TY - JOUR
T1 - Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease
AU - Mueller, Noel T.
AU - Liu, Tiange
AU - Mitchel, Elana B.
AU - Yates, Katherine P.
AU - Suzuki, Ayako
AU - Behling, Cynthia
AU - Lavine, Joel E.
N1 - Funding Information:
National Institutes of Health (NIH) U01DK61734, NIH U01DK61734-11(S1), and NIH 5UL1TR001873 to J.E.L. (PI). Also, NIH U01DK061730, NIH U24DK061730 to the Data Coordinating Center at Johns Hopkins Bloomberg School of Public Health.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - Estrogen
KW - Histology
KW - Progesterone
KW - Puberty
KW - Sex hormone binding globulin
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=85091191863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091191863&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgaa574
DO - 10.1210/clinem/dgaa574
M3 - Article
C2 - 32840311
AN - SCOPUS:85091191863
VL - 105
SP - 1
EP - 9
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -