Updates on paediatric MASLD: insights from an endocrine lens.

Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in children and adolescents worldwide and is increasing alongside rising rates of paediatric obesity and type 2 diabetes. Paediatric MASLD most often arises in the setting of obesity and metabolic dysfunction but can occur without obesity and is influenced by early life exposures, genetics and environmental factors. Paediatric MASLD and youth-onset type 2 diabetes are tightly linked given the shared and bidirectional pathophysiological mechanisms. Hepatic steatosis often develops early in the course of insulin resistance, even in preschool-age children. Epidemiology in children varies by sex and ancestry and carries major prognostic implications, with a higher MASLD prevalence in male and Hispanic youth, more severe liver disease when MASLD coexists with impaired glucose tolerance or type 2 diabetes, and an alarming increased risk of mortality in late childhood and young adulthood. Paediatric MASLD is distinct from adult disease, with 20-25% of affected youth demonstrating clinically significant fibrosis on histology, distinct periportal (zone 1) patterns unique to childhood disease, and more severe liver histology in those with impaired glucose tolerance or diabetes. Early life determinants, such as maternal obesity and diabetes, are associated with childhood steatosis beginning early in life. Further, puberty represents a critical window of vulnerability, as physiological insulin resistance, sex-specific effects of androgens, and obesity-related metabolic stress drive sharp increases in both MASLD and youth-onset type 2 diabetes, with distinct sex differences in prevalence and severity. Current management for MASLD in paediatrics is evolving, relying primarily on lifestyle modification and targeted screening but with emerging evidence supporting the benefits of glucagon-like peptide-1 receptor agonists and bariatric surgery in selected youth with obesity, type 2 diabetes and related comorbidities, underscoring the urgent need for paediatric-specific therapeutic trials.