Unified global approaches to nomenclature and disease definition are critical for increasing disease awareness, driving policy change, identifying those at risk, and facilitating diagnosis and access to care. Language can create or exacerbate stigma, marginalise segments of the affected population, and, ultimately, contribute to health inequalities. It has been known for many years that being overweight or obese is associated with hepatic steatosis, hepatocyte injury, liver inflammation, and fibrosis. This was formally recognised by the term “nonalcoholic steatohepatitis” in 1980 by Jurgen Ludwig [1]. Subsequently, the term nonalcoholic fatty liver disease (NAFLD) was used to describe the histological spectrum of steatosis to steatohepatitis with its subtypes NAFL and NASH. The histological classification was further expanded on by various scoring systems categorising steatosis, disease activity, and fibrosis [2–4]. This framework has served as the anchor for our current understanding of the disease, data on the burden of the disease, and efforts to develop a treatment for the condition.

While the nomenclature is widely used, it has always been appreciated that the term “nonalcoholic” did not accurately capture what the aetiology of the disease was, and notably, the term “fatty” has been considered to be stigmatising by some. Furthermore, there are individuals with risk factors for NAFLD, such as type 2 diabetes, who consume more alcohol than the relatively strict thresholds used to define the nonalcoholic nature of the disease, which are not adequately recognised by existing nomenclature and are excluded from trials and consideration for treatments [5]. Indeed, there is a recognition now that there are overlapping biological processes that may contribute to both NAFLD and alcohol-associated/related liver disease (ALD). All of these factors have led to growing dissatisfaction with the current nomenclature. This was summarised in a paper by Eslam et al., [6,7] in 2020 and led to the proposal to use the term metabolic dysfunction–associated fatty liver disease (MAFLD), which includes patients with a fatty liver regardless of the amount and pattern of alcohol intake under this terminology. While MAFLD was accepted by some, concerns were raised about the mixing of etiologies, continued use of the term “fatty” considered stigmatising by many, and restricting the population to those with 2 metabolic risk factors and allowance of more liberal alcohol use, thus impacting our understanding of natural history [8–10]. One area of particular concern was the potential negative impact of changes in diagnostic criteria for the disease in terms of biomarker and therapeutic development [7,9,10].

These concerns led to a multistakeholder effort under the auspices of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) in collaboration with the Asociación Latinoamericana para el Estudio del Hígado (ALEH) with the engagement of academic professionals from around the world, including hepatologists, gastroenterologists, pediatricians, endocrinologists, hepatopathologists, and public health and obesity experts along with colleagues from industry, regulatory agencies, and patient advocacy organisations to resolve these concerns and develop a consensus on a change in nomenclature and the diagnostic criteria for the condition. This manuscript summarises the methodology, including a multistep Delphi process, the results of the process and provides the consensus recommendations endorsed by societies, patient advocacy groups, journals, and industry for adoption by all stakeholders.

Identification of a new name and definition for the condition formerly known as NAFLD has been a challenging process given the broad range of global stakeholders. It is imperative that any new proposal is sufficiently better than the existing nomenclature, and it enhances awareness, understanding of the disease, without negatively impacting drug/biomarker development. This robust, representative, patient-centric Delphi process systematically addressed all the issues and views over the past years and, through consensus, has arrived at both a new name and a refined definition. By inclusion of patient advocacy groups throughout the entire process, the new nomenclature strives to accelerate disease awareness while minimising stigma associated with the use of terms perceived as stigmatising by some patients and their caregivers.

Several important findings emerged from the nomenclature consensus process; there was clear support for a name change, the use of an overarching term that could accommodate the evolution of disease understanding, and the use of a metabolic descriptor in the new nomenclature. Both the overarching term of SLD and the more specific MASLD provide an affirmative nonstigmatising description of the condition rather than a diagnosis of exclusion. This is also seen in the definition, which requires the presence of at least 1 CMRF in addition to hepatic steatosis. The proposed nomenclature is not intended to be static but rather allows the flexibility for refinement as new evidence emerges about underlying pathophysiology and risk factors.

