Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease.
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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.
SUBMITTER: Mueller NT
PROVIDER: S-EPMC7494240 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionCross-sectional data note lower levels of testosterone and sex hormone-binding globulin (SHBG) levels in men with nonalcoholic fatty liver disease (NAFLD). Whether sex hormone levels in young men are predictive of later risk of NAFLD is not known.MethodsAmong men in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults study (mean age 50; n = 837), we assessed whether testosterone and SHBG levels measured at study year 10 (median age 35 years) were associated with prevalent NAFLD at study year 25. NAFLD was defined using noncontrast abdominal computed tomography (CT) scan after excluding other causes of hepatic steatosis. The association of testosterone and SHBG with prevalent NAFLD was assessed by logistic regression.ResultsTotal testosterone levels in young men were inversely associated with subsequent prevalent NAFLD on unadjusted analysis (odds ratio [OR] 0.64, 95% confidence interval 0.53-0.7, P < 0.001), although no longer significant after adjustment for year 10 metabolic covariates as well as change in metabolic covariates from years 10 to 25 (OR 0.99, 95% confidence interval 0.76-1.27). In contrast, there was a significant inverse association of SHBG with prevalent NAFLD, independent of testosterone and metabolic covariates (OR 0.68, OR 0.51-0.92, P = 0.013). On formal mediation testing, visceral adiposity was found to explain ∼41.0% (95% confidence interval 27%-73%) of the association of lower SHBG with prevalent NAFLD.ConclusionsLower levels of SHBG in young men are associated with increase in prevalent NAFLD in middle age, independent of comprehensive metabolic risk factors. SHBG may provide a novel marker of NAFLD risk in young men.
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