, Cotrim, Helma P., Craxi, Antonio, Crespo, Javier, Dassanayake, Anuradha, Davidson, Nicholas O., De Knegt, Robert, de Ledinghen, Victor, Demir, Münevver, Desalegn, Hailemichael, Diago, Moises, Dillon, John F., Dimmig, Bruce, Dirac, M. Ashworth, Dirchwolf, Melisa, Dufour, Jean-François, Dvorak, Karel, Ekstedt, Mattias, El-Kassas, Mohamed, Elsanousi, Osama M., Elsharkawy, Ahmed M., Elwakil, Reda, Eskridge, Wayne, Eslam, Mohammed, Esmat, Gamal, Fan, Jian- Gao, Ferraz, Maria Lucia, Flisiak, Robert, Fortin, Davide, Fouad, Yasser, Freidman, Scott L., Fuchs, Michael, Gadano, Adrian, Gastaldelli, Amalia, Geerts, Anja, Geier, Andreas, George, Jacob, Gerber, Lynn H., Ghazinyan, Hasmik, Gheorghe, Liana, Kile, Denise Giangola, Girala, Marcos, Boon Bee, George Goh, Goossens, Nicolas, Graupera, Isabel, Grønbæk, Henning, Hamid, Saeed, Hebditch, Vanessa, Henry, Zachary, Hickman, Ingrid J., Hobbs, L. Ansley, Hocking, Samantha L., Hofmann, Wolf Peter, Idilman, Ramazan, Iruzubieta, Paula, Isaacs, Scott, Isakov, Vasily A., Ismail, Mona H., Jamal, Mohammad H., Jarvis, Helen, Jepsen, Peter, Jornayvaz, François, Sudhamshu, K.C., Kakizaki, Satoru, Karpen, Saul, Kawaguchi, Takumi, Keating, Shelley E., Khader, Yousef, Kim, Seung Up, Kim, Won, Kleiner, David E., Koek, Ger, Joseph Komas, Narcisse Patrice, Kondili, Loreta A., Koot, Bart G., Korenjak, Marko, Kotsiliti, Eleni, Koulla, Yiannoula, Kugelmas, Carina, Kugelmas, Marcelo, Labidi, Asma, Lange, Naomi F., Lavine, Joel E., Lazo, Mariana, Leite, Nathalie, Lin, Han-Chieh, Lkhagvaa, Undram, Long, Michelle T., Lopez-Jaramillo, Patricio, Lozano, Adelina, Macedo, Maria Paula, Malekzadeh, Reza, Marchesini, Giulio, Marciano, Sebastian, Martinez, Kim, Martínez Vázquez, Sophia E., Mateva, Lyudmila, Mato, José M., Nlombi, Charles Mbendi, McCary, Alexis Gorden, McIntyre, Jeff, McKee, Martin, Mendive, Juan M., Mikolasevic, Ivana, Miller, Pamela S., Milovanovic, Tamara, Milton, Terri, Moreno-Alcantar, Rosalba, Morgan, Timothy R., Motala, Ayesha, Muris, Jean, Musso, Carla, Nava-González, Edna J., Negro, Francesco, Nersesov, Alexander V., Neuschwander-Tetri, Brent A., Nikolova, Dafina, Norris, Suzanne, Novak, Katja, Ocama, Ponsiano, Ong, Janus P., Ong-Go, Arlinking, Onyekwere, Charles, Padilla, Martin, Pais, Raluca, Pan, Calvin, Panduro, Arturo, Panigrahi, Manas K., Papatheodoridis, Georgios, Paruk, Imran, Patel, Keyur, Gonçalves, Carlos Penha, Figueroa, Marlene Pérez, Pérez-Escobar, Juanita, Pericàs, Juan M., Perseghin, Gianluca, Pessoa, Mário Guimarães, Petta, Salvatore, Marques Souza de Oliveira, Claudia Pinto, Prabhakaran, Dorairaj, Pyrsopoulous, Nikolaos, Rabiee, Atoosa, Ramji, Alnoor, Ratziu, Vlad, Ravendhran, Natarajan, Ray, Katrina, Roden, Michael, Romeo, Stefano, Romero-Gómez, Manuel, Rotman, Yaron, Rouabhia, Samir, Rowe, Ian A., Sadirova, Shakhlo, Alkhatry, Maryam Salem, Salupere, Riina, Satapathy, Sanjaya K., Schwimmer, Jeffrey B., Sebastiani, Giada, Seim, Lynn, Seki, Yosuke, Serme, Abdel Karim, Shapiro, David, Sharvadze, Lali, Shaw, Jonathan E., Shawa, Isaac Thom, Shenoy, Thrivikrama, Shibolet, Oren, Shimakawa, Yusuke, Shubrook, Jay H., Singh, Shivaram Prasad, Sinkala, Edford, Skladany, Lubomir, Skrypnyk, Igor, Song, Myeong Jun, Sookoian, Silvia, Sridharan, Kannan, Stefan, Norbert, Stine, Jonathan G., Stratakis, Nikolaos, Sheriff, Dhastagir Sultan, Sundaram, Shikha S., Svegliati-Baroni, Gianluca, Swain, Mark G., Tacke, Frank, Taheri, Shahrad, Tan, Soek-Siam, Tapper, Elliot B., Targher, Giovanni, Tcaciuc, Eugen, Thiele, Maja, Tiniakos, Dina, Tolmane, Ieva, Torre, Aldo, Torres, Esther A., Treeprasertsuk, Sombat, Trenell, Michael, Turcan, Svetlana, Turcanu, Adela, Valantinas, Jonas, van Kleef, Laurens A., Velarde Ruiz Velasco, Jose Antonio, Vesterhus, Mette, Vilar-Gomez, Eduardo, Waked, Imam, Wattacheril, Julia, Wedemeyer, Heiner, Wilkins, Fonda, Willemse, José, Wong, Robert J., Yilmaz, Yusuf, Yki-Järvinen, Hannele, Yu, Ming-Lung, Yumuk, Volkan, Zeybel, Müjdat, Zheng, Kenneth I., Zheng, Ming-Hua, and Huang, Terry T.-K.