A key consideration is the preservation of existing data on natural history, biomarkers, and clinical trials as part of these changes. To address the impact of the refined definition, an analysis of the LITMUS consortium European was performed, which demonstrated that 98% of the existing registry cohort of patients with NAFLD would fulfill the new criteria for MASLD [19]. Conceptually patients with the previous definition (NAFLD) can now be seen to be completely covered by the categories of MASLD and possible MASLD. The introduction of a separate MetALD subcategory where metabolic and alcohol-associated risk factors coexist sits outside MASLD/NAFLD and is an opportunity to generate new knowledge for this common group of patients. In addition, maintenance of the term, and clinical definition, of steatohepatitis ensures retention and validity of prior data from clinical trials and biomarker discovery studies of patients with NASH to be generalisable to individuals classified as MASLD or MASH under the new nomenclature, without impeding the efficiency of research.

The Delphi process utilised a supermajority threshold of 67% with 2 exceptions, the consideration of stigma, and a binary question to retain or revise the current definition. While recognising that perceptions of stigma differ widely [20,21], especially across different languages and cultures, in this study, it became clear that substantial proportions of the respondents deemed terms such as “fatty” stigmatising, hence its exclusion as part of any new name. Although healthcare professionals may contend that patients have not reported this previously, this likely reflects in part a failure to ask the question in the first place and the power imbalance in the doctor-patient relationship. Moreover, a recent large study indicated that some healthcare professionals and patients considered the terms fatty and nonalcoholic to be pejorative and stigmatising [21]. The use of medical terminology such as steatosis may at one level be seen as overmedicalising the lexicon, yet it affords patients the opportunity to disclose their condition to friends and colleagues without having to face prejudice and stigma that can be inherent to the word “fatty.” [21,22] Efforts to increase disease awareness have had modest success, possibly impacted by the perception that care providers deem the term “fatty liver” as describing an indolent condition. With therapeutics on the horison, there is renewed energy to identify “at-risk” patients, which, in conjunction with new terminology, may bolster awareness and a sense of importance.

The overarching term of SLD encompasses the spectrum of causes of hepatic steatosis, thus allowing precise classification once a specific aetiology has been identified. The new names also allow for further characterisation of fibrotic severity, for example, MASH with stage 3 fibrosis. Disease staging and severity are not altered by this process although it is anticipated that, in the near to medium term, disease staging will be achieved using noninvasive tests, which can be incorporated into further clarifications of disease stage. Thus, the current consensus process does not deviate from prior case definitions for steatohepatitis and disease stages [23]. The diagnosis of MASLD/MASH with advanced fibrosis or cirrhosis, when steatosis may not be present, will be based on existing agreed criteria for NASH cirrhosis [23]. This also applies to patients with MetALD and ALD with significant fibrosis who may not have steatosis yet have SLD as part of the overarching nomenclature, reflecting the mechanism of injury.

The proposed nomenclature also improves on the prior “nonalcoholic” label and appropriately assigns a metabolic basis for this liver disease, which was long recognised as “the hepatic manifestation of the metabolic syndrome.” [5] This important conceptual change has several practical consequences. First, when addressing patients, it allows for a coherent and straightforward explanation of the disease as it is intuitively easier to understand in the context of its underlying cardiometabolic abnormalities linked to insulin resistance and its association with the patient's other conditions, rather than in the framework of a diagnosis of exclusion. This also helps to communicate to the patient the main therapeutic actions to be taken both from a liver and a holistic perspective. Second, we believe that using this classification will enhance disease awareness since the alignment of the diagnostic criteria for MASLD with widely recognised phenotypic traits in diabetes and cardiovascular medicine will make it easier for the larger community of health care providers to identify individuals with this condition. There is a strong convergence between the metabolic set of criteria that we propose for diagnosing MASLD and those proposed by Eslam et al.,[24] for MAFLD. However, the current consensus approach decided to prioritise robust and easily accessible clinical criteria and biological measurements, and as such, these criteria do not include direct measurements of insulin resistance (such as fasting insulin or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)) because of their complexity, cost, and variability between laboratories. However, in patients with hepatic steatosis in the absence of overt CMRFs, secondary testing for insulin resistance may be useful to identify those with possible MASLD. It is important to understand that the set of diagnostic criteria for MASLD is not intended to diagnose “metabolic syndrome” or predict the occurrence of cardiovascular outcomes. The CMRFs are intended to identify patients likely to have insulin resistance as the main cause of hepatic steatosis. There was consideration of providing differential weighting for the CMRFs, such as type 2 diabetes, although the literature is conflicting in that regard with some indicating that no parameter is better than another at identifying hepatic steatosis [25].

