Researchers call for more flexible editorial conduct rather than abruptly adopting only the new MASLD nomenclature
Authors: Amedeo Lonardo, Fernando Bril, Stephen H. Caldwell, Mohammed Eslam, Jian-Gao Fan, Robert G. Gish, Henning Gronbaek, Madhusudana Girija Sanal, Norbert Stefan, Ayako Suzuki, Giovanni Targher, Herbert Tilg, Ming-Lung Yu, Ming-Hua Zheng, Jacob George
Journal: Journal of Hepatology (2024)

Global survey of stigma among physicians and patients with nonalcoholic fatty liver diseaseJournal of HepatologyVol. 80Issue 3PreviewPatients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. Full-Text PDF A multisociety Delphi consensus statement on new fatty liver disease nomenclatureJournal of HepatologyVol. 79Issue 6PreviewThe 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. Full-Text PDF Open AccessDemocracy in ScienceJournal of HepatologyPreviewIt is not standard practice for the Editor-in-Chief to reply to a Letter to the Editor with a dedicated Editorial, but such a response is warranted in the case of the letter from Lonardo A. et al.,1 given its nature and the relevance of its content, which call into question the editorial strategy of the Journal of Hepatology regarding the new nomenclature of "metabolic fatty liver syndromes" endorsed by ALEH, AASLD and EASL after a long and difficult consensus process.2 Full-Text PDF Since many of us participated in the multi-society Delphi consensus statement on fatty liver disease nomenclature,[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multi-society Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. 2023; (S0168-8278(23)00418-X)Google Scholar we were interested in a recent article by Younossi and colleagues investigating potential stigma among patients with non-alcoholic fatty liver disease (NAFLD) and among healthcare providers.[2]Younossi Z.M. AlQahtani S.A. Alswat K. et al.Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol. 2023; (S0168-8278(23)05279-0)Abstract Full Text Full Text PDF Scopus (3) Google Scholar The authors concluded that the perception of NAFLD stigma varied among patients, providers, geographic locations, and sub-specialties.[2]Younossi Z.M. AlQahtani S.A. Alswat K. et al.Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol. 2023; (S0168-8278(23)05279-0)Abstract Full Text Full Text PDF Scopus (3) Google Scholar Of particular interest, only 8% of patients and 38% of doctors perceived stigma with use of the term.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multi-society Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. 2023; (S0168-8278(23)00418-X)Google Scholar European patients more commonly (57%) reported being comfortable with either term, with many selecting "fatty liver disease". Of note, while the Asia-Pacific region is home to ∼60% of the world's population, only 5% of the study population was from this region.[2]Younossi Z.M. AlQahtani S.A. Alswat K. et al.Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol. 2023; (S0168-8278(23)05279-0)Abstract Full Text Full Text PDF Scopus (3) Google Scholar Furthermore, only 48% of patients ever disclosed their disease to family members, a proportion which is not different from other diseases.[3]Awareness of family health history as a risk factor for disease --- United States. 2004Google Scholar The 2023 multi-society Delphi consensus statement suggested renaming NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD), where "fatty" was replaced by its synonym "steatotic".[2]Younossi Z.M. AlQahtani S.A. Alswat K. et al.Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol. 2023; (S0168-8278(23)05279-0)Abstract Full Text Full Text PDF Scopus (3) Google Scholar While there was consensus among panelists to change the definition by focusing on metabolic dysfunction and omitting the term "nonalcoholic", only 44% of respondents felt that the term" fatty" was stigmatizing in the first round. These results, and knowledge of how patients and their healthcare providers perceive stigma when referring to NAFLD, raises the question as to whether patients truly feel stigmatized by the term "fatty", particularly when it refers to an organ (the liver), rather than a person. On the contrary, patients might prefer using the term "fatty" when describing their liver as it facilitates communication with their healthcare providers on an equal footing. The term "steatotic", largely unfamiliar to most patients, could impede a much-needed conversation with their health providers, hindering an understanding of primary causes in many cases, such as overnutrition and/or insufficient physical activity. The notion that "fatty" may not be stigmatizing is also supported by liver patients' spokespeople, highlighting that "in some cultures being fat is regarded as a sign of good health".[4]Shiha G. Korenjak M. Casanovas T. et al.MAFLD 2022: an ELPA/ALPA/EASO-ECPO joint statement on disease stigma.J Hepatol. 2022; 77: 1717-1719Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Another study reported that this adjective is not invariably stigmatizing.[5]Méndez-Sánchez N. Pal S.C. Fassio E. et al.MAFLD: perceived stigma-a single-center Mexican patient survey.Hepatol Int. 2023; 17: 507-508Crossref PubMed Scopus (3) Google Scholar Another perspective is that patients are unlikely to know that "steatotic" is the adjective of steatosis. Importantly, "steatotic" cannot be found in any of the three online medical dictionaries nor in old books,[6]Lonardo A. MASLD co-aggregates with HCC in families-names change, fa(c)ts remain.Hepatoma Res. 2023; 9: 50https://doi.org/10.20517/2394-5079.2023.110Crossref Google Scholar implying that persons receiving a diagnosis of MASLD will probably find it difficult to intuitively grasp the essence of the condition and, therefore, largely depend on medical advice for explanations regarding their health status. Moreover, if these persons use 'Google' to search the meaning of "steatotic" or "steatosis", they will find that it indicates fat accumulation in the liver, a neutral fact that, however, does not fully encapsulate the core concept of the condition. Similarly, physicians frequently experience difficulties in explaining what "steatotic" means, other than using the adjective "fatty".[7]Clinicians Debate the Usefulness of NAFLD Name Change (medscape.com).Google Scholar Notably, the term "fatty" is perfectly acceptable and not considered offensive by many native English speakers. This likely explains why almost one-third of panelists in the Delphi consensus voted against this assertion. In addition, medical terms should communicate clearly to the patient and utilization of the adjective "steatotic" goes against efforts to promote better patient engagement and empowerment.[8]Hickmann E. Richter P. Schlieter H. All together now - patient engagement, patient empowerment, and associated terms in personal healthcare.BMC Health Serv Res. 2022; 22: 1116Crossref Scopus (24) Google Scholar Maintaining scientific integrity remains paramount in any ongoing debate surrounding this complex and heterogeneous condition. We assert that additional scientific data need to be accumulated to justify any specific context defined differently: NAFLD, metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD. The distinction among these nomenclatures, each defined differently, is crucial to further delineate the heterogeneous population and optimize classification for effective management strategies. A large cross-sectional study of individuals who had undergone liver ultrasound and vibration-controlled transient elastography as part of a routine check has shown that the MASLD definition captured more lean patients than the MAFLD definition.[9]Ramírez-Mejía M.M. Jiménez-Gutiérrez C. Eslam M. et al.Breaking new ground: MASLD vs. MAFLD-which holds the key for risk stratification?.Hepatol Int. 2023 Dec 21; (Epub ahead of print. PMID: 38127259)https://doi.org/10.1007/s12072-023-10620-yCrossref Scopus (1) Google Scholar Conversely, individuals with MAFLD exhibited a worse metabolic profile than those with MASLD alone. This study underscores that these nomenclatures and corresponding definitions capture different populations, with MAFLD identifying individuals with a worse metabolic profile while MASLD includes more lean individuals[9]Ramírez-Mejía M.M. Jiménez-Gutiérrez C. Eslam M. et al.Breaking new ground: MASLD vs. MAFLD-which holds the key for risk stratification?.Hepatol Int. 2023 Dec 21; (Epub ahead of print. PMID: 38127259)https://doi.org/10.1007/s12072-023-10620-yCrossref Scopus (1) Google Scholar Hence, the selection of the populations in future research should depend on specific research questions to be investigated. Enforcing the new MASLD nomenclature[10]Malhi H. Brown R.S. Jr. Lim J.K. et al.Precipitous changes in nomenclature and definitions-NAFLD becomes SLD: implications for and expectations of AASLD journals.Hepatology. 2023; 78: 1680-1681Crossref Scopus (0) Google Scholar without considering the context of studies could potentially generate confusion and hinder future research and new insights. Therefore, we propose that journals consider articles independently of the label used by researchers as long as the context is clearly defined. We would appreciate it if the Journal of Hepatology maintained a more flexible approach based on scientific rigor and knowledge-gain when judging future manuscripts. No financial support was received for preparing this manuscript. Stephen Caldwell - acknowledges the following Research Support: Gilead, GenFit, Ipsen, Zydus, Durect, Madrigal, Inventiva, Galectin, Cour, Exact, Ultragenyx, Target, Astra-Zeneca and Royalty Avanos. Robert G. Gish - has performed as Consultant and/or Advisor to (in the last two years): Abacus, Abbott, AbbVie, Albireo, Aligos, Altimunne, Antios, Arrowhead, AstraZeneca, Audentes Therapeutics, Corcept, Dynavax, Effectus, Eiger, Eisai, Enyo, Genentech, Genlantis, Gerson Lehrman Group, Gilead Sciences, GlaxoSmithKline, Helios, HepaTX, HepQuant, Intercept, Janssen, JBS Science, Kinnate Bio, Merck, Precision BioSciences, Pfizer, Seres Therapeutics, Topography Health, Tune Therapeutics, Venatorx, Virion. Current Activity with