Published
2023
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16. LBP-014 Enhancing prediction of moderate fibrosis in MASLD patients for Resmetirom treatment via machine learning

Author

Dunn, Winston, primary, Alkhouri, Naim, additional, Yip, Terry Cheuk-Fung, additional, Castera, Laurent, additional, Takawy, Marina, additional, Adams, Leon, additional, Verma, Nipun, additional, Arab, Juan Pablo, additional, Jafri, Syed-Mohammed, additional, Zhong, Bihui, additional, Dubourg, Julie, additional, Chen, Vincent, additional, Singal, Ashwani K., additional, Diaz, Luis Antonio, additional, Dunn, Nicholas, additional, Nadeem, Rida, additional, Wong, Vincent Wai-Sun, additional, Abdelmalek, Manal F., additional, Wang, Zhengyi, additional, Duseja, Ajay Kumar, additional, Almahanna, Yousef, additional, Bajunayd, Amani, additional, Omeish, Haya A., additional, Ye, Junzhao, additional, Harrison, Stephen A., additional, Wong, Grace Lai-Hung, additional, Arrese, Marco, additional, Robert, Sage, additional, and Shao, Congxiang, additional

Published
2024
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17. FRI-263 Severity of hepatic steatosis measured with controlled attenuation parameter as a determinant of carotid atherosclerosis in the Raine Study

Author

Ayonrinde, Oyekoya, primary, Adams, Leon, additional, Zelesco, Marilyn, additional, Welman, Christopher, additional, Mori, Trevor, additional, Melton, Phillip, additional, Mould, Andrea, additional, Beilin, Lawrence, additional, Fiori, James, additional, Dwivedi, Girish, additional, Sanfilippo, Frank, additional, and Olynyk, John, additional

Published
2024
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18. FRI-250 An intergenerational study of the prevalence and cardiometabolic significance of steatotic liver disease in adults in the Raine Study

Author

Ayonrinde, Oyekoya, primary, Adams, Leon, additional, Mori, Trevor, additional, Melton, Phillip, additional, Olynyk, John, additional, Zelesco, Marilyn, additional, Mould, Andrea, additional, Fiori, James, additional, Beilin, Lawrence, additional, Dwivedi, Girish, additional, Sanfilippo, Frank, additional, and Welman, Christopher, additional

Published
2024
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19. WED-267 The FAP Index: A statistical model aiding the detection of advanced liver fibrosis in people with diabetes, obesity or metabolic dysfunction-associated steatosis using a marker of activated stellate cells and myofibroblasts

