Gender Differences in Non-Alcoholic Fatty Liver Disease in Obese Children and Adolescents: A Large Cross-sectional Study

Abstract Objective: Previous studies have reported sex differences in non-alcoholic fatty liver disease (NAFLD) in adults; however, little is known in children and adolescents. This study aims to examine their NAFLD prevalence and investigate the relationship between sex hormones and NAFLD. Method: 2999 Chinese obese patients aged 2-18 years were included in the study. Liver ultrasound, anthropometry, blood test, and oral glucose tolerance test were performed. We examined the prevalence of NAFLD by sex, age, and Tanner stages. Regression model and principal component factor analysis were used. Results: The prevalence of NAFLD increased with age in both sexes and the gender difference appeared before puberty. The prevalence in boys tended to be stable at the age of 11 years, whereas the girls reached the peak temporarily. NAFLD prevalence was positively associated with estradiol in boys (p = 0.011), but the opposite trend was observed in girls (P = 0.031). Testosterone levels decreased with the increase of NAFLD prevalence (P < 0.001). Luteinizing hormone and prolactin were inversely associated with NAFLD prevalence in boys and girls, respectively. Results from the principal component analysis showed that sex hormones levels and abdominal obesity were important risk factors for the prevalence of NAFLD in obese children (P<0.001). Conclusion: The notable difference in NAFLD prevalence between genders in obese children starts in early childhood. The difference arises long before puberty onset and tends to stabilize during late adolescence. Sex hormones are associated with NAFLD prevalence and are influenced by the Tanner stages and fat distribution.