https://pubmed.ncbi.nlm.nih.gov/32712103/ NAFLD

Gastroenterology. 2020 Jul 23;S0016-5085(20)34996-9.
doi: 10.1053/j.gastro.2020.07.034.Online ahead of print.

Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

Stavra A Xanthakos 1, Joel E Lavine 2, Katherine P Yates 3, Jeffrey B Schwimmer 4, Jean P Molleston 5, Philip Rosenthal 6, Karen F Murray 7, Miriam B Vos 8, Ajay K Jain 9, Ann O Scheimann 10, Tamir Miloh 11, Mark Fishbein 12, Cynthia A Behling 13, Elizabeth M Brunt 14, Arun J Sanyal 15, James Tonascia 3, NASH Clinical Research Network
PMID: 32712103
DOI: 10.1053/j.gastro.2020.07.034

Abstract

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth.

Methods: We compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13±3 years; age range, 8-17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis.

Results: At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean time period of 1.6±0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH or in fibrosis occurred in 36% of the children, and both occurred in 11% of the children. Any improvement in NASH or fibrosis occurred in 52%, and both occurred in 20% of children. Type 2 diabetes developed in 5% of the cohort. Any progression to NASH and/or fibrosis were associated with adolescent age, higher waist circumference, levels of alanine or aspartate aminotransferase, total and low density lipoprotein cholesterol at baseline, increasing level of alanine aminotransferase, hemoglobin A1C (P<.05). Progression to NASH and/or fibrosis were also associated with increasing level of gamma-glutamyl transferase and development of type 2 diabetes (P<.01). Increasing level of gamma-glutamyl transferase also associated with reduced odds of any improvement (P=.003).
Conclusions: One-third of children with NAFLD enrolled in placebo groups of clinical trials had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.