Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease.

Challenge

Alanine aminotransferase (ALT) is widely used as a surrogate marker for liver injury in pediatric NAFLD, but the natural variability of ALT over time in children had not been characterized in a real-world cohort, creating uncertainty about how to interpret ALT fluctuations as endpoints or enrollment criteria in trials.

Solution

The TARGET-NASH pediatric cohort was analyzed to model longitudinal ALT trajectories and identify patient characteristics associated with ALT transitions, providing the first real-world characterization of ALT stability patterns in children with NAFLD.

Impact

Establishing that ALT trajectories in pediatric NAFLD are relatively stable over time, and characterizing predictors of change, informs trial endpoint design and enrollment criteria for pediatric NAFLD drug development programs, reducing endpoint noise and improving signal detection.