Comparative efficacy of drugs with different mechanistic pathways/targets in the treatment of pediatric NAFLD: evidence from a Bayesian network meta-analysis.

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].