13 results on '"Wonders, Kristy"'
Search Results
2. 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
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Pavlides, Michael, Mózes, 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, González, Rebeca Sigüenza, Agustin, Salvador, Pericàs, Juan M., Boursier, Jerome, Aube, Christophe, Ratziu, Vlad, Wagner, Mathilde, Petta, Salvatore, Antonucci, Michela, Bugianesi, Elisabetta, Faletti, Riccardo, Miele, Luca, Geier, Andreas, Schattenberg, Jörn M., Tilman, Emrich, Ekstedt, Mattias, Lundberg, Peter, Berzigotti, Annalisa, Huber, Adrian T., Papatheodoridis, George, Yki-Järvinen, Hannele, Porthan, Kimmo, Schneider, Moritz Jörg, Hockings, Paul, Shumbayawonda, Elizabeth, Banerjee, Rajarshi, Pepin, Kay, Kalutkiewicz, Mike, Ehman, Richard L., Trylesinksi, Aldo, Coxson, Harvey O., Martic, Miljen, Yunis, Carla, Tuthill, Theresa, Bossuyt, Patrick M., Anstee, Quentin M., Neubauer, Stefan, and Harrison, Stephen
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- 2023
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3. 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
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Anstee, Quentin M, Daly, Ann K, Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J, Day, Christopher P, Wonders, Kristy, Missier, Paolo, McTeer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M, Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G, Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M, Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K, Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioannis, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J, Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, McGlinchey, Aiden, Mato, Jose M, Millet, Óscar, Dufour, Jean-François, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Rasmussen, Daniel Guldager Kring, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattias, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M P, Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andreas, Trautwein, Christian, Reißing, Johanna, Aithal, Guruprasad P, Francis, Susan, Palaniyappan, Naaventhan, Bradley, Christopher, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W, Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, McLeod, Euan James, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Coxson, Harvey, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Kjær, Mette Skalshøi, Harder, Lea Mørch, Davidsen, Peter, Ellegaard, Jens, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Douglas, Shankar, Sudha, Torstenson, Richard, Lindén, Daniel, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D, Billin, Andrew, Doward, Lynda, Twiss, James, Thakker, Paresh, Derdak, Zoltan, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, Mózes, Ferenc E, Lee, Jenny A, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, van Dijk, Anne-Marieke, Mak, Anne Linde, de Saint Loup, Marc, Shima, Toshihide, Gaia, Silvia, Shalimar, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Lee, Dae Ho, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, and Harrison, Stephen A
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- 2023
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4. Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study
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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
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- 2023
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5. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
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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.
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- 2022
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6. Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study.
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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, and Leeming, Diana Julie
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- 2023
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7. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
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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., Boursier, Jerome, Ratziu, Vlad, Bugianesi, Elisabetta, Anstee, Quentin M., Daly, Ann K., Clark, James, Cockell, Simon, 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, McGlinchey, Aidan, Sen, Partho, Mato, Jose, 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, 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, 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, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, Yunis, Carla, Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, and Twiss, James
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Hepatology ,Gastroenterology ,Internal Medicine ,Immunology and Allergy ,digestive system diseases - 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. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
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- 2022
8. The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease
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Hardy, Timothy, Wonders, Kristy, Younes, Ramy, Aithal, Guruprasad P, Aller, Rocio, Allison, Michael, Bedossa, Pierre, Betsou, Fay, Boursier, Jerome, Brosnan, M Julia, Burt, Alastair, Cobbold, Jeremy, Cortez-Pinto, Helena, Day, Chris P, Dufour, Jean-Francois, Ekstedt, Mattias, Francque, Sven, Harrison, Stephen, Miele, Luca, Nasr, Patrik, Papatheodoridis, George, Petta, Salvatore, Tiniakos, Dina, Torstenson, Richard, Valenti, Luca, Holleboom, Adriaan G, Yki-Jarvinen, Hannele, Geier, Andreas, Romero-Gomez, Manuel, Ratziu, Vlad, Bugianesi, Elisabetta, Schattenberg, Jörn M, Anstee, Quentin M, LITMUS Consortium, Newcastle University [Newcastle], Università degli studi di Torino (UNITO), University of Nottingham, UK (UON), Universidad de Valladolid [Valladolid] (UVa), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Integrated BioBank of Luxembourg (IBBL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Pfizer, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], Universidade de Lisboa (ULISBOA), University of Bern, Linköping University (LIU), University of Antwerp (UA), Università cattolica del Sacro Cuore [Roma] (Unicatt), National and Kapodistrian University of Athens (NKUA), Università degli studi di Palermo - University of Palermo, University of Milan, University of Helsinki, University of Würzburg, Hospital Universitario Virgen del Rocío [Sevilla], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University Medical Center [Mainz], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Vascular Medicine, ACS - Diabetes & metabolism, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, LITMUS Consortium, Innovative Medicines Initiative, European Commission, Department of Medicine, HUS Internal Medicine and Rehabilitation, Helsinki University Hospital Area, Hardy T., Wonders K., Younes R., Aithal G.P., Aller R., Allison M., Bedossa P., Betsou F., Boursier J., Brosnan M.J., Burt A., Cobbold J., Cortez-Pinto H., Day C.P., Dufour J.-F., Ekstedt M., Francque S., Harrison S., Miele L., Nasr P., Papatheodoridis G., Petta S., Tiniakos D., Torstenson R., Valenti L., Holleboom A.G., Yki-Jarvinen H., Geier A., Romero-Gomez M., Ratziu V., Bugianesi E., Schattenberg J.M., Anstee Q.M., Harrison, Seamus Conor [0000-0003-1480-1143], and Apollo - University of Cambridge Repository
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Liver Cirrhosis ,PROGNOSIS ,Cirrhosis ,SCORING SYSTEM ,[SDV]Life Sciences [q-bio] ,PROGRESSION ,Disease ,Biomarker, Cirrhosis, NAFLD, NASH ,STEATOHEPATITIS ,DEFINITIONS ,Cohort Studies ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Nonalcoholic fatty liver disease ,Pharmacology (medical) ,030212 general & internal medicine ,Longitudinal Studies ,Registries ,ComputingMilieux_MISCELLANEOUS ,media_common ,Pharmacology. Therapy ,Fatty liver ,Liver Neoplasms ,NASH ,General Medicine ,3. Good health ,Liver ,317 Pharmacy ,Cohort ,0305 other medical science ,Cohort study ,medicine.medical_specialty ,Settore MED/12 - GASTROENTEROLOGIA ,Geriatrik ,QUESTIONNAIRE ,NAFLD ,Biomarker ,610 Medicine & health ,03 medical and health sciences ,medicine ,STEATOSIS ,media_common.cataloged_instance ,Humans ,ALGORITHM ,European union ,Intensive care medicine ,030505 public health ,business.industry ,CONSUMPTION ,STAGING SYSTEM ,medicine.disease ,Diabetes Mellitus, Type 2 ,Geriatrics ,3121 General medicine, internal medicine and other clinical medicine ,3111 Biomedicine ,Human medicine ,Steatohepatitis ,business - Abstract
© 2020 The Author(s)., Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS ‘Liver Investigation: Testing Marker Utility in Steatohepatitis’ consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace., The European NAFLD Registry is supported by the LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377, which receives support from the Horizon 2020 Framework Program of European Union and EFPIA. It has also received support from the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413, the FLIP consortium funded by the Framework Program 7 of the European Union under grant agreement 241762, and an EASL Registry Grant from the European Association for the Study of the Liver.
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- 2020
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9. Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis.
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Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Queen, Rachel, Younes, Ramy, Vacca, Michele, Alexander, Leigh, Ravaioli, Federico, Palmer, Jeremy, Petta, Salvatore, Boursier, Jerome, Rosso, Chiara, Johnson, Katherine, Wonders, Kristy, Day, Christopher P., Ekstedt, Mattias, Orešič, Matej, Darlay, Rebecca, Cordell, Heather J., and Marra, Fabio
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NON-alcoholic fatty liver disease ,INFLAMMATION ,HEPATITIS ,TYPE 2 diabetes ,ASPARTATE aminotransferase ,ENDOPLASMIC reticulum ,GLUCOSE-regulated proteins ,DISEASE progression - Abstract
Gene expression during disease progression: Nonalcoholic fatty liver disease (NAFLD) manifests as an array of conditions ranging from hepatic fat buildup to liver inflammation and scarring. Govaere et al. detected a signature of 25 genes whose expression in diseased tissue associated with worsening of histologically defined NAFLD severity in two independent cohorts of patients. Protein expression of GDF15, a member of the transforming growth factor–β superfamily, also associated with ballooning, inflammation, and fibrosis in NAFLD serum samples. Together, these studies provide a comprehensive analysis of gene expression during human NAFLD progression. The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs738409, a genetic variant associated with NAFLD. Relative to early disease, we consistently identified 25 differentially expressed genes as fibrosing steatohepatitis progressed through stages F2 to F4. This 25-gene signature was independently validated by logistic modeling in a separate replication cohort (n = 175), and an integrative analysis with publicly available single-cell RNA sequencing data elucidated the likely relative contribution of specific intrahepatic cell populations. Translating these findings to the protein level, SomaScan analysis in more than 300 NAFLD serum samples confirmed that circulating concentrations of proteins AKR1B10 and GDF15 were strongly associated with disease activity and fibrosis stage. Supporting the biological plausibility of these data, in vitro functional studies determined that endoplasmic reticulum stress up-regulated expression of AKR1B10, GDF15, and PDGFA, whereas GDF15 supplementation tempered the inflammatory response in macrophages upon lipid loading and lipopolysaccharide stimulation. This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression. [ABSTRACT FROM AUTHOR]
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- 2020
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10. The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease
- Author
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Hardy, Timothy, Wonders, Kristy, Younes, Ramy, Aithal, Guruprasad P, Aller, Rocio, Allison, Michael, Bedossa, Pierre, Betsou, Fay, Boursier, Jerome, Brosnan, M Julia, Burt, Alastair, Cobbold, Jeremy, Cortez-Pinto, Helena, Day, Chris P, Dufour, Jean-François, Ekstedt, Mattias, Francque, Sven, Harrison, Stephen, Miele, Luca, Nasr, Patrik, Papatheodoridis, George, Petta, Salvatore, Tiniakos, Dina, Torstenson, Richard, Valenti, Luca, Holleboom, Adriaan G, Yki-Jarvinen, Hannele, Geier, Andreas, Romero-Gomez, Manuel, Ratziu, Vlad, Bugianesi, Elisabetta, Schattenberg, Jörn M, and Anstee, Quentin M
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610 Medicine & health ,3. Good health - Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS 'Liver Investigation: Testing Marker Utility in Steatohepatitis' consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
11. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
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Raluca Pais, Rachel Ostroff, Stephen Harrison, Lars Friis Mikkelsen, Elisabeth Erhardtsen, Sudha Shankar, Kimmo Porthan, Jérôme Boursier, Antonia Sinisi, Michael Kalutkiewicz, Sven Francque, Miljen Martic, Vanessa Pellegrinelli, Phil N. Newsome, Guido Hanauer, Hannele Yki-Järvinen, Rebecca Darlay, Joel Myers, Carla Yunis, Salvatore Petta, Mette Skalshøi Kjær, Pablo Ortiz, Ann K. Daly, James H. Clark, Dina Tiniakos, Yasaman Vali, Hadi Zafarmand, Matej Orešič, Maurizio Parola, Estelle Sandt, Lori L. Jennings, Matt Kelly, Tuulia Hyötyläinen, Detlef Schuppan, Céline Fournier, Chiara Rosso, Diane E. Shevell, Maria Manuela Tonini, Paul Hockings, Aidan McGlinchey, Salma Akhtar, Mette Juul Fisker, Morten A. Karsdal, Diane Whalley, Melissa R. Miller, Aldo Trylesinski, Mattias Ekstedt, Stefan Neubauer, Jeremy M. Palmer, Partho Sen, Michael Pavlides, Per Qvist, Isabel Fernández, Luca Miele, Fabio Marra, Stergios Kechagias, Richard Torstenson, Katherine Johnson, Jean-François Dufour, Elisabetta Bugianesi, M. Julia Brosnan, George V. Papatheodoridis, Kay M. Pepin, Daniel Guldager Kring Rasmussen, Henrik Landgren, Rachel Queen, Simon Cockell, Michael Allison, Patrick M.M. Bossuyt, Rocío Gallego-Durán, Christian Rosenquist, Leigh Alexander, Elizabeth Shumbayawonda, Michele Vacca, Antonio Vidal-Puig, David Wenn, Rémy Hanf, Oscar Millet, Michalina Zatorska, R. Myers, José M. Mato, Jenny Lee, Theresa Tuthill, James Twiss, Ramy Younes, Peter Leary, Lynda Doward, Kristy Wonders, Guruprasad P. Aithal, Sarah Charlton, Vlad Ratziu, Cecília M. P. Rodrigues, Christian Trautwein, Helena Cortez-Pinto, Gideon Ho, Matt J. Barter, Judith Ertle, Jörn M. Schattenberg, Maria-Magdalena Balp, Yang-Lin Liu, Clifford A. Brass, Olivier Govaere, Amalia Gastaldelli, Sergio Rodriguez Cuenca, Pierre Chaumat, Fiona Oakley, Luca Valenti, Simon J. Cockell, Saskia W.C. van Mil, Ferenc E. Mózes, Andreas Geier, Timothy Hardy, Pierre Bedossa, Andrea Dennis, Richard L. Ehman, Charlotte Erpicum, Karine Clément, Jeremy F. L. Cobbold, Christopher P. Day, Rajarshi Banerjee, Manuel Romero-Gómez, Quentin M. Anstee, Adriaan G. Holleboom, Heather J. Cordell, Kevin L. Duffin, Diana Julie Leeming, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Graduate School, Investigators, LITMUS Consortium, Johnson K., Leary P.J., Govaere O., Barter M.J., Charlton S.H., Cockell S.J., Tiniakos D., Zatorska M., Bedossa P., Brosnan M.J., Cobbold J.F., Ekstedt M., Aithal G.P., Clement K., Schattenberg J.M., Boursier J., Ratziu V., Bugianesi E., Anstee Q.M., Daly A.K., Clark J., Cordell H.J., Darlay R., Day C.P., Hardy T., Liu Y.-L., Oakley F., Palmer J., Queen R., Wonders K., Bossuyt P.M., Holleboom A.G., Zafarmand H., Vali Y., Lee J., Pais R., Schuppan D., Allison M., Cuenca S.R., Pellegrinelli V., Vacca M., Vidal-Puig A., Hyotylainen T., McGlinchey A., Oresic M., Sen P., Mato J., Millet O., Dufour J.-F., Harrison S., Neubauer S., Pavlides M., Mozes F., Akhtar S., Banerjee R., Kelly M., Shumbayawonda E., Dennis A., Erpicum C., Romero-Gomez M., Gallego-Duran R., Fernandez I., Karsdal M., Leeming D., Fisker M.J., Erhardtsen E., Rasmussen D., Qvist P., Sinisi A., Sandt E., Tonini M.M., Parola M., Rosso C., Marra F., Gastaldelli A., Francque S., Kechagias S., Yki-Jarvinen H., Porthan K., van Mil S., Papatheodoridis G., Cortez-Pinto H., Valenti L., Petta S., Miele L., Geier A., Trautwein C., Hockings P., Newsome P., Wenn D., Pereira Rodrigues C.M., Hanf R., Chaumat P., Rosenquist C., Trylesinski A., Ortiz P., Duffin K., Yunis C., Miller M., Tuthill T., Ertle J., Younes R., Alexander L., Ostroff R., Kjaer M.S., Mikkelsen L.F., Brass C., Jennings L., Balp M.-M., Martic M., Hanauer G., Shankar S., Torstenson R., Fournier C., Ehman R., Kalutkiewicz M., Pepin K., Myers J., Shevell D., Ho G., Landgren H., Myers R., Doward L., Whalley D., Twiss J., 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, 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, and Yunis, Carla
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SCORING SYSTEM ,CPM, counts per million ,AUROC, area under the receiver operating characteristic ,RC799-869 ,AST, aspartate aminotransferase ,MicroRNA ,Non-alcoholic fatty liver disease ,Biomarker ,Sequencing ,TGF-β, transforming growth factor-beta ,Gastroenterology ,STEATOHEPATITIS ,Liver disease ,0302 clinical medicine ,Fibrosis ,miRNA, microRNA ,logFC, log2 fold change ,FIBROSIS ,Immunology and Allergy ,0303 health sciences ,education.field_of_study ,NAS, NAFLD activity score ,medicine.diagnostic_test ,Fatty liver ,GTEx, Genotype-Tissue Expression ,Diseases of the digestive system. Gastroenterology ,3. Good health ,Real-time polymerase chain reaction ,Biomarker, MicroRNA, Non-alcoholic fatty liver disease, Sequencing ,Liver biopsy ,ACID ,Biomarker (medicine) ,030211 gastroenterology & hepatology ,Life Sciences & Biomedicine ,Research Article ,EXPRESSION ,medicine.medical_specialty ,NAFLD, non-alcoholic fatty liver disease ,NASH, non-alcoholic steatohepatitis ,Population ,Gastroenterology and Hepatology ,SAF, steatosis–activity–fibrosis ,VALIDATION ,ER, endoplasmic reticulum ,03 medical and health sciences ,cDNA, complementary DNA ,Internal medicine ,ALT, alanine aminotransferase ,Gastroenterologi ,Internal Medicine ,medicine ,NAFL, non-alcoholic fatty liver ,ALGORITHM ,FIB-4, fibrosis-4 ,education ,030304 developmental biology ,PCA, principal component analysis ,Science & Technology ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,FC, fold change ,medicine.disease ,digestive system diseases ,FLIP, fatty liver inhibition of progression ,Ct, cycle threshold ,Steatosis ,qPCR, quantitative PCR ,business - 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. Lay summary MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy., Graphical abstract, Highlights • Serum miRNA was sequenced in 183 NAFLD cases of varying severity and 10 population controls. • Plasma levels of miR-193a-5p were significantly increased in patients with advanced fibrosis, high NAS scores, or high SAF scores. • Other miRNAs including miR378d and miR378e were also significantly increased in certain comparisons. • The findings for miR-193a-5p were replicated in a cohort of 372 additional NAFLD cases.
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- 2022
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12. Scientific Business Abstracts.