Author

Wang, Ziqi Vincent, primary, Boumelhem, Badwi, additional, Bachovchin, William, additional, Ooi, Geraldine, additional, George, Jacob, additional, Eslam, Mohammed, additional, Adams, Leon, additional, Zhang, Hui, additional, McCaughan, Geoff, additional, Majumdar, Avik, additional, and Gorrell, Mark, additional

Published
2024
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20. Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

Author

Dave, Shravan, Park, Sooyoung, Murad, M Hassan, Barnard, Abbey, Prokop, Larry, Adams, Leon A, Singh, Siddharth, and Loomba, Rohit

Subjects
Clinical Research, Clinical Trials and Supportive Activities, Rare Diseases, Liver Disease, Cancer, Digestive Diseases, Comparative Effectiveness Research, Liver Cancer, Hepatitis, Good Health and Well Being, Antiviral Agents, Carcinoma, Hepatocellular, Guanine, Hepatitis B, Chronic, Humans, Incidence, Liver Cirrhosis, Liver Neoplasms, Observational Studies as Topic, Randomized Controlled Trials as Topic, Risk, Tenofovir, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Background and aimsChronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta-analysis.Approach and resultsWe searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow-up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person-years) were included for quantitative analysis. On unadjusted meta-analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99-1.66). When using available adjusted data (multivariate or propensity-matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01-1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66-1.23), suggesting no difference between ETV-treated and TDF-treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity).ConclusionsTDF may be associated with lower risk of HCC when compared to ETV.

Published
2021

21. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis

Author

Gaul, Susanne, Leszczynska, Aleksandra, Alegre, Fernando, Kaufmann, Benedikt, Johnson, Casey D, Adams, Leon A, Wree, Alexander, Damm, Georg, Seehofer, Daniel, Calvente, Carolina J, Povero, Davide, Kisseleva, Tatiana, Eguchi, Akiko, McGeough, Matthew D, Hoffman, Hal M, Pelegrin, Pablo, Laufs, Ulrich, and Feldstein, Ariel E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Liver Disease, Chronic Liver Disease and Cirrhosis, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Oral and gastrointestinal, Good Health and Well Being, Animals, Caspase 1, Hepatic Stellate Cells, Hepatocytes, Humans, Inflammasomes, Interleukin-1beta, Liver Cirrhosis, Mice, Mice, Inbred NOD, NLR Family, Pyrin Domain-Containing 3 Protein, Non-alcoholic Fatty Liver Disease, Protein Translocation Systems, Pyroptosis, Reactive Oxygen Species, NLRP3, Inflammasome, Specks, ASC, Fibrosis, NASH, Liver, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background & aimsIncreased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is unknown.MethodsWe used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3KICreA mice, and GsdmdKO mice to investigate pyroptotic cell death in hepatocytes and its impact on liver inflammation and damage. Extracellular NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes were isolated from mutant NLRP3-YFP HEK cells and internalisation was studied in LX2 and primary human hepatic stellate cells. We also examined a cohort of 154 adult patients with biopsy-proven non-alcoholic fatty liver disease (Sir Charles Gairdner Hospital, Nedlands, Western Australia).ResultsWe demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP3 inflammasome proteins that amplify and perpetuate inflammasome-driven fibrogenesis. Pyroptosis was inhibited by blocking caspase-1 and gasdermin D activation. The activated form of caspase-1 was detected in the livers and in serum from patients with non-alcoholic steatohepatitis and correlated with disease severity. Nlrp3KICreA mice showed spontaneous liver fibrosis under normal chow diet, and increased sensitivity to liver damage and inflammation after treatment with low dose lipopolysaccharide. Mechanistically, hepatic stellate cells engulfed extracellular NLRP3 inflammasome particles leading to increased IL-1β secretion and α-smooth muscle actin expression. This effect was abrogated when cells were pre-treated with the endocytosis inhibitor cytochalasin B.ConclusionsThese results identify hepatocyte pyroptosis and release of inflammasome components as a novel mechanism to propagate liver injury and liver fibrosis development.Lay summaryOur findings identify a novel mechanism of inflammation in the liver. Experiments in cell cultures, mice, and human samples show that a specific form of cell death, called pyroptosis, leads to the release of complex inflammatory particles, the NLRP3 inflammasome, from inside hepatocytes into the extracellular space. From there they are taken up by other cells and thereby mediate inflammatory and pro-fibrogenic stress signals. The discovery of this mechanism may lead to novel treatments for chronic liver diseases in the future.

