From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a prevalent chronic liver disease worldwide, affecting more than 30% of the global population (1Rinella M.E. Neuschwander-Tetri B.A. Siddiqui M.S. Abdelmalek M.F. Caldwell S. Barb D. Kleiner D.E. Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.Hepatology. 2023; 77: 1797-1835Crossref PubMed Scopus (173) Google Scholar, 2Yip T.C. Vilar-Gomez E. Petta S. Yilmaz Y. Wong G.L. Adams L.A. de L.,V. Sookoian S. Wong V.W. Geographical similarity and differences in the burden and genetic predisposition of NAFLD.Hepatology. 2023; 77: 1404-1427Crossref PubMed Scopus (26) Google Scholar). Importantly, MASLD is a multifaceted disorder resulting from complex interactions with various cardiometabolic and environmental risk factors (3Loomba R. Friedman S.L. Shulman G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease.Cell. 2021; 184: 2537-2564Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar, 4Powell E.E. Wong V.W. Rinella M. Non-alcoholic fatty liver disease.Lancet. 2021; 397: 2212-2224Abstract Full Text Full Text PDF PubMed Scopus (798) Google Scholar, 5Sookoian S. Pirola C.J. How Safe Is Moderate Alcohol Consumption in Overweight and Obese Individuals?.Gastroenterology. 2016; 150: 1698-1703Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Non-alcoholic steatohepatitis (NASH), now replaced with the term metabolic dysfunction-associated steatohepatitis (MASH), was initially coined in 1980 to denote a condition exhibiting the histological traits of alcohol associated liver disease in individuals who neither consume alcohol nor have any other liver disease of clinical importance (6Eslam M. Sanyal A.J. George J. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease.Gastroenterology. 2020; 158: 1999-2014Abstract Full Text Full Text PDF PubMed Google Scholar, 7Ludwig J. Viggiano T.R. McGill D.B. Oh B.J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.Mayo Clin. Proc. 1980; 55: 434-438PubMed Google Scholar). Since then, there has been a surge in interest around MASLD, primarily due to its rapidly escalating global prevalence and the consequent research into its pathophysiological, clinical, and socioeconomic implications. Today, with advances in our understanding of disease pathophysiology, it is clear that while there is a clear underpinning of insulin resistance and adipose tissue dysfunction, significant heterogeneity exists, characterized by varying rates of progression and varied response to treatment (8Arrese M. Arab J.P. Barrera F. Kaufmann B. Valenti L. Feldstein A.E. Insights into Nonalcoholic Fatty-Liver Disease Heterogeneity.Semin Liver Dis. 2021; 41: 421-434Crossref PubMed Scopus (48) Google Scholar, 9Pirola C.J. Sookoian S. Advances in our understanding of the molecular heterogeneity of fatty liver disease: toward informed treatment decision making.Expert. Rev. Gastroenterol. Hepatol. 2023; 17: 317-324Crossref Scopus (2) Google Scholar). These outcomes can be influenced by physiological, environmental factors alongside genetic predisposition (10Sookoian S. Pirola C.J. Valenti L. Davidson N.O. Genetic Pathways in Nonalcoholic Fatty Liver Disease: Insights From Systems Biology.Hepatology. 2020; 72: 330-346Crossref PubMed Scopus (63) Google Scholar). Advances in disease pathogenesis provide insight into potentially viable treatment targets, currently under clinical development (11Friedman S.L. Neuschwander-Tetri B.A. Rinella M. Sanyal A.J. Mechanisms of NAFLD development and therapeutic strategies.Nat. Med. 2018; 24: 908-922Crossref PubMed Scopus (2050) Google Scholar, 12Pirola C.J. Sookoian S. The lipidome in nonalcoholic fatty liver disease: actionable targets.J. Lipid Res. 2021; 62100073Abstract Full Text Full Text PDF PubMed Google Scholar) and reliable disease biomarkers (13Wong V.W. Adams L.A. de L., V, Wong, G.L. Sookoian S. Noninvasive biomarkers in NAFLD and N.Nat. Rev. Gastroenterol. Hepatol. 2018; 15: 461-478Crossref PubMed Scopus (0) Google Scholar). Nonetheless, despite these advances in our understanding of dominant driving factors, the name of the disease remained unchanged from when it was first introduced 40 years ago. It was crucial for the global liver community to adopt a revised nomenclature that acknowledged the root cause of disease and provide diagnostic criteria, while using non-stigmatizing language. The Nomenclature Development Initiative's global members' main objective was to establish revised nomenclature that could be implemented worldwide, raise disease awareness, and direct research and funding to save more lives (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar). While the term "nonalcoholic" is commonly used, it has been acknowledged that it does not accurately reflect the current understanding of disease drivers. Enough knowledge exists about the pathophysiology of NAFLD to