Exercise training improves serum biomarkers of liver fibroinflammation in patients with metabolic dysfunction‐associated steatohepatitis
Open accessAbstract
Background and Aims: Exercise training is recommended for all patients with metabolic dysfunction‐associated steatotic liver disease and may reverse liver fibrosis. Whether exercise training improves liver fibrosis without body weight loss remains controversial. We further investigated this relationship using serum biomarkers of liver fibroinflammation in a post hoc analysis of an exercise trial where patients did not lose significant body weight. Methods: In the NASHFit trial, patients with metabolic dysfunction‐associated steatohepatitis were randomized to receive either moderate‐intensity aerobic exercise training or standard clinical care for 20 weeks. Mediterranean‐informed dietary counselling was provided to each group. Change in serum biomarkers was measured and compared between the two groups. Results: Exercise training led to improvement in serum biomarkers of liver fibroinflammation, including (1) ≥17 IU/L reduction in alanine aminotransferase (ALT) in 53% of individuals in the exercise training group compared to 13% in the standard clinical care group ( p < 0.001; mean reduction 24% vs. 10% respectively) and (2) improvement in CK18 (−61 vs. +71 ng/mL, p = 0.040). ALT improvement ≥17 IU/L was correlated with ≥30% relative reduction in magnetic resonance imaging‐measured liver fat and PNPLA3 genotype. Conclusion: Exercise training improves multiple serum biomarkers of liver fibroinflammation at clinically significant thresholds of response without body weight loss. This study provides further evidence that exercise training should be viewed as a weight‐neutral intervention for which response to intervention can be readily monitored with widely available non‐invasive biomarkers that can be applied at the population level.
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Adults with biopsy-proven MASH who performed aerobic exercise training for 20 weeks were four times more likely to achieve clinically meaningful improvement in ALT (reduction ≥ 17 IU/L) and three times more likely to achieve clinically meaningful improvement in MRI-PDFF (≥ 30% relative reduction).
“the study found that adults with biopsy-proven MASH who performed aerobic exercise training for 20 weeks were four times more likely to achieve clinically meaningful improvement in ALT (reduction ≥ 17 IU/L) and three times more likely to achieve clinically meaningful improvement in MRI-PDFF (≥ 30% relative reduction) [9, 22].”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [9]
Exercise intervention did not lead to any clinically significant changes in body weight, with an average weight loss of < 3%.
“Importantly, exercise intervention did not lead to any clinically significant changes in body weight, with an average weight loss of < 3% [9].”
From Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index (2026) · cites this paper as [9]
Six RCTs on aerobic exercise showed a significant reduction in liver fat compared to controls.
“Six RCTs on aerobic exercise showed a significant reduction in liver fat compared to controls [67, 69, 71, 75, 76, 79]”
No differences were found in waist circumference for aerobic exercise interventions compared to control.
“Nine aerobic interventions reported WC [69–72, 74, 75, 78, 79, 90], but no differences were found in comparison to control”
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- Authors
- Harris, S. J., Smith, N., Hummer, B., Schreibman, I. R., Faust, A. J., Geyer, N. R., Chinchilli, V. M., Sciamanna, C., Loomba, R., & Stine, J. G.
- Affiliations
- Pennsylvania State University (US)
- College of Medicine, The Pennsylvania State University Hershey Pennsylvania USA
- University of California San Diego (US)
- Corresponding author
- Stine, Jonathan G.
- ORCID
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2023-11-28
- Volume
- 44
- Issue
- 2
- Pages
- 532-540
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- PMC
- PMC10844956
- OpenAlex
- W4389085108
- Cited by
- 31
- References
- 47
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 10 · 2023: 1
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (K23DK131290, L30DK118601)
- National Center for Advancing Translational Sciences (5UL1TR001442, UL1TR002014, UL1TR000127)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK120515, R01DK124318, R01DK121378, R01DK106419, U01DK130190, U01DK061734)
- National Heart, Lung, and Blood Institute (P01HL147835)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- exercise training, nonalcoholic steatohepatitis, liver fibrosis, serum biomarkers, alanine aminotransferase, cytokeratin 18, liver fat, aerobic exercise, Mediterranean diet
- MeSH terms
- Humans, Liver, Liver Cirrhosis, Biomarkers, Weight Loss, Exercise, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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