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

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.