move from a diagnosis of exclusion to one defined by specific criteria. Further, the terminology was considered stigmatizing to some and potentially disparaging to those who suffer with alcohol associated/related liver disease. Additionally, the terminology "fatty" to describe a medical condition can be stigmatizing for some patients. As part of the Delphi process undertaken to reconsider NAFLD nomenclature, 61% and 66% of respondents found the terms 'non-alcoholic' and 'fatty' potentially stigmatizing (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar), respectively. While the extent of perceived stigma will vary across individuals and cultures and thus highly dependent on who is asked and how they are asked the question, it is clear that if the use of stigmatizing language can be avoided, it should, since no level of stigma should be deemed 'acceptable' (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. 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Alcohol intake is common in many cultures, and this left many patients outside of the NAFLD diagnostic category, which limits daily intake to <20g/30g for females and males, respectively. Such patients were explicitly excluded from therapeutic trials and biomarker consortia, despite being at higher risk for adverse liver related outcomes and all-cause mortality (1Rinella M.E. Neuschwander-Tetri B.A. Siddiqui M.S. Abdelmalek M.F. Caldwell S. Barb D. Kleiner D.E. Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.Hepatology. 2023; 77: 1797-1835Crossref PubMed Scopus (173) Google Scholar, 18Rasmussen D.G.K. Anstee Q.M. Torstenson R. Golding B. Patterson S.D. Brass C. Thakker P. Harrison S. Billin A.N. Schuppan D. Dufour J.F. Andersson A. Wigley I. Shumbayawonda E. Dennis A. Schoelch C. Ratziu V. Yunis C. Bossuyt P. Karsdal M.A. NAFLD and NASH biomarker qualification in the LITMUS consortium - Lessons learned.J. Hepatol. 2023; 78: 852-865Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 19Sanyal A.J. Shankar S.S. Calle R.A. Samir A.E. Sirlin C.B. Sherlock S.P. Loomba R. Fowler K.J. Dehn C.A. Heymann H. Kamphaus T.N. Non-Invasive Biomarkers of Nonalcoholic Steatohepatitis: the FNIH NIMBLE project.Nat. Med. 2022; 28: 430-432Crossref PubMed Scopus (22) Google Scholar). Furthermore, there is a growing recognition that there are overlapping biological processes that may contribute to both NAFLD and alcohol-related liver disease (ALD) (20Aberg F. Byrne C.D. Pirola C.J. Mannisto V. Sookoian S. Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease.J. Hepatol. 2023; 78: 191-206Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar). NAFLD was an overarching term that encompassed numerous causes of steatosis, though what was managed as NAFLD/NASH represented a fairly specific disease entity characterized by the presence of cardiometabolic risk factors (CMRFs). Thus, the revised nomenclature selected an overarching term of steatotic liver disease (SLD) to parse out MASLD (what was considered true 'NAFLD') from other causes of steatosis, e.g. hypobetalipoproteinemia, celiac disease etc., as well as mixed etiology conditions, such as overlap with alcohol, and alcohol associated liver disease as well (Figure 1). The desire to address the limitations of the existing nomenclature of NAFLD led to the development of a global collaborative multi-stakeholder effort under the leadership of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) in conjunction with the Asociación Latinoamericana para el Estudio del Hígado (ALEH) and other organizations (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar). Experts from diverse fields, including hepatology, gastroenterology, pediatrics, endocrinology, hepatopathology, public health, and obesity, partnered with colleagues from industry, regulatory agencies, and patient advocacy organizations to develop questions to be addressed by the full member panel. The process was guided by a group deeply rooted in Delphi methodology (19Sanyal A.J. Shankar S.S. Calle R.A. Samir A.E. Sirlin C.B. Sherlock S.P. Loomba R. Fowler K.J. Dehn C.A. Heymann H. Kamphaus T.N. Non-Invasive Biomarkers of Nonalcoholic Steatohepatitis: the FNIH NIMBLE project.Nat. Med. 2022; 28: 430-432Crossref PubMed Scopus (22) Google Scholar, 21Lazarus J.V. Romero D. Kopka C.J. Karim S.A. Abu-Raddad L.J. Almeida G. Baptista-Leite R. Barocas J.A. Barreto M.L. Bar-Yam Y. Bassat Q. Batista C. Bazilian M. Chiou S.T. Del R.C. Dore G.J. Gao G.F. Gostin L.O. Hellard M. Jimenez J.L. Kang G. Lee N. Maticic M. McKee M. Nsanzimana S. Oliu-Barton M. Pradelski B. Pyzik O. Rabin K. Raina S. Rashid S.F. Rathe M. Saenz R. Singh S. Trock-Hempler M. Villapol S. Yap P. Binagwaho A. Kamarulzaman A. El-Mohandes A. A multinational Delphi consensus to end the COVID-19 public health threat.Nature. 