TY - JOUR
T1 - High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery
AU - Xanthakos, Stavra A.
AU - Jenkins, Todd M.
AU - Kleiner, David E.
AU - Boyce, Tawny W.
AU - Mourya, Reena
AU - Karns, Rebekah
AU - Brandt, Mary L.
AU - Harmon, Carroll M.
AU - Helmrath, Michael A.
AU - Michalsky, Marc P.
AU - Courcoulas, Anita P.
AU - Zeller, Meg H.
AU - Inge, Thomas H.
N1 - Publisher Copyright:
© 2015 AGA Institute.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Background & Aims Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. Methods We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m2). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. Results NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P <.01), and white blood cell count (P =.04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. Conclusions More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.
AB - Background & Aims Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. Methods We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m2). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. Results NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P <.01), and white blood cell count (P =.04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. Conclusions More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.
KW - Inflammation
KW - Microarray
KW - Pediatric
KW - Severe Obesity
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U2 - 10.1053/j.gastro.2015.05.039
DO - 10.1053/j.gastro.2015.05.039
M3 - Article
C2 - 26026390
AN - SCOPUS:84939824712
SN - 0016-5085
VL - 149
SP - 623e8-634.e8
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -