Predictive, non-invasive tools are needed to monitor key features of nonalcoholic fatty liver disease (NAFLD) in children that relate to improvement in liver histology. The purpose of this study was to evaluate the relationship between liver chemistries and liver histology using data from the CyNCh clinical trial. This study included 146 children. Improvement in liver histology, defined as decrease in NAFLD Activity Score ≥ 2 points without worsening of fibrosis, occurred in 43 participants (30%). There were 46 participants with borderline zone 1 nonalcoholic steatohepatitis (NASH) at baseline, with resolution in 28% (12/46). Multivariate models were constructed using baseline and change in ALT, AST, and GGT at 52 weeks, for improvement in 1) liver histology primary outcome 2) borderline zone 1 NASH, and 3) fibrosis. For improvement in histology, the model (p < 0.0001) retained baseline and change in GGT (AUROC 0.79; 95% CI 0.71 - 0.87). For borderline zone 1 NASH, the model (p = 0.0004) retained baseline and change in ALT (AUROC 0.80; 95% CI 0.67 - 0.93). For fibrosis, the model (p<0.001) retained baseline and change in ALT (AUROC 0.80, 95% CI 0.67-0.93). Additional clinical parameters were added to the models using Akaike's Information Criteria selection, and significantly boosted performance: improvement in histology with AUROC of 0.89 (95% CI 0.82 - 0.95), borderline zone 1 NASH with AUROC of 0.91 (95% CI 0.83 - 0.99) and fibrosis with AUROC of 0.89 (95% CI 0.82-0.94). Models were validated using data from the TONIC trial. Conclusion: In children with NAFLD, dynamic changes in serum ALT and GGT are associated with change in liver histology and appear to be powerful indicators of histologic response.