Gastroenterology

Gastroenterology

Volume 158, Issue 7, May 2020, Pages 1999-2014.e1
Gastroenterology

MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease

https://doi.org/10.1053/j.gastro.2019.11.312Get rights and content

Fatty liver associated with metabolic dysfunction is common, affects a quarter of the population, and has no approved drug therapy. Although pharmacotherapies are in development, response rates appear modest. The heterogeneous pathogenesis of metabolic fatty liver diseases and inaccuracies in terminology and definitions necessitate a reappraisal of nomenclature to inform clinical trial design and drug development. A group of experts sought to integrate current understanding of patient heterogeneity captured under the acronym nonalcoholic fatty liver disease (NAFLD) and provide suggestions on terminology that more accurately reflects pathogenesis and can help in patient stratification for management. Experts reached consensus that NAFLD does not reflect current knowledge, and metabolic (dysfunction) associated fatty liver disease “MAFLD” was suggested as a more appropriate overarching term. This opens the door for efforts from the research community to update the nomenclature and subphenotype the disease to accelerate the translational path to new treatments.

Section snippets

Methods

Following discussions, an initial concept sheet was circulated to the panel of contributors. This revealed widespread agreement and consensus that it was time to revisit the nomenclature of metabolic fatty liver disease as a critical initial step for improved patient subphenotyping, clinical trials design, and ultimately, for personalization of medicine.

Subsequently, a manuscript was drafted, circulated to the panel, and feedback incorporated over several rounds of revision. To reach consensus

Impact on the Performance of Noninvasive Assessment of Fibrosis

Noninvasive fibrosis scores are commonly used to identify or exclude significant or advanced fibrosis in patients with fatty liver disease. However, a recent study suggested that the performance of scores such as the NAFLD fibrosis score and fibrosis 4 may vary across the life span, with lower specificity among older adults and lower accuracy in young adults.190 The performance of noninvasive scores and the used Transient Elastography liver stiffness cutoffs in different ethnic populations and

Is NAFLD the Right Name for Metabolic Liver Disease?

How do the preceding considerations influence our thinking on the need to revise the definition and nomenclature for NAFLD? It is clearly the time to do this. The suggestion of this consensus focuses on 4 aspects.

First, NAFLD was described as a condition of “exclusion,” which means that it exists only when other conditions, such as viral hepatitis B and C, autoimmune diseases, or alcohol intake above a particular threshold, are absent. However, with advancements in our understanding of the

Conclusion

The outdated NAFLD/NASH acronyms, the criteria for diagnosis, and a lack of adequate consideration of heterogeneity in risk profiles and treatment responsiveness represent barriers that hamper progress toward effective treatments. The consensus group has suggested an acronym (MAFLD) that we believe more accurately reflects current knowledge of fatty liver diseases associated with metabolic dysfunction that should replace NAFLD/NASH. In addition, we have identified gaps in current knowledge and

Acknowledgments

Members of the International Consensus Panel:

Arun Sanyal, Virginia Commonwealth University School of Medicine, Richmond, Virginia.

Brent Neuschwander-Tetri, Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, Missouri.

Claudio Tiribelli, Liver Center, Italian Liver Foundation, Trieste, Italy.

David E. Kleiner, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Elizabeth Brunt, Department of Pathology and Immunology

References (202)

  • S. Pelusi et al.

    Prevalence and risk factors of significant fibrosis in patients with nonalcoholic fatty liver without steatohepatitis

    Clin Gastroenterol Hepatol

    (2019)
  • M.A.T. Han et al.

    Rates of and factors associated with placebo response in trials of pharmacotherapies for nonalcoholic steatohepatitis: systematic review and meta-analysis

    Clin Gastroenterol Hepatol

    (2019)
  • S. McPherson et al.

    Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management

    J Hepatol

    (2015)
  • A. Mardinoglu et al.

    Broad Views of non-alcoholic fatty liver disease

    Cell Syst

    (2018)
  • J.P. Ong et al.

    Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease

    J Hepatol

    (2008)
  • J.L. Kuk et al.

    Age-related changes in total and regional fat distribution

    Ageing Res Rev

    (2009)
  • Y.H. Lee et al.

    Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008–2011)

    J Hepatol

    (2015)
  • J.M. Clark et al.

    Nonalcoholic fatty liver disease

    Gastroenterology

    (2002)
  • F. Norheim et al.

    Genetic and hormonal control of hepatic steatosis in female and male mice

    J Lipid Res

    (2017)
  • N.E. Rich et al.