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Cooles F, Vidal-Pedrola G, Naamane N, Pratt A, Barron-Millar B, Anderson A, Hilkens C, Casement J, Bondet V, Duffy D, Zhang F, Shukla R, Isaacs J, Little M, Payne M, Coupe N, Fairfax B, Taylor CA, Mackay S, Milotay G, Bos S, Hunter B, Mcdonald D, Merces G, Sheldon G, Pradère P, Majo J, Pulle J, Vanstapel A, Vanaudenaerde BM, Vos R, Filby AJ, Fisher AJ, Collier J, Lambton J, Suomi F, Prigent M, Guissart C, Erskine D, Rozanska A, Mccorvie T, Trimouille A, Imam A, Hobson E, Mccullagh H, Frengen E, Misceo D, Bjerre A, Smeland M, Klingenberg C, Alkuraya F, Mcfarland R, Alston C, Yue W, Legouis R, Koenig M, Lako M, Mcwilliams T, Oláhová M, Taylor R, Newman W, Harkness R, McDermott J, Metcalfe K, Khan N, Macken W, Pitceathly R, Record C, Maroofian R, Sabir A, Santra S, Urquhart J, Demain L, Byers H, Beaman G, Yue W, Taylor R, Durmusalioglu E, Atik T, Isik E, Cogulu O, Reunert J, Marquardt T, Ryba L, Buchert-Lo R, Haack T, Lassuthova P, Polavarapu K, Lochmuller H, Horvath R, Jamieson P, Reilly M, O'Keefe R, Boggan R, Ng YS, Franklin I, Alston C, Blakely E, Büchner B, Bugiardini E, Colclough K, Feeney C, Hanna M, Hattersley A, Klopstock T, Kornblum C, Mancuso M, Patel K, Pitceathly R, Pizzamiglio C, Prokisch H, Schäfer J, Schaefer A, Shepherd M, Thaele A, Thomas R, Turnbull D, Gorman G, Woodward C, McFarland R, Taylor R, Cordell H, Pickett S, Tsilifis C, Pearce M, Gennery A, Daly A, Darlay R, Zatorska M, Worthington S, Anstee Q, Cordell H, Reeves H, Nizami S, Mauricio-Muir J, McCain M, Singh R, Wordsworth J, Kadharusman M, Watson R, Masson S, McPherson S, Burt A, Tiniakos D, Littler P, Nsengimana J, Zhang S, Mann D, Jamieson D, Leslie J, Shukla R, Wilson C, Betts J, Croall I, Hoggard N, Bennett J, Naamane N, Hollingsworth KG, Pratt AG, Egail M, Feeney C, Di Leo V, Taylor RW, Dodds R, Anderson AE, Sayer AA, Isaacs JD, McCracken C, Condurache DG, Szabo L, Elghazaly H, Walter F, Meade A, Chakraverty R, Harvey N, Manisty C, Petersen S, Neubauer S, Raisi-Estabragh Z, Allen L, Taylor P, Carlsson A, Hagopian W, Hedlund E, Hill A, Jones A, Ludvigsson J, Onengut-Gumuscu S, Redondo M, Rich S, Gillespie K, Dayan C, Oram R, Resteu A, Wonders K, Schattenberg J, Straub B, Ekstedt M, Berzigotti A, Geier A, Francque S, Driessen A, Boursier J, Yki-Jarvinen H, Arola J, Aithal G, Holleboom A, Verheij J, Yunis C, Trylesinski A, Papatheodoridis G, Petta S, Romero-Gomez M, Bugianesi E, Paradis V, Ratziu V, Tiniakos D, Anstee Q, Burton J, Ciminata G, Geue C, Quinn T, Glover E, Morais M, Reynolds G, Denby L, Ali S, Lennon R, Sheerin N, Yang F, Zounemat-Kermani N, Dixey P, Adcock IM, Bloom CI, Chung KF, Govaere O, Hasoon M, Alexander L, Cockell S, Tiniakos D, Ekstedt M, Schattenberg JM, Boursier J, Bugianesi E, Ratziu V, Daly AK, and Anstee QM
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- 2024
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13. The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease.
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Hardy T, Wonders K, Younes R, Aithal GP, Aller R, Allison M, Bedossa P, Betsou F, Boursier J, Brosnan MJ, Burt A, Cobbold J, Cortez-Pinto H, Day CP, Dufour JF, Ekstedt M, Francque S, Harrison S, Miele L, Nasr P, Papatheodoridis G, Petta S, Tiniakos D, Torstenson R, Valenti L, Holleboom AG, Yki-Jarvinen H, Geier A, Romero-Gomez M, Ratziu V, Bugianesi E, Schattenberg JM, and Anstee QM
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- Cohort Studies, Humans, Liver pathology, Liver Cirrhosis diagnosis, Liver Cirrhosis epidemiology, Liver Cirrhosis pathology, Longitudinal Studies, Registries, Diabetes Mellitus, Type 2, Liver Neoplasms pathology, Non-alcoholic Fatty Liver Disease diagnosis, Non-alcoholic Fatty Liver Disease epidemiology, Non-alcoholic Fatty Liver Disease therapy
- Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS 'Liver Investigation: Testing Marker Utility in Steatohepatitis' consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2020
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