Published
2021

22. Advances in non-invasive assessment of hepatic fibrosis.

Author

Adams, Leon and Loomba, Rohit

Subjects
Nonalcoholic fatty liver disease, chronic liver disease, cirrhosis, elastography, serum biomarkers, Biomarkers, Elasticity Imaging Techniques, Humans, Liver Cirrhosis, Magnetic Resonance Imaging, Risk Assessment
Abstract

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more complex serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.

Published
2020

23. Advances in non-invasive assessment of hepatic fibrosis

Author

Loomba, Rohit and Adams, Leon A

Subjects
Obesity, Chronic Liver Disease and Cirrhosis, Liver Disease, Digestive Diseases, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Oral and gastrointestinal, Good Health and Well Being, Biomarkers, Elasticity Imaging Techniques, Humans, Liver Cirrhosis, Magnetic Resonance Imaging, Risk Assessment, chronic liver disease, elastography, serum biomarkers, cirrhosis, Nonalcoholic fatty liver disease, Clinical Sciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more 'complex' serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.

Published
2020

27. The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement

Author

Hagström, Hannes, primary, Adams, Leon A., additional, Allen, Alina M., additional, Byrne, Christopher D., additional, Chang, Yoosoo, additional, Duseja, Ajay, additional, Grønbæk, Henning, additional, Ismail, Mona H., additional, Jepsen, Peter, additional, Kanwal, Fasiha, additional, Kramer, Jennifer, additional, Loomba, Rohit, additional, Mark, Henry E., additional, Newsome, Philip N., additional, Rinella, Mary E., additional, Rowe, Ian A., additional, Ryu, Seungho, additional, Sanyal, Arun, additional, Schattenberg, Jörn M., additional, Serper, Marina, additional, Sheron, Nick, additional, Simon, Tracey G., additional, Spearman, C. Wendy, additional, Tapper, Elliot B., additional, Villota-Rivas, Marcela, additional, Wild, Sarah H., additional, Wong, Vincent Wai-Sun, additional, Yilmaz, Yusuf, additional, Zelber-Sagi, Shira, additional, Åberg, Fredrik, additional, and Lazarus, Jeffrey V., additional

Published
2024
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28. Author Correction: Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author

Valenti, Luca, primary, Corradini, Elena, additional, Adams, Leon A., additional, Aigner, Elmar, additional, Alqahtani, Saleh, additional, Arrese, Marco, additional, Bardou-Jacquet, Edouard, additional, Bugianesi, Elisabetta, additional, Fernandez-Real, Jose-Manuel, additional, Girelli, Domenico, additional, Hagström, Hannes, additional, Henninger, Benjamin, additional, Kowdley, Kris, additional, Ligabue, Guido, additional, McClain, Donald, additional, Lainé, Fabrice, additional, Miyanishi, Koji, additional, Muckenthaler, Martina U., additional, Pagani, Alessia, additional, Pedrotti, Patrizia, additional, Pietrangelo, Antonello, additional, Prati, Daniele, additional, Ryan, John D., additional, Silvestri, Laura, additional, Spearman, C. Wendy, additional, Stål, Per, additional, Tsochatzis, Emmanuel A., additional, Vinchi, Francesca, additional, Zheng, Ming-Hua, additional, and Zoller, Heinz, additional

Published
2023
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32. The Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand

Author

Howell, Jess, Majumdar, Avik, Fink, Michael, Byrne, Mandy, McCaughan, Geoff, Strasser, Simone I., Crawford, Michael, Hodgkinson, Peter, Stuart, Katherine A., Tallis, Caroline, Chen, John, Wigg, Alan, Jones, Robert, Jaques, Bryon, Jeffrey, Gary, Adams, Leon, Wallace, Michael C., Gane, Ed, Thompson, Alex, and Gow, Paul

Published
2022
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34. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease

Author

Eslam, Mohammed, Sarin, Shiv K., Wong, Vincent Wai-Sun, Fan, Jian-Gao, Kawaguchi, Takumi, Ahn, Sang Hoon, Zheng, Ming-Hua, Shiha, Gamal, Yilmaz, Yusuf, Gani, Rino, Alam, Shahinul, Dan, Yock Young, Kao, Jia-Horng, Hamid, Saeed, Cua, Ian Homer, Chan, Wah-Kheong, Payawal, Diana, Tan, Soek-Siam, Tanwandee, Tawesak, Adams, Leon A., Kumar, Manoj, Omata, Masao, and George, Jacob

Published
2020
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35. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement

Author

Eslam, Mohammed, Newsome, Philip N., Sarin, Shiv K., Anstee, Quentin M., Targher, Giovanni, Romero-Gomez, Manuel, Zelber-Sagi, Shira, Wai-Sun Wong, Vincent, Dufour, Jean-François, Schattenberg, Jörn M., Kawaguchi, Takumi, Arrese, Marco, Valenti, Luca, Shiha, Gamal, Tiribelli, Claudio, Yki-Järvinen, Hannele, Fan, Jian-Gao, Grønbæk, Henning, Yilmaz, Yusuf, Cortez-Pinto, Helena, Oliveira, Claudia P., Bedossa, Pierre, Adams, Leon A., Zheng, Ming-Hua, Fouad, Yasser, Chan, Wah-Kheong, Mendez-Sanchez, Nahum, Ahn, Sang Hoon, Castera, Laurent, Bugianesi, Elisabetta, Ratziu, Vlad, and George, Jacob

Published
2020
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36. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials

Author

Gadano, Adrian, Martins, Marcelo, Angus, Peter, Bate, John, Danta, Mark, George, Jacob, Hodge, Alexander, Kontorinis, Nickolas, Roberts, Stuart, Sanagapalli, Santosh, Skoien, Richard, Thompson, Alexander, Zekry, Amany, Stauber, Rudolf, Trauner, Michael, Moreno, Christophe, Reynaert, Hendrik, Verbeke, Len, Silva, Mario Reis Alvares da, Parise, Edison, Oliveira, Claudia Pinto Marques Souza de, Araujo, Roberta Chaves, Martinelli, Ana de Lourdes Candolo, Borman, Meredith, Chandok, Natasha, Elkhashab, Magdy, Fraser, Hughie, Kaita, Kelly, Ma, Mang, Marotta, Paul, Ramji, Alnoor, Tam, Edward, Yoshida, Eric, Swain, Mark, Sebastiani, Giada, Petrunia, Denis, Abergel, Armando, Anty, Rodolphe, Bourlière, Marc, Boursier, Jérôme, Bureau, Christophe, Castera, Laurent, Habersetzer, François, Hézode, Christophe, Ledinghen, Victor De, Leroy, Vincent, Loustaud-Ratti, Véronique, Mathurin, Philippe, Pol, Stanislas, Zoulim, Fabien, Hinrichsen, Holger, Ingiliz, Patrick, Lammert, Frank, Manns, Michael, Schattenberg, Jörn, Schiefke, Ingolf, Trautwein, Christian, Zeuzem, Stefan, Hui, Aric, Li, King-Kong, Wong, Vincent, Acharya, Subrat, Chowdhury, Abhijit, Duseja, Ajay, Kapoor, Dharmesh, Mukewar, Shrikant, Sarin, Shiv, Shah, Samir, Shalimar, Sood, Ajit, Tantry, BV, Ben-Ari, Ziv, Katchman, Helena, Safadi, Rifaat, Veitsman, Ella, Zuckerman, Eli, Brunetto, Maurizia, Lampertico, Pietro, Mangia, Alessandra, Akahane, Takemi, Akuta, Norio, Eguchi, Yuichiro, Fujiyama, Shigetoshi, Genda, Takuya, Hiasa, Yoichi, Ido, Akio, Ikeda, Fusao, Ikegami, Tadashi, Imajo, Kento, Itoh, Yoshito, Iwasa, Motoh, Karino, Yoshiyasu, Kato, Naoya, Kawaguchi, Takumi, Kawanaka, Miwa, Kido, Masahiro, Kobayashi, Tomoo, Kurosaki, Masayuki, Matsuzaki, Yasushi, Mita, Eiji, Mizukoshi, Eishiro, Nakahara, Takashi, Nomura, Hideyuki, Notsumata, Kazuo, Okanoue, Takeshi, Saito, Satoshi, Sakugawa, Hiroshi, Suzuki, Yoshiyuki, Takaguchi, Koichi, Takaki, Akinobu, Takashima, Tomoyuki, Tanaka, Saiyu, Tsuji, Keiji, Ueno, Yoshiyuki, Umemura, Takeji, Uto, Hirofumi, Yamashita, Nobuyuki, Yanase, Mikio, Yatsuhashi, Hiroshi, Yoneda, Masashi, Chan, Wah Kheong, Tan, Soek Siam, Garza, Laura Cisneros, Ladron De Guevara Cetina, Alma, Angeles, Rocio Guadalupe Vargas, Silva, Francisca Martinez, Van Erpecum, Karel, Orr, David, Jabłkowski, Maciej, Jaroszewicz, Jerzy, Ramos, Jose, Ahmed, Taufique, Ang, Tiing, Dan, Yock young, Goh, Boon Bee, Kaliyaperumal, Kalaiyarasi, Yip, Cherng Hann, Baik, Soon Koo, Jang, Byoung Kuk, Jun, Dae Won, Kim, Won, Kim, Hyung Joon, Kim, Ji Hoon, Lee, Kwan Sik, Lee, Chun Kyon, Lim, Young-Suk, Park, Jun Yong, Tak, Won Young, Augustin, Salvador, Perez, Salvador Benlloch, Caballeria, Juan, Luis, Jose, Panero, Calleja, Rodríguez, Jose Carrión, Garcia, Javier Crespo, Samaniego, Javier Garcia, Gibert, Pere Ginès, Prieto, Martin, Gomez, Manuel Romero, Turnes, Juan, Dufour, Jean-Francois, Moriggia, Alberto, Sheen, I-Shyan, Kao, Jia-Horng, Cheng, Pin-Nan, Huang, Jee-Fu, Yang, Sheng-Shun, Su, Wei-Wen, Chen, Chi-Yi, Chien, Rong-Nan, Lo, Gin-Ho, Chu, Chi-Jen, Wang, Horng-Yuan, Hu, Jui-Ting, Huang, Yi Wen, Agarwal, Kosh, Allison, Michael, Anstee, Quentin, Austin, Andrew, Fowell, Andrew, Ch'ng, Chin Lye, Manousou, Pinelopi, Newsome, Philip, Ryder, Stephen, Shankar, Arun, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Alam, Imtiaz, Alba, Laura, Alkhouri, Naim, Allen, Alina, Aqel, Bashar, Balart, Luis, Barritt, A. Sidney, IV, Behari, Jaideep, Bennett, Michael, Bernstein, David, Bhandari, Bal