Pediatric MASLD in the precision medicine era: advances in diagnosis, prevention, and treatment

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the most clinically relevant chronic liver diseases in children and adolescents, reflecting the convergence of pediatric obesity, insulin resistance, dyslipidemia, altered glucose metabolism, and broader cardiometabolic risk. The replacement of non-alcoholic fatty liver disease (NAFLD) with MASLD represents a substantive conceptual shift, moving the field away from an exclusion-based and potentially stigmatizing definition toward a pathophysiologically grounded framework centered on metabolic dysfunction. This transition is particularly important in pediatric hepatology, where steatotic liver disease is rarely defined by alcohol exposure and is more commonly embedded within complex developmental, familial, behavioral, genetic, and socioeconomic determinants of metabolic health. Although pediatric MASLD is often discussed as part of the obesity epidemic, its clinical heterogeneity indicates that body mass index alone is insufficient to capture disease risk, severity, or prognosis. Recent evidence suggests that children with MASLD may be stratified into distinct metabolic and inflammatory phenotypes, supporting a move from uniform management toward risk-adapted and phenotype-informed care. This review synthesizes current advances in the diagnosis, prevention, and treatment of pediatric MASLD, with emphasis on precision medicine as a framework for integrating clinical, biochemical, imaging, genetic, lifestyle, and social determinants into individualized care pathways. Current management remains anchored in lifestyle intervention and multidisciplinary cardiometabolic risk reduction, while important gaps persist in pediatric-specific non-invasive diagnostics, fibrosis risk prediction, longitudinal monitoring, and MASLD-targeted pharmacotherapy. A precision medicine approach may improve early identification of high-risk children, guide intensity of follow-up, inform therapeutic prioritization, and ultimately reduce liver-related and cardiometabolic complications across the life course.