Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease in children. It is known to encompass a spectrum of liver diseases, which includes simple hepatic steatosis and non-alcoholic steatohepatitis (NASH). This, in turn, can progress into fibrosis, cirrhosis, and even hepatocellular carcinoma.

In the current study, researchers compared paired liver biopsies from 122 of 139 children with NAFLD, who received placebo and standard of care lifestyle advice in two randomized clinical trials within the NASH clinical research network. Histological variations were evaluated with respect to baseline and longitudinal change in clinical variables with the help of a regression analysis.

The results divulged that at the time of participation in the trial, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver without NASH. However, borderline or definite NASH normalized in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH over a mean time period of 1.6±0.4 years. Fibrosis ameliorated in 34% of the children whereas worsened in 23% of children. Children who progressed to either definite NASH or fibrosis were 36% of the children, while both of these liver diseases occurred in 11% of the children. Any resolution in NASH or fibrosis was seen in 52%, while improvement of both occurred in 20% of children. Moreover, progression to type 2 diabetes was reported in 5% of the cohort. Various risk factors associated with the advancement to NASH and/or fibrosis were adolescent age, higher waist circumference, levels of alanine or aspartate aminotransferase, total and low density lipoprotein cholesterol at baseline, increasing level of alanine aminotransferase, glycosylated hemoglobin. In addition, deterioration to NASH and/or fibrosis in children with NAFLD was also correlated with increasing level of gamma-glutamyl transferase and development of type 2 diabetes. 

Thus, based on the above mentioned observations, it can be concluded that histological evaluation of one-third of children with NAFLD included in placebo groups of clinical trials had features of progression to NASH or fibrosis within 2 years. This advancement of disease was also associated with obesity and elevated serum levels of aminotransferases and disruption of glucose homeostasis.

Source: Xanthakos SA, Lavine JE, Yates KP, et al. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice [published online ahead of print, 2020 Jul 23]. Gastroenterology. 2020;S0016-5085(20)34996-9.