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

Abstract

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.

Keywords: body weight; children; cholesterol; diet; exercise.

Figure 1.

Bar graph depicting percentage change in ALT and GGT, according to changes in histologic outcomes for the two cohorts, CyNCh and TONIC, included in the development stage. Analyzing the data for these two studies together, in those children with histologic improvement, the weighted average change in ALT was −37.3%, and change in GGT was −19.7%. For children with histologic worsening, the weighted average change in ALT was 14.1%, and change in GGT was 13.9 %. *P values for analysis of variance tests (ANOVA) for differences in the means across groups defined by change.

Figure 2.

Forest plots displaying odds ratios (ORs) and 95% confidence intervals (CIs) for baseline and longitudinal factors associated with improvement and worsening in MASLD at one and two years of follow-up. Composite improvement was defined as at least a 40% decrease in ALT and a 20% decrease in GGT, while composite worsening required a 20% increase in both ALT and GGT. Each plot presents adjusted ORs for individual features for each of four models. Separate models were generated for improvement and worsening at one and two years, with age and sex included as covariates.