Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease

Abstract

Background and aims: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training.

Methods: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness.

Results: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m². Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O₂peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight).

Conclusion: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Keywords: NAFLD; NASH; fatty liver; lifestyle intervention; physical activity.

Figure 1.

Change in absolute liver fat (a), proportion achieving ≥30% liver fat reduction (b) and proportion achieving both ≥30% liver fat reduction and >17 IU/L ALT reduction (c) in exercise vs. control. Data are within-group estimated marginal mean change from baseline (95%CI) from linear mixed model or within-group proportion (%)

Figure 2.

Change in absolute V̇O₂peak (a), proportion achieving ≥10% gain in V̇O₂peak (b), change in ventilatory threshold (c) and change in exercise capacity (d) in exercise vs. control. Data are within-group estimated marginal mean change from baseline (95%CI) from linear mixed model or within-group proportion (%).