Scientific or Clinical Advisory Boards: AbbVie, Dynavax, Enyo, Genentech, Genlantis, Gilead, Helios, HepaTX, HepQuant, Intercept, Janssen, Merck, Pfizer, Prodigy. Current Clinical Trials Alliance: Topography Health. Chair Clinical Advisory Board: Prodigy. Advisory Consultant: Diagnostic Companies: Fibronostics, Fujifilm/Wako, Perspectum, Quest, Sonic Incytes. Data Safety Monitoring Board:Arrowhead, CymaBay Therapeutics, Durect, Kezar Life Sciences, Sagimet, Takeda. Consulting Confidentiality Agreements as of 2023: Abacus: 2023-current, Abbvie: 2017-current, Abbott: 2016-current, Access Biologicals: 2016-current, Active Genome Expressed Diagnostics: 2022-current, ADMA Biologics: 2017-current, AEC Partners: 2017-current, Aligos Therapeutics: 2020-current, Arena Pharmaceuticals Inc: 2018-current, Ark Biopharmaceutical Co Ltd: 2022-current, Arrowhead: 2011-current, Arterys Inc: 2018 – current, Alexion: 2018-current, Altimmune: 2020-current, Antios Therapeutics: 2018-current, AprosTx: 2020-current, AstraZeneca: 2023-current, Audentes Therapeutics: 2022-current, Bayer: 2019-current, Bausch/Salix: 2022-current, Chimigen: 2022-current, Cirina: 2017-current, Consumer Health Products Assoc: 2019-current, Corcept: 2023-current, CymaBay Therapeutics Inc: 2020-current, DiaSorin Inc: 2020-current, Dova Pharmaceuticals: 2017-current, DRG Abacus: 2018-current, DURECT Corporation: 2020-current, Dynavax: 2018-current, Echosens: 2020-current, Effectus: 2023-current, Eiger: 2015-current, Eisai: 2018-current, Enyo: 2017-current, Espresso Diagnostics: 2023-current, Exelixis: 2018-current, Fibronostics Inc: 2020-current, Forty-Seven Inc: 2019-current, Fujifilm Wako Diagnostics: 2019-current, Gilead: 2018-current, GlaxoSmithKline: 2022-current, HepQuant: 2018-current, HepaTx: 2017-current, HomShear Therapeutics: 2022-current, IDLogiq: 2020-current, Intellia: 2015-current, Intercept 2010 to current: approved to discuss what is in the public domain, Inotek: 2017-current, Consulting Confidentiality Agreements as of 2022 (continued), Iqvia: 2018-current, Janssen/J&J: 2015-current, JBS: 2022-current, KannaLife: 2019-current, Kezar Life Sciences Inc: 2021-current, Kinnate Bio: 2023-current, LabCorp: 2022-current, Laboratory for Advanced Medicine: 2019-current, Labyrinth Holdings: 2017-current, Life Line Screening: 2020-current, Lilly: 2017-current, Mallinckrodt: 2022-current, MedImmune: 2015-current, Merck: 2017-current, New Enterprise Associates: 2020-current, Ogilvy CommonHealth: 2017-current, Organovo: 2017-current, Orphalan: 2022-current, Patient Connect: 2017-current, Perspectum: 2021-current, Pfizer: 2021-current, Pharmaceutical Research Associates: 2021-current, Precision BioScience: 2023-current, ProdigY Biotech: 2020-current, Prometheus Laboratories: 2017-current, Refuah Solutions: 2020-current, Regulus Therapeutics: 2019-current, Sagimet Inc: 2021-current, Salix: 2019-current, Saol Bermuda Ltd: 2021-current, Seres Therapeutics: 2022-current, Shenzhen HEC Industrial Development: 2021-current, Shionogi Inc: 2017-current, Spring Bank: 2018-current, Syneos: 2022-current, Takeda: 2022-current, Tonghua Anrate Biopharmaceutical: 2021-current, Topography Health: 2020-current, Trimaran: 2017-current, Tune Therapeutics: 2022-current, VBI Vaccine: 2022-current, Venatorx: 2021-current, Viravaxx AG: 2021-current, Virion: 2023-current. These speaker bureau activities focus on HBV, HCV, HDV and liver cancer; specifically, epidemiology, diagnosis, and treatment. In addition, program presentations on vaccination for HBV and management of complications of cirrhosis. Dr. Gish has a speaker's contract to do promotional talks for: AbbVie, AstraZeneca, BMS, Diasorin, Eisai, Genentech, Gilead Sciences Inc., Intercept, Mallinckrodt, VBI Vaccines. Minor stock shareholder (liver space noted only): RiboSciences, CoCrystal. Stock Options: Abacus, Eiger, Genlantis, HepQuant, AngioCrine, HepaTx, JBS Science, Virion. Henning Gronbaek – declares he has received research funding from Intercept, Abbvie, NOVO Nordisk Foundation, Arla, and ADS AIPHIA Development Services AG; advisory board at NOVO Nordisk, Astrazeneca and Ipsen. Norbert Stefan – declares that he has received speaker honoraria from AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Genkyotex, Intercept Pharma, Lilly, Merck Sharp & Dohme, Novo Nordisk, Pfizer and Sanofi, has received research funding from AstraZeneca, DSM Nutritional Products, F. Hoffmann-La Roche and Sanofi, and has acted as an advisor for AstraZeneca, Genkyotex, GlaxoSmithKline Biologicals, Intercept Pharma, Lilly, Novo Nordisk, Pfizer and Sanofi. Ming-Lung Yu – Research support (grant) from Abbvie, BMS, Gilead, Merck and Roche diagnostics. Consultant of Abbvie, BMS, Gilead, Roche and Roche diagnostics. Speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. All other authors report no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details. All authors contributed equally to the conceptualization and writing (original draft preparation, review, and editing) of the manuscript. 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