Longitudinal response to standard of care in pediatric metabolic dysfunction-associated steatotic liver disease: Rates of improvement and worsening, and factors associated with outcomes.

Background and aims: Longitudinal outcomes in children with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear due to the absence of a standardized monitoring approach. This study aimed to (1) define improvement and worsening in children with MASLD, (2) estimate rates of improvement or deterioration with the standard of care (SOC) over 1 and 2 years, and (3) identify baseline and longitudinal factors associated with improvement or worsening.

Approach and results: Using data from 2 large randomized controlled trials, we derived definitions for composite improvement and worsening of MASLD based on associations between changes in ALT, GGT, and liver histology after 1 and 2 years. Improvement was defined as ≥40% decrease in ALT and ≥20% decrease in GGT and worsening as ≥20% increase in both ALT and GGT. We applied definitions to a cohort of 440 children with MASLD. After 1 year of SOC, 22% of children with MASLD showed improvement, increasing to 31% after 2 years. However, 20% showed worsening after both 1 and 2 years despite receiving SOC. Logistic regression analysis, employing stepwise model selection, identified changes in body mass index z-score and cholesterol to be most associated with improvement or deterioration.

Conclusions: This study developed criteria for improvement and worsening in children with MASLD over 1 and 2 years of follow-up. With SOC, over one-quarter of children are likely to improve while one-fifth of children are likely to worsen. Targeting interventions that affect body mass index and lipid parameters may help improve MASLD over time.