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

Journal of Lipid Research, Journal Year: 2023, Volume and Issue: 65(1), P. 100485 - 100485

Published: Dec. 14, 2023

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

Language: Английский

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Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5640 - 5640

Published: May 22, 2024

The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk cardio-metabolic cancer. In recent years, terminological evolution from “nonalcoholic fatty disease” (NAFLD) to “metabolic dysfunction-associated (MAFLD) and, finally, steatotic (MASLD) has been paralleled by increased knowledge mechanisms linking local hepatic) systemic pathogenic pathways. As a consequence, need for an appropriate classification individual phenotypes oriented investigation innovative therapeutic tools. Besides well-known role lifestyle change, number pharmacological approaches have explored, ranging antidiabetic drugs agonists acting on gut–liver axis at level (mainly farnesoid X receptor (FXR) agonists, PPAR thyroid hormone agonists), anti-fibrotic anti-inflammatory agents. intrinsically complex pathophysiological history MASLD makes selection single effective treatment major challenge, so far. this evolving scenario, cooperation between different stakeholders (including subjects risk, health professionals, pharmaceutical industries) could significantly improve management disease implementation primary secondary prevention measures. high healthcare search new, effective, safe pressing need, together accurate characterization phenotypes. Recent promising advances indicate that we may soon enter era precise personalized therapy MASLD/MASH.

Language: Английский

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Associations between estimated glucose disposal rate and arterial stiffness and mortality among US adults with non-alcoholic fatty liver disease

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 8, 2024

Background The estimated glucose disposal rate (eGDR), an effective indicator of insulin resistance, has been related to acute coronary syndrome, ischemic stroke and heart failure. This study aims explore the relationship between eGDR arterial stiffness, all-cause mortality cardiovascular in patients with non-alcoholic fatty liver disease (NAFLD). Methods Participants NAFLD were chosen from National Health Nutrition Examination Survey (NHANES) 1999 2018. main outcomes are stiffness (represented by pulse wave velocity, ePWV), mortality. Multiple cox regression models, restricted cubic spline, sensitivity analysis subgroup carried out investigate correlation resistance indicators stiffness. Furthermore, receiver operating characteristic curves used compare predictive value triglyceride-glucose (TyG) index homeostasis model assessment (HOMA-IR) for Results In this study, a total 4,861 participants included analysis. After adjusting confounding factors multivariate weighted model, was inversely associated (Q4 vs. Q1, HR =0.65 (0.48-0.89, P=0.01) =0.35 (0.19-0.65, P&lt;0.001). Compared TyG HOMA-IR, shows excellent (0.588 0.550 0.513, P &lt; 0.001) (0.625 0.553 0.537, 0.001). addition, we found significant negative (β=-0.13(-0.14–0.11, P&lt; However, HOMA-IR showed no Conclusions Low (an resistance) levels increased risk United States.

Language: Английский

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Prevalence of steatotic liver disease, advanced fibrosis and cirrhosis among community-dwelling overweight and obese individuals in the USA

Gut, Journal Year: 2024, Volume and Issue: 73(12), P. 2045 - 2053

Published: Aug. 7, 2024

There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, cirrhosis using MRI-based methods in USA. The aim this study was to fill that gap knowledge by prospectively determining steatotic liver disease (SLD) its subcategories, fibrosis residing

Language: Английский

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Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 124, P. 35 - 39

Published: April 22, 2024

The medical term nonalcoholic fatty liver disease (NAFLD) was coined in 1986 for a condition that has since become the most prevalent disorder worldwide. In last 3 years, global professional community launched 2 consecutive efforts to purge NAFLD from dictionary and recommended new terms based on pathophysiology rather than distinction similar conditions featuring steatosis. A consensus by renowned clinical scholars primarily residing Asian-Pacific region introduced metabolic dysfunction-associated (MAFLD) as name replace 2020. 2023, nomenclature classification resulting steatotic (MASLD) developed large expert panel under auspices of leading societies Europe Americas. These marked rapid shifts have garnered attention many researchers clinicians across globe due multilevel impact frequent potentially progressive chronic both adult pediatric populations. proposed terminologies differ several ways but they more common differences. They capture key features associated with cardiometabolic risk factors significant all-cause liver-related mortality. framework MASLD incorporated innovative aspects MAFLD while conceptual disparities remain work progress, should focus insights into pathogenesis, outcome trajectories, prevention, treatment. Here, some these challenges are discussed facilitate this process.

