TY - JOUR
T1 - Alanine aminotransferase as a monitoring biomarker in children with nonalcoholic fatty liver disease
T2 - A secondary analysis using tonic trial data
AU - Arsik, Idil
AU - Frediani, Jennifer K.
AU - Frezza, Damon
AU - Chen, Wen
AU - Ayer, Turgay
AU - Keskinocak, Pinar
AU - Jin, Ran
AU - Konomi, Juna V.
AU - Barlow, Sarah E.
AU - Xanthakos, Stavra A.
AU - Lavine, Joel E.
AU - Vos, Miriam B.
N1 - Funding Information:
NIH R03 DK096157, R21 HD089056, PD303567-SC105312 (Vos). The NASH CRN Clinical Center NIH U01DK061737 and U01DK061730. These agencies did not have any role in this study. The TONIC Study was conducted by the NASH CRN Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the TONIC reported here were supplied by the NIDDK Central Repositories. This manuscript was not prepared in collaboration with Investigators of the TONIC study and does not necessarily reflect the opinions or views of the TONIC study, the NIDDK Central Repositories, or the NIDDK.
Funding Information:
Acknowledgments: NIH R03 DK096157, R21 HD089056, PD303567-SC105312 (Vos). The NASH CRN Clinical Center NIH U01DK061737 and U01DK061730. These agencies did not have any role in this study. The TONIC Study was conducted by the NASH CRN Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the TONIC reported here were supplied by the NIDDK Central Repositories. This manuscript was not prepared in collaboration with Investigators of the TONIC study and does not necessarily reflect the opinions or views of the TONIC study, the NIDDK Central Repositories, or the NIDDK.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/6
Y1 - 2018/6
N2 - Background: Validated noninvasive biomarkers to assess treatment response in pediatric nonalcoholic fatty liver 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.
AB - Background: Validated noninvasive biomarkers to assess treatment response in pediatric nonalcoholic fatty liver 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.
KW - ALT
KW - Fibrosis
KW - NASH
KW - Pediatrics
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U2 - 10.3390/children5060064
DO - 10.3390/children5060064
M3 - Article
C2 - 29799476
AN - SCOPUS:85065507135
SN - 2227-9067
VL - 5
JO - Children
JF - Children
IS - 6
M1 - 64
ER -