This process focuses on the nomenclature and definition of NAFLD rather than a determination of what constitutes hepatic steatosis or assessment of disease severity. There is extensive literature on the confirmation of hepatic steatosis [26,27], which we did not seek to interrogate; often, this is a pragmatic determination in clinical practice, which is where this guidance starts. Moreover, this nomenclature process, in line with published guidance [21,28,29], is not advocating for the routine use of tests to confirm hepatic steatosis although, in reality, most, if not all, patients will usually have imaging at some point. Finally, we recognise it is the evaluation of fibrosis either as part of screening strategies or individual clinical decisions, which is relevant for most clinical settings [30], That remains unchanged after this process, other than the name (e.g., MASLD with advanced fibrosis).

Contrary to the initial proposal by Eslam and colleagues, the Delphi process revealed that most experts consider that MetALD patients should be classified in a category distinct from MASLD, mainly because of the added pathogenic value of alcohol consumption and consequential prognostic implications. The condition MetALD provides an opportunity to better define the natural history of such patients and the development of biomarkers and therapies that are currently lacking for this group of patients [31]. ALD is a distinct liver disease (of which steatosis is one of the features) and, thus, is categorised under the SLD umbrella. This should raise awareness of alcohol as a driver of steatosis and highlight the impact of excessive alcohol consumption (i.e., >50–60 g daily in females and males, respectively) irrespective of their association with metabolic dysfunction. Studies have shown that, even in excessive drinkers, obesity increases the prevalence of cirrhosis, and glycaemic dysregulation increases fibrosis severity [32,33]. Patterns of alcohol use must also be taken into consideration as bingeing (even within the total weekly “allowable limit” for MASLD) can be detrimental. We also recognise that objective tools are not available or sufficiently validated to determine the relative contribution of MASLD and ALD in patients with MetALD, and hence, we rely on self-reported alcohol intake, which can be inaccurate. In that regard, this is a conceptual construct and might be better seen as a disease spectrum with differing of modifiable disease drivers (CMRFs and alcohol). This is also relevant for the distinction between patients with MetALD and those drinking more heavily, which are termed as having ALD. Also, the category of ALD without metabolic factors is relatively rare among patients with significant fibrosis, but it was felt to represent part of the spectrum.

In addition to defining a distinct category for patients with MASLD and greater alcohol consumption (MetALD), the proposed nomenclature allows, by introducing the umbrella term of SLD, for diagnostic subgroups of SLD to be identified, namely, those that are drug-related and others. The latter encompasses the many “secondary” causes of NAFLD, most of which are rare diseases, including monogenic diseases [31]. This is particularly relevant in children, in whom rare genetic metabolism defects can cause steatosis and must be considered [17]. Patients with steatosis without overt CMRFs or other discernible causes are labeled as cryptogenic although, depending on clinical judgment, they could also be deemed to have possible MASLD and would benefit from periodic reassessment on a case-by-case basis. Of note, genetic variants influencing the prevalence and/or severity of MASLD such as PNPLA3, TM6SF2, and HSD17B13, and other genetic risk variants that are common in the general population were not considered a distinct nosological entity. This was because these variants are disease modifiers for both MASLD and ALD rather than causative factors, in contrast to rare variants responsible for monogenic diseases. The change in nomenclature in favor of a positive diagnosis based on the presence of CMRFs will also allow for a rational reclassification of most cases of the condition formerly known as “lean NASH” into the regular MASLD category, as long as the currently defined metabolic risk factors are present. The “cryptogenic” category will, as mentioned, also accommodate the rare specific causes of SLD unrelated to metabolic dysfunction, alcohol consumption, drug intake, or other causes [34] while waiting for precise identification of the causal agent by future research.

Despite the many strengths of this rigorous process, we acknowledge limitations. The individual statements changed between R1 and R3 (Table S1,), and there was variation in levels of agreement for individual statements although this reflects their evolution, as important issues arose, which we needed to consider regarding the NAFLD nomenclature. Furthermore, the lack of uniform agreement on many topics reflects the diversity of opinions involved in the process. A priori, we chose a threshold of 67% (supermajority) to define consensus, which meant that some opinions, although held by a simple majority (>50% but <67%), did not influence the final decisions, with the exception of stigma and the decision to alter the disease definition. Nonetheless, we are confident that statements supported by a supermajority were addressed and incorporated.

In conclusion, we believe that this process, which has multistakeholder endorsement, provides a strong platform from which we can increase disease awareness, reduce stigma, and accelerate drug and biomarker development for the benefit of patients with MASLD, MASH, and MetALD.

