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

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.