PubMed1 Apr 2026Obesity reviews : an official journal of the International Association for the Study of Obesity● 3/10i Comparative Efficacy of Different Exercise Interventions on Intrahepatic Lipid Content, Glucose Homeostasis, and Liver Function in Adults With and Without Nonalcoholic Fatty Liver Disease: A Systematic Review With Pairwise and Network Meta-Analyses.
Khalafi M, Fatolahi S, Symonds ME, Rosenkranz SK, Dinizadeh F et al.
High-intensity interval training reduced intrahepatic lipid content most effectively (p-score 0.95), followed by aerobic training (0.77), combined training (0.52), and resistance training (0.10) in adults with and without NAFLD. Network meta-analysis of 38 studies with 1,880 participants comparing exercise interventions. This provides the first head-to-head comparison ranking different exercise modalities for liver fat reduction, filling a critical evidence gap for clinical guidelines and treatment algorithms. Exercise also reduced fasting glucose, insulin, HbA1c, and liver enzymes ALT/AST compared to no exercise.
Strategic Signal
This systematic review reinforces exercise as first-line NAFLD treatment, potentially strengthening payer resistance to expensive NAFLD therapies like Madrigal's resmetirom in US and EU markets. Health technology assessment bodies will likely reference this data to justify stepped care approaches requiring lifestyle modification failures before drug coverage. The evidence supports current clinical guidelines positioning exercise before pharmaceutical intervention, creating higher reimbursement barriers for emerging NAFLD treatments.
Liver/NASH
Original Abstract
OBJECTIVES: This study investigated the effects of different exercise interventions on intrahepatic lipid content and markers of glucose homeostasis and liver function in adults with and without nonalcoholic fatty liver disease (NAFLD). METHODS: A comprehensive search was conducted in PubMed, Scopus, Web of Science, and EMBASE using three primary keywords including "exercise training," "liver fat," and "randomization" from inception to August 2025. Eligible studies were those that compared exercise training with either nonexercise groups or other types of exercise training. RESULTS: Thirty-eight studies comprising 1880 participants were included. Exercise training was more effective for reducing intrahepatic lipids [SMD: -0.33, p = 0.001], confirmed through subgroup analyses based on age, health status, body mass index, intervention duration, specific health status, frequency of weekly exercise sessions, biological sex, steatosis classification, and weight change%. Based on the p-score rankings, the intervention that was likely to be the most effective for lowering intrahepatic lipids was high-intensity interval training (p = 0.95), followed by aerobic training (p = 0.77), combined aerobic and resistance training (p = 0.52), and resistance training (p = 0.10). Secondarily, exercise training reduced fasting blood glucose [WMD: -2.27 mg/dL, p = 0.007], fasting insulin [SMD: -0.16, p = 0.02], glycated hemoglobin [SMD: -0.13, p = 0.03], and liver function enzymes including alanine aminotransferase (ALT) [WMD: -3.72 U/L, p = 0.001] and aspartate aminotransferase (AST) [WMD: -3.51 U/L, p = 0.02] significantly more than nonexercise groups. However, there were no significant differences in insulin resistance. CONCLUSIONS: These results provide evidence of the effects of different exercise interventions as part of a healthy lifestyle for reducing intrahepatic lipids and markers of glucose dysmetabolism. PROSPERO Registration: CRD42025639421.