High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery - PubMed (original) (raw)

Observational Study

. 2015 Sep;149(3):623-34.e8.

doi: 10.1053/j.gastro.2015.05.039. Epub 2015 May 28.

Todd M Jenkins 2, David E Kleiner 3, Tawny W Boyce 4, Reena Mourya 5, Rebekah Karns 6, Mary L Brandt 7, Carroll M Harmon 8, Michael A Helmrath 2, Marc P Michalsky 9, Anita P Courcoulas 10, Meg H Zeller 11, Thomas H Inge 2; Teen-LABS Consortium

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Observational Study

High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery

Stavra A Xanthakos et al. Gastroenterology. 2015 Sep.

Abstract

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/m(2)). 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.

Trial registration: ClinicalTrials.gov NCT00474318.

Keywords: Inflammation; Microarray; Pediatric; Severe Obesity.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Flow of Teen-LABS study participants excluded from and retained in final analysis cohort.

Figure 2

Figure 2

Panel A

: Distribution of NAFLD and NASH, including subtypes of borderline NASH.

Panel B

: Prevalence and distribution of fibrosis in the cohort. Stage 1 fibrosis was most frequent, predominantly stage 1c (periportal only), followed by stage 1a (mild zone 3 only) and stage 1b (moderate zone 3 only). Stage 2 (mild/moderate zone 3 and periportal fibrosis) and stage 3 (bridging) were rare. No participants had stage 4 (cirrhosis).

Figure 2

Figure 2

Panel A

: Distribution of NAFLD and NASH, including subtypes of borderline NASH.

Panel B

: Prevalence and distribution of fibrosis in the cohort. Stage 1 fibrosis was most frequent, predominantly stage 1c (periportal only), followed by stage 1a (mild zone 3 only) and stage 1b (moderate zone 3 only). Stage 2 (mild/moderate zone 3 and periportal fibrosis) and stage 3 (bridging) were rare. No participants had stage 4 (cirrhosis).

Figure 3

Figure 3

Panel A

: Venn diagram of genes differentially regulated between definite NASH and Not-NAFLD, and borderline NASH and Not-NAFLD. Section numbers inside red squares indicate gene sets shared between definite and borderline NASH that were used to generate the ontological network in

Panel B

. Ontological enrichments associated with gene lists built through comparison of definite NASH to borderline NASH are presented in

Panel C

. Relative expression values of genes associated with the ontologies in Panel C underwent hierarchical clustering to generate heatmaps in

Panel D

. Asterisks denote genes previously reported to be associated with severe fibrotic NASH in adults.

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