Abstract
Context
Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD.
Objective
To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD.
Design
Baseline assessment of longitudinal cohorts and randomized clinical trials.
Setting
Nonalcoholic Steatohepatitis Clinical Research Network.
Patients
Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States.
Main Outcome Measures
We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression.
Results
Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features.
Conclusions
Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.
The Association Between Nonalcoholic Fatty Liver Disease and Metabolic Abnormalities in The United States Population