2022; 611: 332-345Crossref PubMed Scopus (67) Google Scholar). They worked together to develop a consensus on revisions to the nomenclature and diagnostic criteria for this condition. The 33-member steering committee developed a 4-part Delphi survey, in combination with 2 large in person meetings to discuss points of controversy across a 3-year period. Members of the full Delphi panel represented 56 countries and spanned several relevant sectors, as previously noted. The committee identified five essential areas to consider when revising nomenclature: (1Rinella M.E. Neuschwander-Tetri B.A. Siddiqui M.S. Abdelmalek M.F. Caldwell S. Barb D. Kleiner D.E. Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.Hepatology. 2023; 77: 1797-1835Crossref PubMed Scopus (173) Google Scholar) Can shortcomings of the current nomenclature be addressed? (2Yip T.C. Vilar-Gomez E. Petta S. Yilmaz Y. Wong G.L. Adams L.A. de L.,V. Sookoian S. Wong V.W. Geographical similarity and differences in the burden and genetic predisposition of NAFLD.Hepatology. 2023; 77: 1404-1427Crossref PubMed Scopus (26) Google Scholar) How important is steatohepatitis in disease definitions and endpoints? (3Loomba R. Friedman S.L. Shulman G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease.Cell. 2021; 184: 2537-2564Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar) How should the role of alcohol role be considered? (4Powell E.E. Wong V.W. Rinella M. Non-alcoholic fatty liver disease.Lancet. 2021; 397: 2212-2224Abstract Full Text Full Text PDF PubMed Scopus (798) Google Scholar) How would renaming affect disease awareness, clinical trials, and regulatory approval processes? (5Sookoian S. Pirola C.J. How Safe Is Moderate Alcohol Consumption in Overweight and Obese Individuals?.Gastroenterology. 2016; 150: 1698-1703Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar) Can a new name decrease heterogeneity and facilitate future advancements? (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar). The Delphi panel defined a priori the consensus threshold of a ≥67% supermajority, except for two instances; considering the presence of stigma (for reasons noted above) and deciding whether to retain or change the current definition, once a supermajority had decided to revise the nomenclature, since it would have been illogical to re-define using affirmative language without providing criteria to diagnose it. The priorities in outlining the diagnostic criteria were to err on the side of being inclusive, to avoid large numbers of uncategorized patients and thus to assure that decades of natural history studies in NAFLD or those in biomarker registries, would refer to the same population (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar). Since the publication of the nomenclature consensus document, comparative studies in various settings, including registries, population studies, community cohorts and primary care settings have noted near complete capture of the prior NAFLD population, using the definition for MASLD (22Ratziu V. Boursier J. Confirmatory biomarker diagnostic studies are not needed when transitioning from NAFLD to MASLD.J. Hepatol. 2023; Abstract Full Text Full Text PDF Scopus (3) Google Scholar, 23Song S.J. Lai J.C. Wong G.L. Wong V.W. Yip T.C. Can we use old NAFLD data under the new MASLD definition?.J. Hepatol. 2023; Abstract Full Text Full Text PDF Scopus (15) Google Scholar, 24Lee C. Yoon E. Kim M. Kang B. Cho S. Nah E. Jun D. Prevalence, distribution and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.Hepatology. 2023; https://doi.org/10.1097/HEP.0000000000000664Crossref Google Scholar). The consensus was to change the definition of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD), which now requires the presence of at least one of five cardiometabolic risk factors in the context of hepatic steatosis (Figure 1). The caveat exists, as it did for NAFLD in the setting of advanced fibrosis, where steatosis may no longer be present (14Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Narro G.E.C. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Ann. Hepatol. 2023; 29101133Google Scholar, 15Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J. Hepatol. 2023; Google Scholar, 16Rinella M.E. Lazarus J.V. Ratziu V. Francque S.M. Sanyal A.J. Kanwal F. Romero D. Abdelmalek M.F. Anstee Q.M. Arab J.P. Arrese M. Bataller R. Beuers U. Boursier J. Bugianesi E. Byrne C.D. Castro Narro G.E. Chowdhury A. Cortez-Pinto H. Cryer D.R. Cusi K. El-Kassas M. Klein S. Eskridge W. Fan J. Gawrieh S. Guy C.D. Harrison S.A. Kim S.U. Koot B.G. Korenjak M. Kowdley K.V. Lacaille F. Loomba R. Mitchell-Thain R. Morgan T.R. Powell E.E. Roden M. Romero-Gomez M. Silva M. Singh S.P. Sookoian S.C. Spearman C.W. Tiniakos D. Valenti L. Vos M.B. Wong V.W. Xanthakos S. Yilmaz Y. Younossi Z. Hobbs A. Villota-Rivas M. Newsome P.N. A multisociety Delphi consensus statement on new fatty liver disease nomenclature.Hepatology. 