Pediatric MASLD tied to early morbidity

Metabolic dysfunction–associated steatotic liver disease (MASLD) in children is increasingly common worldwide and is associated with early fibrosis progression, incident type 2 diabetes, major adverse liver outcomes, and increased mortality in young adulthood, according to a comprehensive clinical review published in the Journal of Hepatology.

Drawing from global epidemiologic datasets, longitudinal cohort studies, biopsy series, and recent therapeutic trials, researchers in four European countries reported that pediatric MASLD now affects an estimated 7.6% of children aged 2 to 19 years in the general population, with prevalence rising to 39.2% in children with overweight and 52.5% in those with obesity. In adolescents aged 15 to 19 years, global prevalence was 4.7%, with the highest regional burden in the Middle East and North Africa (up to 18.4% in Egypt). Boys are disproportionately affected (median 5.8% vs 3.5% in girls).

Short-term natural history data from the NASH Clinical Research Network indicate that over 2 years, 20% to 25% of children experienced fibrosis progression, worsening NAFLD activity score, or rising alanine aminotransferase (ALT) and gamma-glutamyl transferase levels, whereas 25% to 50% improved. A 5% increase in body mass index (BMI) z score was associated with worsening disease (odds ratio [OR], 1.3; 95% CI, 1.1-1.5), as was a 5% increase in total cholesterol (OR, 1.3; 95% CI, 1.2-1.5). In a Dutch cohort followed for 10 years, 16% showed fibrosis progression and 6% had advanced fibrosis by enhanced liver fibrosis testing in young adulthood.

Longer-term outcomes are concerning. In a US cohort of more than 1,000 children with MASLD who were followed for a mean of 8.5 years, cumulative cirrhosis incidence was 4.7%, and the standardized mortality rate was 40-fold higher than in matched controls; 1.6% died, nearly half from liver-related causes. In a Swedish study, biopsy-confirmed NAFLD diagnosed before age 25 was associated with increased liver-related mortality (adjusted hazard ratio [aHR], 16.5; 95% CI, 2.8-98.4). A separate Swedish study found that childhood obesity conferred a doubled risk of major adverse liver outcomes by early adulthood, with cumulative prevalence of 1.1% at age 40.

The authors found that metabolic comorbidity is bidirectional in nature. A multicenter North American cohort of 892 children with biopsy-proven NAFLD found that 6.6% had type 2 diabetes at baseline; over 3.8 years, 10.9% developed diabetes, which translated to an incidence rate of 3,000 new cases per 100,000 person-at-risk years. Female sex, higher BMI z score, and greater baseline steatosis and fibrosis (hazard ratio, 1.3 each) independently predicted incident diabetes. In Swedish registry data, children with obesity and MASLD had the highest diabetes incidence (131 per 10,000 person-years; hazard ratio, 2.7), rising to 9.0 with intermediate hyperglycemia.

The authors note that no pharmacologic therapy is approved specifically for pediatric MASLD, and they emphasized the need for validated noninvasive tests and pediatric-focused therapeutic trials. Pediatric MASLD “can be aggressive, potentially leading to clinical complications in early adulthood and a high number of healthy life years lost,” they concluded.