Raj, Bonacini, Maurizio, Borg, Brian, Brown, Kimberly, Bzowej, Natalie, Caldwell, Stephen, Chami, Tawfik, Coates, Allan, Cueli, Adolfo, Davis, Mitchell, deLemos, Andrew, Desai, Archita, Dunn, Winston, Ferreira, Nelson, Fine, Michael, Firpi-Morell, Roberto, Freedland, Curtis, Freilich, Bradley, Fuchs, Michael, Galambos, Michael, Gallegos-Orozco, Juan, Galler, Greg, Ghali, Maged, Ghalib, Reem, Gill, Satinder, Gillis, Marcum, Gilroy, Richard, Gordon, Stuart, Gunn, Nadege, Halegoua-DeMarzio, Dina, Hassan, Mohamed, Hassanein, Tarek, Herring, Robert, Jr., Hong, John, Huang, Jonathan, Kabler, Heidi, Kayali, Zeid, Knapple, Whitfield, Kolli, Geetha, Kowdley, Kris, Krause, Richard, Lawitz, Eric, Lidofsky, Steven, Lim, Joseph, Lipkis, Donald, Loomba, Rohit, Mahgoub, Amar, Malespin, Miguel, Manch, Richard, Mannis, Steven, Manos, Paul, McDonald, Thomas, McKenzie, Mark, Mena, Edward, Merriman, Raphael, Moehlen, Martin William, Montgomery, Richard, Murphy, Robert, Natarajan, Yamini, Neff, Guy, Noureddin, Mazen, Ortiz-Lasanta, Grisell, Pagadala, Mangesh, Patel, Keyur, Patton, Heather, Peyton, Adam, Pimstone, Neville, Poulos, John, Pound, David, Pyrsopoulos, Nikolaos, Rafiq, Nila, Ravendhran, Natarajan, Ravinuthala, Ravi, Reddy, K. Rajendar, Reindollar, Robert, Reynolds, Justin, Rinella, Mary, Rizvi, Syed, Rockey, Don, Rodriguez-Perez, Federico, Ruane, Peter, Rubin, Raymond, Ryan, Michael, Saeian, Kia, Sanyal, Arun, Sarkar, Souvik, Scanga, Andrew, Schiff, Eugene, Schmidt, Warren, Schneider, Jeffrey, Sepe, Thomas, Shah, Dhiren, Shaikh, Obaid, Shankar, Uday, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shiffman, Mitchell, Siddique, Asma, Smith, Matthew, Suarez, Rosa, Talal, Andrew, Te, Helen, Tekola, Bezawit, Tetri, Brent, Thuluvath, Paul, Toro, Doris, Torres, Dawn, Trinh, Huy, Trotter, James, Vento, Angel, Vierling, John, Vuppalanchi, Raj, Waters, Michael, Weisberg, Ilan, Wieland, Amanda, Williams, Alonzo, Younes, Ziad, Adams, Leon, Harding, Damian, Hodge, Alex, Kontorinis, Nick, Strasser, Simone, Thompson, Alex, Horsmans, Yves, Steenkiste, Christophe Van, Bailey, Robert, Giard, Jeanne-Marie, Montano-Loza, Aldo, Puglia, Marco, Tsoi, Keith, Larrey, Dominique, Nguyen-Khac, Eric, Ratziu, Vlad, Spengler, Ulrich, Wiegand, Johannes, Hui, Aric Josun, Acharya, Subrat Kumar, Sarin, Shiv Kumar, Tantry, Vishwanath, Braun, Marius, Hazzan, Rawi, Lurie, Yoav, Colombo, Massimo, Fujii, Hideki, Hashimoto, Etsuko, Kato, Masaki, Ogawa, Koji, Takehara, Tetsuo, Tokushige, Katsutoshi, Garza, Laura Esthela Cisneros, Ladrón De Guevara, Alma Laura, Schultz, Michael, Janczewska, Ewa, Toro, Doris H., Jeong, Sook-Hyang, Kim, Yoon Jun, Lee, Jin-Woo, Ang, Tiing Leong, Bee, George Goh Boon, Benlloch, Salvador, Caballería, Juan, Calleja, José Luis, Rodríguez, Jose A. Carrión, Crespo, Javier, Diago, Moises, Fernandez-Rodriguez, Conrado, García-Samaniego, Javier, Ginès, Pere, Romero, Manuel, Dufour, Jean-François, Alazawi, William, Ch'ng, Chin-Lye, Forton, Daniel, Priest, Matthew, Sheridan, David, Ankoma-Sey, Victor, Balakrishnan, Maya, Bambha, Kiran, Barritt, A. Sidney, Bhandari, Bal, Brandman, Danielle, Chang, Charissa, Corey, Kathleen, Feldman, Michael, Gholam, Pierre, Goff, John, Marzio, Dina Halegoua-De, Harrison, Stephen, Hellstern, Paul, Jr., Herring, Robert, Iyer, Rajalakshmi, Jakiche, Antoine, Kohli, Anita, Krok, Karen, Kugelmas, Marcelo, Kumar, Sonal, Lai, Michelle, Mahmoud, Mitchell, Mantry, Parvez, Marsano, Luis, Nguyen, Tuan, Park, James, Patton, Heather M., Pockros, Paul, Reddy, Rajender, Rodriguez, Miguel, Sarles, Harry, Satapathy, Sanjaya, Sedghi, Shahriar, Shah, Nikunj, Sheikh, Muhammad Yasin, Sigal, Samuel, Stanca, Carmen, Steinbook, Michael, Szabo, Gyongyi, Terrault, Norah, Tong, Myron, Victor, David, Zervos, Xaralambos, Harrison, Stephen A., Wong, Vincent Wai-Sun, Caldwell, Stephen H., Shiffman, Mitchell L., Camargo, Marianne, Li, Georgia, Kersey, Kathryn, Jia, Catherine, Zhu, Yanni, Djedjos, C. Stephen, Subramanian, G. Mani, Myers, Robert P., Anstee, Quentin M., Romero-Gomez, Manuel, Goodman, Zachary, Lawitz, Eric J., and Younossi, Zobair

