Evaluation of Quantitative Imaging Biomarkers for Early Phase Clinical Trials of Steatohepatitis in Adolescents.

Abstract

OBJECTIVES Early-phase pediatric nonalcoholic fatty liver disease (NAFLD) clinical trials are designed with non-invasive parameters to assess potential efficacy. Increasingly, these parameters include MRI-derived proton density fat fraction (PDFF) and MR elastography (MRE)-derived shear stiffness as biomarkers of hepatic steatosis and fibrosis, respectively. Understanding fluctuations in these measures is essential for calculating trial sample sizes, interpreting results, and planning clinical drug trials in children with NAFLD. Lack of such data in children comprises a critical knowledge gap. Therefore, the primary aim of this study was to assess whole-liver MRI-PDFF change in adolescents with nonalcoholic steatohepatitis (NASH) over 12 weeks. METHODS Adolescents 12-19 years with biopsy-proven NASH undergoing standard-of-care treatment were enrolled. Baseline and week-12 assessments of anthropometrics, transaminases, MRI-PDFF, and MRE-stiffness were obtained. RESULTS Fifteen adolescents were included (mean age 15.7 [SD 2.9] years). Hepatic MRI-PDFF was stable over 12 weeks (mean absolute change -0.8%, p = 0.24). Correlation between baseline and week-12 values of MRI-PDFF was high (ICC = 0.97, 95% CI 0.90 - 0.99). MRE-stiffness was stable (mean percentage change 2.7%, p = 0.44); correlation between baseline and week-12 values was moderate (ICC = 0.47; 95% CI: 0, 0.79). Changes in weight, BMI, and aminotransferases were not statistically significant. CONCLUSIONS In adolescents with NASH, fluctuations in hepatic MRI-PDFF and MRE-stiffness over 12 weeks of standard-of-care were small. These data on the natural fluctuations in quantitative imaging biomarkers can serve as a reference for interventional trials in pediatric NASH and inform the interpretation and planning of clinical trials.