Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index

Theja Channapragada¹, Sarah Batra², Breianna L Hummer^{2

3}, Vernon M Chinchilli⁴, Daniel Huang⁵, Rohit Loomba^{5

6

7}, Ian R Schreibman^{2

3

8}, Jonathan G Stine^{9

10

11

12

13}

Affiliations

¹ Department of Medicine, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
² Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
³ Fatty Liver Program, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
⁴ Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁶ Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
⁷ MASLD Research Center, University of California, Los Angeles, USA.
⁸ Cancer Institute, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. jstine@pennstatehealth.psu.edu.
¹⁰ Fatty Liver Program, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹¹ Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹² Liver Center, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹³ Cancer Institute, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.

PMID: 40900364
DOI: 10.1007/s10620-025-09361-9

Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index

Theja Channapragada et al. Dig Dis Sci. 2025.

. 2025 Sep 3.

doi: 10.1007/s10620-025-09361-9. Online ahead of print.

Authors

Theja Channapragada¹, Sarah Batra², Breianna L Hummer^{2

3}, Vernon M Chinchilli⁴, Daniel Huang⁵, Rohit Loomba^{5

6

7}, Ian R Schreibman^{2

3

8}, Jonathan G Stine^{9

10

11

12

13}

Affiliations

¹ Department of Medicine, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
² Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
³ Fatty Liver Program, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA.
⁴ Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁶ Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
⁷ MASLD Research Center, University of California, Los Angeles, USA.
⁸ Cancer Institute, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA. jstine@pennstatehealth.psu.edu.
¹⁰ Fatty Liver Program, Penn State Health-Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹¹ Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹² Liver Center, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.
¹³ Cancer Institute, Penn State Health- Milton S. Hershey Medical Center, Hershey, PA, USA. jstine@pennstatehealth.psu.edu.

PMID: 40900364
DOI: 10.1007/s10620-025-09361-9

Abstract

Purpose: Exercise training is recommended for all patients with metabolic dysfunction-associated steatotic liver disease. Whether exercise training improves liver histology independent of body weight loss remains controversial. Given the increasing reliance on non-invasive biomarkers as a surrogate for liver histology, we investigated the relationship between exercise training and improvement in liver histology using the MASH Resolution Index (MASH-RI), a validated composite score of multiple biomarkers, in a post hoc analysis of the NASHFit trial.

Methods: This study randomized adults with biopsy-proven MASH to moderate-intensity aerobic exercise training or standard of care for 20 weeks. Mediterranean-informed dietary counseling was provided to each group. Change in the MASH-RI was measured and compared between the two groups (n = 23).

Results: Applying the MASH-RI, those who performed exercise training achieved MASH resolution nearly three times more often (33% vs. 13%, p < 0.01) versus those who received standard of care. Exercise training improved individual biomarkers included in the MASH-RI, including ALT, AST, and MRI-PDFF.

Conclusion: Exercise training leads to MASH resolution, as defined by the MASH-RI at greater rates than standard lifestyle counseling. Future research is needed to determine how best to use the MASH-RI as a therapeutic monitoring tool to gauge response to lifestyle intervention.

Clinical trial registration: NCT03518294.

Keywords: Aerobic exercise; MASH Resolution Index; Metabolic dysfunction-associated steatohepatitis; Metabolic dysfunction-associated steatotic liver disease.

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Conflict of interest statement

Declarations. Conflict of interest: Dr. Stine receives or has received research support from Astra Zeneca, Galectin, Kowa, Novo Nordisk, Regeneron, and Zydus Therapeutics. Dr. Stine consults for Novo Nordisk and is on an advisory board for Madrigal. Following submission of this manuscript, Dr. Stine commenced employment with Astra Zeneca. Dr. Loomba serves as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse Bio, GNI, GRI Bio, Intercept, Ionis, Janssen Inc., Merck, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens. He is also co-founder of Liponexus, Inc. Ethical approval: All patients provided informed consent prior to being included in the study, and the study was approved by the Penn State Health Institutional Review Board (Study 8507). All research was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines, and Penn State Health local regulatory requirements. Permission to reproduce material from another source: No material from another source was reproduced.

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Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index

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Aerobic Exercise Training Leads to MASH Resolution as Defined by the MASH Resolution Index

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