American Association of Clinical Endocrinology, American College of Gastroenterology, American Gastroenterological Association, American Liver Foundation, American Society for Gastrointestinal Endoscopy, American Society for Preventive Cardiology, Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Asociación Chilena de Hepatología ACHHEP, Asociación Colombiana de Hepatología, Asociación de Especialistas en Gastroenterología y Endoscopia Digestiva de Costa Rica, Asociación Española para el Estudio del Hígado, Asociación Guatemalteca de Gastroenterología, Hepatología y Endoscopía Gastrointestinal, Asociación Mexicana de Hepatología, Asociación Peruana para el Estudio del Hígado, Asociación Puertorriqueña de Gastroenterología, Associação Portuguesa Para o Estudo do Fígado, Association Française pour l'Etude du Foie, Association of Black Gastroenterologists and Hepatologists, Association of Pakistani-Descent Gastroenterologists of North America (APGNA), Associazione Italiana per lo Studio del Fegato, Azerbaijan Gastroenterologists and Hepatologists Association, Banner Liver Support Group, Belgian Week of Gastroenterology, British Association for the Study of the Liver, British Liver Trust, British Society of Gastroenterology, Canadian Association for the Study of the Liver, Croatian Society of Gastroenterology, Danish Society for Gastroenterology and Hepatology, Deutsche Gesellschaft für Gastroenterologie, Verdauungsund Stoffwechselkrankheiten, European Liver Patient Association, European Society for Paediatric Gastroenterology, Hepatology, and Nutrition, Facebook Cirrhosis Support Group, Fatty Liver Foundation, Fatty Liver Study Foundation in Middle East and North Africa, Federation of the International Societies for Paediatric Gastroenterology, Hepatology, and Nutrition, Global Liver Institute, Hannover Medical School, Hellenic Association for the Study of the Liver, Indian National Association for Study of the Liver, Japan Society of Hepatology, Japan Study Group of NAFLD, Korean NAFLD Study Group, Latin American Society of Pediatric Gastroenterology, Hepatology, and Nutrition, Leverforeningen Danmark, Liver Patients International, Mexican Association of Gastroenterology, North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition, Norwegian Gastroenterology Society, Österreichische Gesellschaft für Gastroenterologie und Hepatologie, Pakistan Society of Hepatology, Polish Association for the Study of Liver, Romanian Society of Gastroenterology and Hepatology, Sociedad Argentina de Hepatología, Sociedad Cubana de Gastroenterología, Sociedad de Gastroenterología del Uruguay, Sociedad Dominicana de Gastroenterologia, Sociedad Española de Patología Digestiva, Sociedad Paraguaya de Diabetologia, Sociedad Venezolana de Gastroenterologia, Sociedade Brasileira de Hepatologia, Society of Gastroenterology and Hepatology of the Republic of Moldova, Society of Liver Disease in Africa, South Asian Association for Study of the Liver, Swedish Society of Gastroenterology, Swiss Association for the Study of the Liver, The Liver Forum, Turkish Association for the Study of the Liver, Ukrainian Association for the Study of Liver Diseases, United European Gastroenterology, Zambia Association of Gastroenterology and Nutrition.

AASLD, American Association for the Study of Liver Diseases; ALD, alcohol-associated/related liver disease; ALEH, Asociación Latinoamericana para el Estudio del Hígado (Latin American Association for the Study of the Liver); AMAGE, African Middle East Association of Gastroenterology; APASL, Asian Pacific Association for the Study of the Liver; BMI, body mass index; BP, blood pressure; CMRF, cardiometabolic risk factor; DILI, drug-induced liver disease; EASL, European Association for the Study of the Liver; GI, gastrointestinal; INASL, Indian National Association for the Study of the Liver; LALD, lysosomal acid lipase deficiency; MAFLD, metabolic dysfunction-associated fatty liver disease; MAS, metabolic dysfunction associated steatosis; MAASLD, metabolic dysfunction and alcohol associated steatotic liver disease; MASH, metabolic dysfunction -associated steatohepatitis; MASLD, metabolic dysfunction associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol associated steatotic liver disease; MetSLD, metabolic dysfunction associated steatotic liver disease; MHS, metabolic hepatic steatosis; MSLD, metabolic steatotic liver disease; RR, response rate; SAASL, South Asian Association for the Study of the Liver; SLD, steatotic liver disease; TASL, Taiwan Association for the Study of the Liver; WC, waist circumference.