    Racial and ethnic disparities in nonalcoholic fatty liver disease prevalence, severity, and outcomes in the United States: a systematic review and meta-analysis

    Clin Gastroenterol Hepatol

    (2018)
  • S.R. Mohanty et al.

    Influence of ethnicity on histological differences in non-alcoholic fatty liver disease

    J Hepatol

    (2009)
  • R. Guthold et al.

    Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1.9 million participants

    Lancet Glob Health

    (2018)
  • W. Dunn et al.

    Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)

    J Hepatol

    (2012)
  • L.B. VanWagner et al.

    Alcohol use and cardiovascular disease risk in patients with nonalcoholic fatty liver disease

    Gastroenterology

    (2017)
  • M. Boyle et al.

    The bidirectional impacts of alcohol consumption and the metabolic syndrome: cofactors for progressive fatty liver disease

    J Hepatol

    (2018)
  • V. Ajmera et al.

    Among patients with nonalcoholic fatty liver disease, modest alcohol use is associated with less improvement in histologic steatosis and steatohepatitis

    Clin Gastroenterol Hepatol

    (2018)
  • C. Lackner et al.

    Fibrosis and alcohol-related liver disease

    J Hepatol

    (2019)
  • M. Romero-Gomez et al.

    Treatment of NAFLD with diet, physical activity and exercise

    J Hepatol

    (2017)
  • F.M. Trovato et al.

    Mediterranean diet and non-alcoholic fatty liver disease. The need of extended and comprehensive interventions

    Clin Nutr

    (2015)
  • R. Loomba et al.

    Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease

    Cell Metab

    (2017)
  • T. Kawai et al.

    TLR signaling

    Semin Immunol

    (2007)
  • J. Ludwig et al.

    Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease

    Mayo Clin Proc

    (1980)
  • Z. Younossi et al.

    Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

    Nat Rev Gastroenterol Hepatol

    (2018)
  • S. Wiegand et al.

    Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16 390 overweight or obese children and adolescents

    Int J Obes (Lond)

    (2010)
  • P. Jepsen et al.

    Prognosis of patients with a diagnosis of fatty liver - A registry-based cohort study

    Hepatogastroenterology

    (2003)
  • H.T. Sorensen et al.

    Risk of cancer in patients hospitalized with fatty liver - A Danish cohort study

    J Clin Gastroenterol

    (2003)
  • Z. Younossi et al.

    Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

    Hepatology

    (2019)
  • Z.M. Younossi et al.

    The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe

    Hepatology

    (2016)
  • S.L. Friedman et al.

    Mechanisms of NAFLD development and therapeutic strategies

    Nat Med

    (2018)
  • R. Skoien et al.

    Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways

    Liver Int

    (2013)
  • J.F. Dufour

    Time to Abandon NASH?

    Hepatology

    (2016)
  • P. Loria et al.

    Should nonalcoholic fatty liver disease be renamed?

    Dig Dis

    (2005)
  • N.C. Dalkey

    Studies in the Quality of Life; Delphi and Decision-Making

    (1972)
  • H. Yki-Jarvinen et al.

    Heterogeneity of non-alcoholic fatty liver disease

    Liver Int

    (2015)
  • S. Singh et al.

    Fibrosis progression in nonalcoholic fatty liver versus nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies

    Gastroenterology

    (2014)
  • R. Loomba et al.

    Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis

    Hepatology

    (2012)
  • V. Nobili et al.

    NAFLD in children: new genes, new diagnostic modalities and new drugs

    Nat Rev Gastroenterol Hepatol

    (2019)
  • C.J. Pirola et al.

    Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

    World J Gastroenterol

    (2018)
  • J. Frith et al.

    Non-alcoholic fatty liver disease in older people

    Gerontology

    (2009)
  • J. Frith et al.

    Chronic liver disease in an ageing population

    Age Ageing

    (2009)
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    Conflicts of interest The authors disclose the following: Rajiv Jalan, on the international consensus panel, has research collaborations with Takeda and Yaqrit, and consults for Akaza and Yaqrit. Rajiv Jalan is the founder of Yaqrit Limited, which is developing UCL inventions for treatment of patients with cirrhosis. Rajiv Jalan is an inventor of ornithine phenylacetate, which was licensed by UCL to Mallinckrodt. He is also the inventor of Yaq-001, DIALIVE, and Yaq-005, the patents for which have been licensed by his university into a UCL spinout company, Yaqrit Ltd. The rest of authors declare no competing interests for this manuscript. The remaining authors disclose no conflicts.

    Funding Mohammed Eslam and Jacob George are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (APP1053206, APP1149976); and Project Grants (APP1107178 and APP1108422). Philip N. Newsome, on the international consensus panel, is funded and supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care or the NHS.

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