Browsing by Author "Bugianesi, Elisabetta"

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    A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease
    (2022) Younossi, Zobair M.; Ong, Janus P.; Takahashi, Hirokazu; Yilmaz, Yusuf; Hi, Yuichiro Eguc; El Kassas, Mohamed; Buti, Maria; Diago, Moises; Zheng, Ming-Hua; Fan, Jian-Gao; Yu, Ming-Lung; Wong, Vincent Wai-Sun; Alswat, Khalid; Chan, Wah-Kheong; Mendez-Sanchez, Nahum; Burra, Patrizia; Bugianesi, Elisabetta; Duseja, Ajay K.; George, Jacob; Papatheodoridis, George, V; Saeed, Hamid; Castera, Laurent; Arrese, Marco; Kugelmas, Marcelo; Romero-Gomez, Manuel; Alqahtani, Saleh; Ziayee, Mariam; Lam, Brian; Younossi, Issah; Racila, Andrei; Henry, Linda; Stepanova, Maria
    BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally.
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Pablo Arab, Juan; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Castro Narro, Graciela E.; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Kowdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookoian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
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    A multisociety Delphi consensus statement on new fatty liver disease nomenclature
    (2023) Rinella, Mary E.; Lazarus, Jeffrey V.; Ratziu, Vlad; Francque, Sven M.; Sanyal, Arun J.; Kanwal, Fasiha; Romero, Diana; Abdelmalek, Manal F.; Anstee, Quentin M.; Arab, Juan Pablo; Arrese, Marco; Bataller, Ramon; Beuers, Ulrich; Boursier, Jerome; Bugianesi, Elisabetta; Byrne, Christopher D.; Narro, Graciela E. Castro; Chowdhury, Abhijit; Cortez-Pinto, Helena; Cryer, Donna R.; Cusi, Kenneth; El-Kassas, Mohamed; Klein, Samuel; Eskridge, Wayne; Fan, Jiangao; Gawrieh, Samer; Guy, Cynthia D.; Harrison, Stephen A.; Kim, Seung Up; Koot, Bart G.; Korenjak, Marko; Howdley, Kris V.; Lacaille, Florence; Loomba, Rohit; Mitchell-Thain, Robert; Morgan, Timothy R.; Powell, Elisabeth E.; Roden, Michael; Romero-Gomez, Manuel; Silva, Marcelo; Singh, Shivaram Prasad; Sookbian, Silvia C.; Spearman, C. Wendy; Tiniakos, Dina; Valenti, Luca; Vos, Miriam B.; Wong, Vincent Wai-Sun; Xanthakos, Stavra; Yilmaz, Yusuf; Younossi, Zobair; Hobbs, Ansley; Villota-Rivas, Marcela; Newsome, Philip N.
    The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steato-hepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/ wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.(c) 2023 American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Fundacion Clinica Medica Sur, A.C. Published by Wolters Kluwer/Elsevier B.V/ Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Consensus Statement on the definition and classification of metabolic hyperferritinaemia
    (2023) Valenti, Luca; Corradini, Elena; Adams, Leon A.; Aigner, Elmar; Alqahtani, Saleh; Arrese, Marco; Bardou-Jacquet, Edouard; Bugianesi, Elisabetta; Fernandez-Real, Jose-Manuel; Girelli, Domenico; Hagstrom, Hannes; Henninger, Benjamin; Kowdley, Kris; Ligabue, Guido; McClain, Donald; Laine, Fabrice; Miyanishi, Koji; Muckenthaler, Martina U.; Pagani, Alessia; Pedrotti, Patrizia; Pietrangelo, Antonello; Prati, Daniele; Ryan, John D.; Silvestri, Laura; Spearman, C. Wendy; Stal, Per; Tsochatzis, Emmanuel A.; Vinchi, Francesca; Zheng, Ming-Hua; Zoller, Heinz
    Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
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    Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients With Nonalcoholic and Alcohol-Related Fatty Liver Disease
    (2019) Younossi, Zobair M.; Stepanova, Maria; Ong, Janus; Yilmaz, Yusuf; Duseja, Ajay; Eguchi, Yuichiro; El Kassas, Mohamed; Castellanos-Fernandez, Marlen; George, Jacob; Jacobson, Ira M.; Bugianesi, Elisabetta; Wong, Vincent Wai-Sun; Arrese, Marco; de Ledinghen, Victor; Romero-Gomez, Manuel; Mendez-Sanchez, Nahum; Ahmed, Aijaz; Wong, Robert; Papatheodoridis, Georgios; Serfaty, Lawrence; Younossi, Issah; Nader, Fatema; Ziayee, Mariam; Afendy, Arian
    BACKGROUND & AIMS: Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver.
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    Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
    (2022) Martinez-Arranz, Ibon; Bruzzone, Chiara; Noureddin, Mazen; Gil-Redondo, Ruben; Minchole, Itziar; Bizkarguenaga, Maider; Arretxe, Enara; Iruarrizaga-Lejarreta, Marta; Fernandez-Ramos, David; Lopitz-Otsoa, Fernando; Mayo, Rebeca; Embade, Nieves; Newberry, Elizabeth; Mittendorf, Bettina; Izquierdo-Sanchez, Laura; Smid, Vaclav; Arnold, Jorge; Iruzubieta, Paula; Perez Castano, Ylenia; Krawczyk, Marcin; Marigorta, Urko M.; Morrison, Martine C.; Kleemann, Robert; Martin-Duce, Antonio; Hayardeny, Liat; Vitek, Libor; Bruha, Radan; Aller de la Fuente, Rocio; Crespo, Javier; Romero-Gomez, Manuel; Banales, Jesus M.; Arrese, Marco; Cusi, Kenneth; Bugianesi, Elisabetta; Klein, Samuel; Lu, Shelly C.; Anstee, Quentin M.; Millet, Oscar; Davidson, Nicholas O.; Alonso, Cristina; Mato, Jose M.
    Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.
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    Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice
    (2023) 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; Hagstrom, Hannes; Loomba, Rohit; Romero-Gomez, Manuel; Schattenberg, Jorn M.; Thiele, Maja; Valenti, Luca; Wong, Vincent Wai-Sun; Yilmaz, Yusuf; Younossi, Zobair M.; Francque, Sven M.; Tsochatzis, Emmanuel A.
    Background & Aims: Non-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. Methods: A 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.Results: There 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 & REG;), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan & REG;, 21% of respondents used a single liver stiffness cut-off: 8 kPa in 50%, while the rest used 7.2 kPa, 7.8 kPa and 8.7 kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10 kPa and >7.5 to >20 kPa, respectively).Conclusions: The 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 summary: Owing 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.& COPY; 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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    The macrophage activation marker sCD163 is associated with morphological disease stages in patients with non-alcoholic fatty liver disease
    (2016) Kazankov, Konstantin; Barrera Martínez, Francisco; Møller, Holger Jon; Rosso, Chiara; Bugianesi, Elisabetta; David, Ezio; Jouness, Ramy; Esmaili, Saeed; Eslam, A. Mohammed; McLeod, Duncan