Published
2020
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42. A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR

Author

Metwally, Mayada, Bayoumi, Ali, Romero-Gomez, Manuel, Thabet, Khaled, John, Miya, Adams, Leon A., Huo, Xiaoqi, Aller, Rocio, García-Monzón, Carmelo, Teresa Arias-Loste, María, Bugianesi, Elisabetta, Miele, Luca, Gallego-Durán, Rocio, Fischer, Janett, Berg, Thomas, Liddle, Christopher, Qiao, Liang, George, Jacob, and Eslam, Mohammed

Published
2019
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45. Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study

Author

Vilar-Gomez, Eduardo, Calzadilla-Bertot, Luis, Wai-Sun Wong, Vincent, Castellanos, Marlen, Aller-de la Fuente, Rocio, Metwally, Mayada, Eslam, Mohammed, Gonzalez-Fabian, Licet, Alvarez-Quiñones Sanz, María, Conde-Martin, Antonio Felix, De Boer, Bastiaan, McLeod, Duncan, Hung Chan, Anthony Wing, Chalasani, Naga, George, Jacob, Adams, Leon A., and Romero-Gomez, Manuel

Published
2018
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46. Altered expression of ion channels in hyperinsulinism

Author

Adams, Leon and Dunne, Mark

Subjects
616.4
Abstract

The ability of the pancreatic β-cell to secrete insulin in response to changes in glucose concentration is the cornerstone of glucose homeostasis. The β-cell couples glucose metabolism to electrical activity via the modulation of ion channel activity. Defects in β-cell ion channels can result in the dysregulation of insulin secretion and, consequently, in glucose homeostasis. Congenital hyperinsulinism of infancy (CHI) is an inherited disorder of inappropriate insulin secretion often caused by gene defects in the subunits of KATP channels (ABCC8, KCNJ11). In 50% of CHI patients, no genetic basis has yet been discovered. I aimed to characterise the expression, and function, of two novel ion channel families in the healthy human pancreas and the hyperinsulinaemic pancreas.Hyperpolarisation-activated cyclic nucleotide-gated channels (HCN channels) are selective for K+ /Na+ under physiological conditions and are responsible for the rhythmic electrical behaviour (pacemaker behaviour) in the heart and brain. Two-pore potassium channels (K2P channels) are potassium-selective channels whose activity contributes to, and maintains, the resting membrane potential of living cells. HCN and K2P gene and protein expression was investigated by RT-PCR and immunofluorescence. HCN1, 2, 3, and 4 mRNA and mRNA from six K2P channels was detected in isolated mouse islets. Immunofluorescence revealed the presence of HCN1, HCN2 and HCN4 in mouse β-cells. The role of HCN channels in glucose-stimulated insulin secretion (GSIS) was assessed in isolated mouse islets. The HCN channel agonist lamotrigine had no effect on GSIS (n=3), but GSIS was significantly inhibited by the HCN channel blocker zatebradine (n=3) thereby confirming that HCN channels may play a role in glucose homeostasis. Tissue was isolated from adult control human pancreas and from six patients following pancreatectomy for CHI. HCN and K2P channel expression was also assessed in pancreatic tissue from ABCC8-knockout mice. HCN1-4 mRNA and the mRNA of four K2P channels were detected in islets isolated from adult control and CHI patient pancreatic tissue. Co-expression of HCN channel isoforms with insulin confirmed that HCN1, -2 and -4 were β-cell-specific in control human islets. By contrast, in all patient tissues expression of HCN channels was altered, and in 5 out of 6 cases, HCN channels were not expressed in β-cells. The K2P channel TWIK-1 was found to be expressed predominantly in the healthy human exocrine pancreas. In contrast, its expression was consistently detected in the β-cells of CHI patients. We found similar data for both HCN channels and TWIK-1 in islets of ABCC8-knockout mice, but not their litter-mate controls (n=3).These studies provide the first data on the expression of HCN and K2P channels in the human pancreas and reveal that CHI is associated with an altered expression profile of both ion channel families. Significantly, we found that HCN and K2P expression in β-cells is altered in CHI patients and we speculate that this is as a consequence of physiological remodelling.

Published
2011

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