2023; 78: 1966-1986Crossref PubMed Scopus (0) Google Scholar). Steatotic liver disease (SLD) was chosen as the overarching term to encompass the various causes of steatosis. The term cryptogenic SLD was reserved for those not meeting criteria for MASLD or a specific alternative etiology, acknowledging that such patients may be re-classified in the future as more data emerge. The new names to not alter the characterization of fibrotic severity or alter the definition of steatohepatitis, thus MASH can replace NASH. While not the intent of the nomenclature process, it is noted that in the future, staging may not be limited to histology, rather it will likely evolve to non-invasive staging of disease. Thus, the current consensus process adheres to previous case definitions for steatohepatitis and disease stages. The diagnosis of MASLD/MASH with advanced fibrosis or cirrhosis, even when steatosis is absent, will be based on previously agreed-upon criteria for NASH cirrhosis. This also applies to patients with MetALD and ALD (Figure) with significant fibrosis who may not have steatosis but still have SLD as part of the overall nomenclature, reflecting the injury mechanism. The new nomenclature enhances the previous "nonalcoholic" label and accurately connects this liver disease to metabolic factors, previously referred to as "the hepatic manifestation of the metabolic syndrome." This fundamental conceptual shift brings numerous practical implications. When discussing the disease with patients, it is advantageous to present a clear and concise explanation based on the underlying cardiometabolic irregularities that are associated with insulin resistance and the patient's other conditions. This approach is more straightforward than using a diagnosis of exclusion and makes it easier for patients to comprehend. Additionally, it aids in communicating the primary therapeutic steps to be taken, as well as the risk factors for disease progression, both from a liver-oriented and holistic standpoint. It has been difficult to identify a suitable replacement that satisfies the required criteria. Finding a term that fully encompasses the intricacy of the disease has proven to be a challenge. Yet, it was demonstrated that MASLD overlaps almost entirely with the NAFLD population (22Ratziu V. Boursier J. Confirmatory biomarker diagnostic studies are not needed when transitioning from NAFLD to MASLD.J. Hepatol. 2023; Abstract Full Text Full Text PDF Scopus (3) Google Scholar, 23Song S.J. Lai J.C. Wong G.L. Wong V.W. Yip T.C. Can we use old NAFLD data under the new MASLD definition?.J. Hepatol. 2023; Abstract Full Text Full Text PDF Scopus (15) Google Scholar). The new structure should allow for incorporation of emergent phenotypes as the field progresses. Despite decades of research and the promise of future therapeutics, awareness of NAFLD has remained low. This can be attributed to several factors, including low provider awareness of which patients are at risk of disease progression and identification of those with established advanced disease and a misperception that fatty liver is a benign entity. This then translates to patients understanding that it is not a major concern. 'Re-branding' using terminology that links to disease underpinnings offers the opportunity to highlight impactful interventions. The likely emergence in the near-term of the first FDA approved treatment for NASH/MASH has heightened efforts to identify patients at risk for progression who may be eligible for treatment, which can and will be leveraged to increase awareness of the new nomenclature by fostering collaborative efforts between society and industry. Dissemination of the new nomenclature within and outside of Hepatology is critical, as is adoption by journals and medical societies. Thus far, the new nomenclature has been endorsed by over 75 societies, only months after publication. Work is underway to begin to incorporate changes into medical school curricula and other areas of medical education. The biggest barrier to full implementation is the time and effort required to change billing codes, for which national, as well as international efforts have begun. Based on the above considerations, we encourage authors of papers who are planning to submit to the Journal of Lipid Research to use the updated nomenclature and specifically where human subjects are involved. Authors of papers reporting findings in preclinical and cell-based models of steatosis/inflammatory responses are encouraged to use the term steatotic rather than 'fatty' in their qualitative descriptions. MER: Scientific consulting for Boehringer Ingelheim, Cytodyn, Histoindex, Intercept, GSK, Madrigal, Novo Nordisk and Takeda over the past 24 months. No speakers' bureaus or stock ownership. SS: No potential conflicts of interest.