The Effects of Exercise in Adults with MASLD and Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Metabolic dysfunction-associated fatty liver disease (MASLD) was reclassified from non-alcoholic fatty liver disease (NAFLD) in 2020 following international consensus, to more accurately reflect its systemic metabolic pathogenesis. It is defined as hepatic lipid accumulation (≥5% of hepatocytes showing steatosis) in the absence of a history of excessive alcohol consumption (more than 30 g per day for men and more than 20 g per day for women) or other causative factors such as viral hepatitis or hepatotoxic drugs. This disease is one of the major global public health issues. Epidemiological studies estimate that the global prevalence in the general adult population is approximately 25%–30%, rising to 69.99% in overweight adults and as high as 75.27% in obese adults. The progressive features of MASLD often lead to metabolic comorbidities (including type 2 diabetes mellitus, dyslipidemia, and hypertension) and clinically significant hepatic complications (e.g., nonalcoholic steatohepatitis [NASH], hepatic fibrosis), which collectively result in a significant reduction in the patient's health-related quality of life and an increased risk of death. In clinical studies, NASH is the most severe subtype of MASLD, with data showing that 20.27% of overweight patients with MASLD and 21.60% of obese patients with MASLD develop clinically significant fibrosis (stage F2-4), and 6.65% of overweight patients and 6.85% of obese patients progress to advanced fibrosis (stage F3 -4 stage) - and patients with advanced fibrosis have a 10%-25% risk of developing cirrhosis and hepatocellular carcinoma within 8-14 years. Therefore, some clinicians recommend lifestyle interventions (such as exercise) as first-line interventions to improve MASLD-related outcomes in such patients. However, exercise interventions for MASLD are heterogeneous in terms of modality (aerobic exercise, resistance exercise, high-intensity interval training [HIIT], combined aerobic-resistance exercise), and most of the available studies lack head-to-head comparisons between different exercise modalities, making it difficult to identify the most effective type of exercise for a given outcome. It has been shown that although both aerobic and resistance exercise reduce hepatic steatosis, resistance exercise achieves similar benefits with lower energy expenditure and percentage of maximal oxygen uptake (%VO₂max), which may improve feasibility in patients with poorer cardiorespiratory fitness. However, the relative effectiveness of HIIT and combined exercise compared to single-modality exercise remains unclear, and there is inconsistency in the effects of exercise on key outcomes (e.g., waist circumference, triglycerides, alanine aminotransferase) in overweight/obese MASLD populations. The use of exercise interventions in the management of overweight/obese adults with MASLD has raised significant clinical concerns regarding the “optimal prescription,” prompting the scientific community to increase research on the comparative effectiveness of different exercise modalities. However, these studies have not been comprehensively and systematically integrated - traditional two-by-two meta-analyses are unable to integrate indirect evidence between interventions, making it difficult to rank the effectiveness of different exercise modalities. The present network meta-analysis was able to simultaneously compare the effectiveness of four exercise intervention modalities (aerobic exercise, resistance training, high-intensity interval training, and combined aerobic-resistance exercise) by integrating direct and indirect evidence from a network of randomized controlled trials. The primary objective of this study was to assess the effectiveness of these exercise modalities in improving anthropometry (body weight, body mass index, waist circumference, body fat percentage), blood glucose (fasting glucose), blood lipid (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), and hepatic function indices (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase) in order to provide evidence-based guidance for clinical exercise prescription.