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 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 standard of care (SOC) over one and two years, and 3) identify baseline and longitudinal factors associated with improvement or worsening.

Approach and results: Using data from two 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 one and two 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 one year of SOC, 22% of children with MASLD showed improvement, increasing to 31% after two years. However, 20% showed worsening after both one and two years despite receiving SOC. Logistic regression analysis, employing stepwise model selection, identified changes in body mass index (BMI) z-score and cholesterol to be most associated with improvement or deterioration.

Conclusion: This study developed criteria for improvement and worsening in children with MASLD over one and two 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 BMI and lipid parameters may help improve MASLD over time.