Language: Английский

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Associations between systemic inflammatory biomarkers and metabolic dysfunction associated steatotic liver disease: a cross-sectional study of NHANES 2017–2020

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 29, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a primary cause of chronic disease, with potential progression to cirrhosis and hepatocellular carcinoma (HCC). Although systemic inflammatory biomarkers are associated diseases, their specific role in MASLD remains unclear. This study examines the association between MASLD. cross-sectional enrolled 6613 adults aged 20 years or older from National Health Nutrition Examination Survey (NHANES) spanning 2017 March 2020. Among these participants,, 34.67% were 40-59 years, 50.85% female, 63.26% Non-Hispanic White. We investigated 10 biomarkers: ALI, SIRI, SII, SIPS, IBI, NLR, PLR, CAR, LMR, PNI. Logistic regression models performed assess linear Restricted cubic spline (RCS) was employed explore nonlinear relationships risk. Additionally, subgroup analyses conducted examine influence various demographic clinical characteristics on observed associations. After adjusting for key confounders, NLR PLR exhibited negative risk, while PNI opposite (P < 0.05). Most biomarkers, including PNI, significant non-linear correlations Subgroup revealed substantial age-related differences ALI as well varying risk across cardiovascular outcomes Systemic significantly Large-scale prospective studies warranted confirm findings elucidate underlying mechanisms.

Language: Английский

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Role of Alcohol in Steatotic Liver Disease: Impact on Patients with Cardiometabolic Risk Factors

Digestive Diseases and Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The new definition of steatotic liver disease (SLD), as a broader concept, was step forward in the increasing recognition substantial overlap between alcohol and cardiometabolic risk factors (CMRFs), continuum way. spectrum pathophysiological aspects, ranging from steatosis to fibrosis, has similarities MASLD ALD. Also, there is now considerable evidence that association metabolic dysfunction with increased consumption impacts on severe prognosis. MetALD class, recently proposed, shows clear differences prognosis when comparing ALD groups. However, room for improvement, such considering role previous intake, fluctuations over time, including binge drinking, refinement assessment, better understanding biomarkers. In summary, SLD no doubt significant but classification needs be dynamic adapting patients needing frequent reassessment. Furthermore, it brings opportunities research interaction CMRFs.

Language: Английский

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Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases

Circulation Research, Journal Year: 2024, Volume and Issue: 135(1), P. 222 - 260

Published: June 20, 2024

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks intimately participate in the progression severity of cardiometabolic diseases. In this review, we systemically summarized updated biological functions pathways diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, diabetes. We further discussed cellular molecular mechanisms pathway–mediated regulation diseases highlighted emerging clinical advances improve these pathological conditions by targeting metabolites factors.

Language: Английский

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Usefulness of health checkup‐based indices in identifying metabolic dysfunction‐associated steatotic liver disease

JGH Open, Journal Year: 2024, Volume and Issue: 8(6)

Published: June 1, 2024

The application of indices in the context metabolic dysfunction-associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate ability alanine aminotransferase (ALT), fatty index (FLI), and hepatic steatosis (HSI) identify MASLD during health checkups.

Language: Английский

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Associations between multiple metabolic biomarkers with steatotic liver disease subcategories: A 5-year Chinese cohort study

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: 6(1), P. 101884 - 101884

Published: Jan. 1, 2025

Highlights•RBP-4, FGF-21, adiponectin, and osteocalcin enhance risk prediction for SLD•Adiponectin shows the best predictive performance SLD•Elevated FGF-21 RBP-4 emphasize metabolic alcohol management, respectivelySummaryThe effectiveness of established biomarkers non-alcoholic fatty liver disease (NAFLD) within updated framework steatotic (SLD) remains uncertain. This cohort study examines association four biomarkers—retinol-binding protein 4 (RBP-4), fibroblast growth factor 21 (FGF-21), osteocalcin—with SLD its subtypes: dysfunction-associated (MASLD) dysfunction with alcohol-related (MetALD)/alcohol-related (ALD). Among 3,504 Chinese participants aged 55–70, 938 (26.8%) have developed over 5 years, including 871 MASLD 67 MetALD/ALD. The findings indicate that models incorporating RBP-4, improve accuracy beyond conventional models. Notably, adiponectin emerges as most versatile marker, while elevated baseline levels or specific needs interventions, respectively, supporting tailored precision medicine strategies.Graphical abstract

Language: Английский

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