Metabolic Dysfunction-Associated Steatotic Liver Disease in Childhood: From Disease Heterogeneity to Personalized Care.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the most common chronic liver disease in childhood, paralleling the global increase in pediatric obesity and metabolic dysfunction. Once considered a benign condition, pediatric MASLD is now recognized as a heterogeneous and potentially progressive disease that may advance from simple steatosis to steatohepatitis, fibrosis, and, rarely, cirrhosis, with lifelong hepatic and cardiometabolic consequences. Its pathogenesis is multifactorial, involving insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, genetic and epigenetic susceptibility, environmental factors, and alterations in the gut microbiome. Most affected children are asymptomatic, and diagnosis is often prompted by elevated liver enzymes or incidental imaging findings. Noninvasive tools, including ultrasonography, elastography, serum biomarkers, and emerging multi-omics approaches, are improving disease detection and risk stratification, although liver biopsy remains the reference standard in selected cases. Lifestyle modification, including dietary optimization, increased physical activity, and gradual weight reduction, remains the cornerstone of management, while pharmacological therapies are still under investigation in pediatric populations. The marked variability in disease susceptibility; progression; and treatment response underscores the need for a personalized medicine approach. Integrating clinical characteristics with genomic, epigenomic, metabolomic, and microbiome data may enable early identification of high-risk children, more accurate prognostic assessment, and individualized preventive and therapeutic strategies. Early detection and multidisciplinary care involving pediatricians, hepatologists, endocrinologists, dietitians, and families may help reduce disease progression and the risk of long-term hepatic and cardiometabolic complications. This review summarizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pediatric MASLD, with a particular emphasis on precision diagnostics, biomarker discovery, and personalized therapeutic approaches. It also discusses current challenges and future directions for implementing personalized medicine to improve outcomes and reduce the lifelong burden of pediatric MASLD.