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Cited by 98Liver Disease Diagnosis and TreatmentNutrition and Health in AgingBody Composition Measurement Techniques

Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD

Open access
Linge, Jennifer, Ekstedt, Mattias, Dahlqvist Leinhard, Olof·2021·JHEP Reports
DOI 10.1016/j.jhepr.2020.100197PMC PMC7868647
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Abstract

Background & Aims Sarcopenia and frailty are recognised as important factors in later stages of liver disease. However, their role in non-alcoholic fatty liver disease (NAFLD) is not yet fully understood. In this study we investigate the associations of MRI-measured adverse muscle composition (AMC: low muscle volume and high muscle fat) with poor function, sarcopenia, and metabolic comorbidity within NAFLD in the large UK Biobank imaging study. Methods A total of 9,545 participants were included. Liver fat, fat-tissue free muscle volume, and muscle fat infiltration were quantified using a rapid MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalised muscle volume z-score (sex- and body size-specific) was calculated and combined with muscle fat infiltration for AMC detection. The following outcomes were investigated: functional performance (hand grip strength, walking pace, stair climbing, falls) and metabolic comorbidities (coronary heart disease, type 2 diabetes). Sarcopenia was detected by combining MRI thresholds for low muscle quantity and low hand grip strength according to the European working group definition. Results The prevalence of sarcopenia in NAFLD (1.6%) was significantly lower ( p <0.05) compared with controls without fatty liver (3.4%), whereas the prevalence of poor function and metabolic comorbidity was similar or higher. Of the 1,204 participants with NAFLD, 169 (14%) had AMC and showed 1.7–2.4× higher prevalence of poor function (all p <0.05) as well as 2.1× and 3.3× higher prevalence of type 2 diabetes and coronary heart disease ( p <0.001), respectively, compared with those without AMC. Conclusions AMC is a prevalent and highly vulnerable NAFLD phenotype displaying poor function and high prevalence of metabolic comorbidity. Sarcopenia guidelines can be strengthened by including cut-offs for muscle fat, enabling AMC detection. Lay summary Today, it is hard to predict whether a patient with fatty liver disease will progress to more severe liver disease. This study shows that measuring muscle health (the patient's muscle volume and how much fat they have in their muscles) could help identify the more vulnerable patients and enable early prevention of severe liver disease.

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  • Muscle mass and myosteatosis independently predict muscle strength, physical performance, morbidity, and mortality.

    “In turn, muscle mass and myosteatosis independently predict muscle strength, physical performance, morbidity, and mortality.4–7”

    From Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial (2025) · cites this paper as [6]

    The Results (‘Muscle composition within NAFLD’; page not provided) link combined low muscle volume and high muscle fat to poor functional performance and greater prevalence of coronary heart disease and type 2 diabetes. They report few significant functional differences for either abnormality alone, so the paper does not establish that both independently predict all these outcomes. Mortality was not assessed, and the Discussion describes the study as primarily cross-sectional. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Accumulating evidence suggests that using the muscle volume z-score improves the association with muscle function and mobility, and is associated with morbidity and mortality.

    “Accumulating evidence suggests that using the muscle volume z-score improves the association with muscle function and mobility, and is associated with morbidity and mortality.[58][59][60][61]”

    From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [59]

    The Introduction (page not provided) says a personalised muscle volume z-score was associated with poor function and increased hospitalisation, whereas muscle volume alone inadequately detected those outcomes. The Methods include walking pace and stair climbing as mobility-related outcomes. Our copy does not report an association with mortality, so that part of the claim is unsupported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The prevalence of adverse muscle composition appears higher in cardiometabolic disease states such as metabolic-associated steatotic liver disease and is similarly associated with excess morbidity with two- to threefold higher prevalence of diabetes and coronary heart disease.

    “The prevalence of adverse muscle composition appears higher in cardiometabolic disease states such as metabolicassociated steatotic liver disease and is similarly associated with excess morbidity with two-to threefold higher prevalence of diabetes and coronary heart disease.59”

    From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [59]

  • A combined assessment of muscle quantity and muscle fat provides a more complete description of muscle health that has been shown to improve performance in identifying high-risk individuals.

    “Therefore, a combined assessment provides a more complete description of muscle health that has been shown to improve the performance in identifying high-risk individuals. [58][59]59][60][61]65,67,69”

    From Changes in lean body mass with <scp>glucagon‐like peptide</scp> ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [59]

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Authors
Linge, J., Ekstedt, M., & Dahlqvist Leinhard, O.
Affiliations
Linköping University (SE)
Corresponding author
Linge, Jennifer
ORCID
Venue
JHEP Reports
Publisher
Elsevier BV
Published
2021-02
Volume
3
Issue
1
Pages
100197
ISSN
2589-5559 (ISSN-L)
DOI
10.1016/j.jhepr.2020.100197
PMC
PMC7868647
OpenAlex
W3096023256
Cited by
98
References
34
Citations by year
2026: 15 · 2025: 19 · 2024: 26 · 2023: 11 · 2022: 15 · 2021: 11 · 2020: 1
FWCI
6.81
Type
journal article
Language
en
Open access
Licence
Locations
  • JHEP Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Physiology › Body Composition Measurement Techniques
Keywords
non-alcoholic fatty liver disease, sarcopenia, muscle fat infiltration, muscle volume, functional performance, grip strength, falls, type 2 diabetes, coronary artery disease, metabolic comorbidities, liver disease progression

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