Changing epidemiology, global trends and implications for outcomes of NAFLD

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(3), P. 842 - 852

Published: May 10, 2023

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common globally, currently estimated to affect 38% of global population. A minority patients with NAFLD will progress cirrhosis or hepatocellular carcinoma, but total number this vast population that risk such severe outcomes is increasing. Worryingly, persons are affected by at an earlier age, suggesting they have longer time develop complications. With considerable changes in diet composition and urbanization, obesity type 2 diabetes among population, particular developing countries, proportion projected be further Yet, there large geographical discrepancies prevalence rates its inflammatory component non-alcoholic steatohepatitis (NASH). Such differences partly related differing socio-economic milieus, also genetic predisposition.This narrative review discusses recent epidemiology NASH from regional perspectives, as well special populations. We discuss consequences these can on hepatic extra-hepatic events.

Language: Английский

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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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Noninvasive Assessment of Liver Fibrosis in NAFLD

Clinical Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 21(8), P. 2026 - 2039

Published: April 14, 2023

Language: Английский

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WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification

Ultrasound in Medicine & Biology, Journal Year: 2024, Volume and Issue: 50(8), P. 1088 - 1098

Published: April 23, 2024

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance use available tools quantification liver fat content with These are attenuation coefficient, backscatter speed sound. All them raw data ultrasound beam to estimate content. This aim helping reader understanding how they work interpret results. Confounding factors discussed standardized protocol measurement acquisition suggested mitigate them. recommendations were based published studies experts' opinion but not formally graded because body evidence remained low at time drafting document.

Language: Английский

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Liver diseases: epidemiology, causes, trends and predictions

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

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Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD

Gut, Journal Year: 2023, Volume and Issue: 72(8), P. 1607 - 1619

Published: June 7, 2023

Non-alcoholic fatty liver disease (NAFLD) represents a major public health concern and is associated with substantial global burden of liver-related cardiovascular-related morbidity mortality. High total energy intake coupled unhealthy consumption ultra-processed foods saturated fats have long been regarded as dietary drivers NAFLD. However, there an accumulating body evidence demonstrating that the timing across day also important determinant individual risk for NAFLD metabolic conditions. This review summarises available observational epidemiological data describing associations between eating patterns disease, including negative effects irregular meal patterns, skipping breakfast night-time on health. We suggest these harmful behaviours deserve greater consideration in stratification management patients particularly 24-hour society continuous availability food up to 20% population now engaged shiftwork mistimed patterns. draw studies reporting liver-specific impact Ramadan, which unique real-world opportunity explore physiological fasting. By highlighting from preclinical pilot human studies, we present further biological rationale manipulating improve discuss how this may be mediated through restoration natural circadian rhythms. Lastly, comprehensively landscape trials intermittent fasting time-restricted offer look future about strategies benefit non-alcoholic steatohepatitis.

Language: Английский

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Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(6), P. 1374 - 1384

Published: Aug. 28, 2023

•Nationwide multigenerational study of 292,274 family members people with biopsy-confirmed MASLD and comparators.•MASLD first-degree relatives had increased hazards HCC, major adverse liver outcomes liver-related mortality.•The absolute risk HCC was low, only one extra case per 900 over 20 years follow-up.•Spouses individuals also a higher relative developing outcomes.•Liver disease progressed more rapidly in concomitant diseases. Background & AimsMetabolic dysfunction-associated steatotic (MASLD; formerly NAFLD) is the fastest growing cause hepatocellular carcinoma (HCC) worldwide. However, whether share an unknown.MethodsThis nationwide cohort involved all Swedish adults diagnosed biopsy-proven (1969−2017), matched general population comparators. Using Multi-generation Register, we identified 38,018 (FDRs: parents, siblings, offspring) 9,381 spouses patients MASLD, as well 197,303 comparator FDRs 47,572 spouses. We used Cox proportional models to calculate adjusted hazard ratios (aHRs) for (cirrhosis, decompensated or transplantation), mortality, extrahepatic cancer, non-liver-related mortality.ResultsOver median 17.6 years, rate primary outcome vs. (13 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36−2.37). The further fibrosis/cirrhosis (aHR 2.14, 1.07−4.27; PHeterogeneity = 0.03). rates (73 51/100,000 PY; 1.52, 1.36−1.69) mortality (20 11/100,000 1.67−2.74). any chronic condition experienced accelerated progression 1.47, 1.29-1.67). were at risks (86 74/100,000 1.23, 1.01−1.51) (25 19/100,000 1.93, 1.15−3.23), but not 1.43, 0.87−2.35).ConclusionsThere distinct familial clustering families progressive disease, are low.Impact implicationsMetabolic termed clusters high genetic susceptibility shared environmental factors, other largely unknown. This large involving (first-degree spouses) comparators found slightly relatives, cirrhosis MASLD. findings this provide large-scale evidence inform clinical practice guidelines recommendations on early identification morbidity mortality. Metabolic Over 0.87−2.35). There low.

Language: Английский

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Unmasking the enigma of lipid metabolism in metabolic dysfunction-associated steatotic liver disease: from mechanism to the clinic

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 27, 2023

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly defined as non-alcoholic fatty (NAFLD), is a disorder marked by the excessive deposition of lipids in liver, giving rise to spectrum pathologies encompassing steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. Despite alarming increase its prevalence, US Food Drug Administration has yet approve effective pharmacological therapeutics for clinical use. MASLD characterized accretion within hepatic system, arising from disarray lipid provision (whether through absorption circulating or de novo lipogenesis) elimination (via free acid oxidation secretion triglyceride-rich lipoproteins). This leads accumulation lipotoxic substances, cellular pressure, damage, fibrosis. Indeed, regulation metabolism pathway intricate multifaceted, involving myriad factors, such membrane transport proteins, metabolic enzymes, transcription factors. Here, we will review existing literature on key process understand latest progress this molecular mechanism. Notably, lipogenesis roles two main factors other enzymes are highlighted. Furthermore, delve into realm drug research, examining recent made understanding MASLD. Additionally, outline prospective avenues future research based our unique perspectives.

Language: Английский

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Genetics of MASLD: The State of Art Update.

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 22(11), P. 2177 - 2187.e3

Published: July 31, 2024

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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