Author information
1
H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA 30318, USA. idilarsik@gatech.edu.
2
Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Dr, Atlanta, GA 30322, USA. jfredia@emory.edu.
3
H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA 30318, USA. dfrezza3@gmail.com.
4
H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA 30318, USA. wchen424@gatech.edu.
5
H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA 30318, USA. ayer@isye.gatech.edu.
6
H. Milton Stewart School of Industrial & Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA 30318, USA. pinar@isye.gatech.edu.
7
Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Dr, Atlanta, GA 30322, USA. jinr@usc.edu.
8
Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Dr, Atlanta, GA 30322, USA. junakonomi@emory.edu.
9
Department of Pediatrics, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. sarah.barlow@utsouthwestern.edu.
10
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital, 3333 Burnet Ave, Cincinnati, OH 45229, USA. stavra.xanthakos@cchmc.org.
11
Department of Pediatrics, Columbia University, 3959 Broadway, New York, NY 10032, USA. jl3553@columbia.edu.
12
Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Dr, Atlanta, GA 30322, USA. mvos@emory.edu.
Abstract
BACKGROUND:
Validated noninvasive biomarkers to assess treatment response in pediatric nonalcoholic fattyliver disease (NAFLD) are lacking. We aimed to validate alanine aminotransferase (ALT), a monitoring biomarker for change in liver histology.
METHODS:
A retrospective analysis using data from the TONIC trial. NAFLD histologic assessments were defined by: Fibrosis score, NAFLD activity score (NAS), nonalcoholic steatohepatitis (NASH), and a combination of NASH resolution and fibrosis (NASH + fibrosis). Analysis was performed using classification and regression trees (CART) as well as logistic regression.
RESULTS:
Mean ALT for the child over 96 weeks and percent change of ALT from baseline to 96 weeks were significant predictors of progression of NAFLD for each histologic assessment (p < 0.001 for fibrosis score, NASH, and NASH + fibrosis and p < 0.05 for NAS). Mean ALT adjusted for age, sex and ethnicity was a better predictor for change in NASH (81.8 (11.0) ROC (receiver operating characteristic curve) mean (SD (Standard derivation))) and NASH + fibrosis (77.8 (11.2)), compared to change in NAS (63 (17.7)) and fibrosis (58.6 (11.1)).
CONCLUSION:
Mean ALT over 96 weeks is a reasonable proxy of histologic improvement of NASH and NASH + fibrosis. These findings support ALT as a valid monitoring biomarker of histologic change over time in children with NASH and fibrosis.