Exercise training improves serum biomarkers of liver fibroinflammation in patients with metabolic dysfunction-associated steatohepatitis.

Sara J Harris, Nataliya Smith, Breianna Hummer, Ian R Schreibman, Alison J Faust, Nathaniel R Geyer, Vernon M Chinchilli, Chris Sciamanna, Rohit Loomba, Jonathan G Stine

Journal: Liver international : official journal of the International Association for the Study of the Liver 2024;44(2):532-540

PMID: 38014619

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Plain Language Summary

Metabolic dysfunction-associated steatohepatitis (MASH) is a more severe form of fatty liver disease that includes liver inflammation and damage. Without effective treatment, MASH can progress to liver fibrosis, cirrhosis, and liver failure. While medications are still in development, lifestyle changes such as exercise are central to its management. This study aimed to evaluate whether structured exercise training can improve blood biomarkers of liver fibroinflammation in patients with MASH. This research was a post-hoc analysis of the previously published 20-week NASHFit trial. The study included sedentary adults with biopsy-confirmed MASH, who were randomised to receive either an exercise training intervention (n=15) or standard clinical care (n=8). Results showed that exercise significantly reduced serum markers of liver inflammation and fibrosis compared to those given standard of care and independent of weight loss. Additionally, improvements were also noted in body composition (fat mass reduction) and blood sugar control compared to those given standard of care. The authors concluded that regular exercise training improves liver health in patients with MASH, reflected by significant improvements in non-invasive blood-based markers of liver fibroinflammation. These findings are clinically relevant for healthcare practitioners because they provide further evidence that exercise is a powerful, non-pharmacological treatment strategy for MASH and supports using serum biomarkers to monitor response to lifestyle interventions.

Abstract

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.

Address: College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA.; Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.; Fatty Liver Program, Penn State Health-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.; Liver Center, Penn State Health-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.; Department of Public Health Sciences, The Pennsylvania State University-College of Medicine, Hershey, Pennsylvania, USA.; Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA.; NAFLD Research Center, University of California San Diego, San Diego, California, USA.; Cancer Institute, Penn State Health-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

DOI: 10.1111/liv.15769