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Publications

Journal Article Epublish

PubMed: 42928097 DOI: 10.1186/s12876-026-05137-1

Cardiorespiratory fitness is inversely associated with non-invasive markers of hepatic steatosis and fibrosis: a cross-sectional study of 39,197 UK adults.

BMC Gastroenterol 26(1)

Authors: Scott A Willis, Kevin Deighton, Christopher Goodwin, Daniel J Cuthbertson, Jonathan G Stine, Shelley E Keating, Christopher J A Pugh, Gaël Ennequin, David J Stensel, Guruprasad P Aithal, James A King

Affiliations

  • National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK.
  • NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.
  • Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK.
  • Nuffield Health Research Group, Nuffield Health, Epsom, UK.
  • Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
  • Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
  • Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
  • School of Human Movement and Nutrition Sciences, The University of Queensland, St Lucia, QLD, Australia.
  • Centre for Cardiovascular Research, Innovation and Development, Cardiff Metropolitan University, Cardiff, UK.
  • Centre for Health, Activity and Wellbeing Research, Cardiff Metropolitan University, Cardiff, UK.
  • Laboratory of the Metabolic Adaptations to Exercise Under Physiological and Pathological Conditions (AME2P), Clermont Auvergne University, Clermont-Ferrand, France.
  • International Research Chair Health in Motion, Clermont Auvergne University Foundation, Clermont-Ferrand, France.
  • National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK. NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.
  • Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK. NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK.
  • NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.

Abstract

BACKGROUND

Cardiorespiratory fitness (CRF) is a powerful predictor of numerous health outcomes; however, its relationship with liver health remains unclear. This study examined the associations of CRF with non-invasive markers of liver steatosis and fibrosis in a large, health-screening cohort, and explored potential effect modification by demographic, cardiometabolic, and clinical factors.

METHODS

In this independent healthcare-based cross-sectional study of 39,197 UK adults (32% female; mean ± SD, age 45.8 ± 9.0 years), CRF was objectively estimated as peak oxygen uptake (ml∙kg -1∙min -1) during submaximal treadmill and cycle ergometer tests. Hepatic steatosis and fibrosis were defined using validated non-invasive indices: Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) for steatosis, and Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Score (NFS) for fibrosis. Multinomial logistic regression examined associations between CRF and low-, intermediate-, and high-risk categories for each index, adjusting for demographic, cardiometabolic, and clinical covariates (excluding component variables of the respective indices).

RESULTS

For FLI and HSI, each 1 ml∙kg -1∙min -1 higher CRF was associated with 3-5% lower odds of intermediate steatosis risk and 8-9% lower odds of high steatosis risk (P < 0.001). For FIB-4 and NFS, higher CRF was associated with 1-3% lower odds of intermediate fibrosis risk and 2-6% lower odds of high fibrosis risk (P ≤ 0.011). Associations were stronger in females and weaker in individuals with less favourable metabolic profiles.

CONCLUSIONS

Higher CRF was associated with lower odds of hepatic steatosis and fibrosis across multiple validated non-invasive indices. These findings highlight CRF as an integrative biomarker of hepatic and cardiometabolic health, and modifiable target for steatotic liver disease prevention and management.

MeSH

Cross-Sectional Studies, Fibrosis, Cardiorespiratory Fitness, Liver, Gastrointestinal Diseases, Demography