Key result
Energy-modulating therapies increase pediatric NAFLD steatosis improvement ~3-fold over placebo.
Why the study?
Do pharmacological interventions modulating specific mechanistic pathways improve hepatic steatosis in pediatric NAFLD patients?
Meta-Analysis (n=1,582)
Do pharmacological interventions modulating specific mechanistic pathways improve hepatic steatosis in pediatric NAFLD patients?
Answers are grounded in this paper and cite their sources.
Drugs modulating energy, inflammation, and gut microbiota are more effective than placebo in improving hepatic steatosis in pediatric NAFLD, with energy modulators showing optimal benefits for liver enzymes and metabolic parameters.
Objective Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in children and adolescents, and there is no defined treatment for this condition. A network meta-analysis (NMA) was conducted to examine the comparative efficacy of specific mechanism pathways of drugs to achieve improvements in hepatic steatosis in pediatric NAFLD patients. Methods Randomized controlled trials regarding pharmacological interventions for pediatric NAFLD patients were obtained. Treatments were classified into energy, inflammation, fibrosis, and gut microbiota modulators. The primary outcome was an improvement in hepatic steatosis, and the secondary outcomes included changes in liver enzymes, lipid profile, and metabolic parameters. Direct meta-analysis and NMA with Bayesian random effects were performed for the extracted data, respectively. Results Nineteen RCTs that met the eligibility criteria were identified for this analysis, involving a total of 1,582 pediatric NAFLD patients confirmed by ultrasound or biopsy. Treatment modulating energy (Relative risk (RR): 3.32; 95% Credible intervals (CrI): 1.52–8.26; P < 0.05), inflammation (RR: 2.33; 95% CrI: 1.09–5.27; P < 0.05) and gut microbiota (RR: 4.60; 95% CrI: 1.42–15.69; P < 0.05) were all more effective than placebo in improving hepatic steatosis. Further analysis of secondary outcomes indicated that treatments modulating energy were the optimal agents for reducing serum alanine aminotransferase (ALT) levels (surface under the cumulative ranking curve (SUCRA) = 86.20%), decreasing triglyceride (TG) contents (SUCRA = 91.77%), increasing high-density lipoprotein cholesterol (HDL-C) levels (SUCRA = 94.29%), and improving homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA = 88.01%). Treatments modulating gut microbiota were the most effective agents for reducing BMI (SUCRA = 96.25%) in pediatric NAFLD patients. Conclusion This NMA revealed the relative advantages of drugs that modulate energy in the treatment of pediatric NAFLD, potentially serving as a valuable guide for optimizing drug development and selecting agents for combination therapies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier [CRD42023417431].
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Wang et al. (2026) conducted a meta-analysis in pediatric NAFLD (n=1,582). Pharmacological interventions (energy, inflammation, fibrosis, and gut microbiota modulators) vs. placebo was evaluated on improvement in hepatic steatosis (RR 3.32, 95% CI 1.52-8.26, p=<0.05). Treatments modulating energy (RR 3.32; 95% CrI 1.52-8.26), inflammation, and gut microbiota were more effective than placebo in improving hepatic steatosis in pediatric NAFLD.
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