MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up

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Abstract

Background and Aims:

A new term, metabolic dysfunction–associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the “MASLD/MetALD” and “no steatotic liver disease (SLD)” groups in individuals with any CMRF.

Approach and Results:

A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the “MASLD,” “MetALD,” and “no SLD” groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the “MASLD” group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95–1.14], p = 0.413), cardiovascular (0.88 [0.75–1.04], p = 0.139), or cancer (1.06[0.84–1.33], p = 0.635) mortality risk compared to the “no SLD” group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05–1.89], p = 0.022), cancer (2.35 [1.33–4.16], p = 0.004), and liver (15.04 [2.96–76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4).

Conclusions:

In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

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Most cited references 24

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

Zobair Younossi, Quentin M Anstee, Milena Marietti … (2018)

NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.

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MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease

Mohammed Eslam, Arun Sanyal, Jacob George (2020)

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.

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A multi-society Delphi consensus statement on new fatty liver disease nomenclature

Mary Rinella, Jeffrey V Lazarus, Vlad Ratziu … (2023)

The 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. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.

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Author and article information

Contributors

Minsun Kwak: (View ORCID Profile)

Zhenghui Gordon Jiang: (View ORCID Profile)

Yee Hui Yeo: (View ORCID Profile)

Journal

Title: Hepatology

Publisher: Ovid Technologies (Wolters Kluwer Health)

ISSN (Print): 0270-9139

Publication date (Electronic): May 13 2024

Affiliations

[1 ]Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea

[2 ]Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA

[3 ]Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

[4 ]Houston Methodist Hospital, Houston, Texas, USA

[5 ]Department of Houston Research Institute, Houston, Texas, USA

Article

DOI: 10.1097/HEP.0000000000000925

PubMed ID: 38739848

SO-VID: 81885b47-b250-4cc0-ae48-cc90a6a66f00

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