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

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 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. Intra-operative 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 y old; median body mass index [BMI], 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) was observed in 18% of liver biopsies and stage 3 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 (ALT), 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 ALT and cardio-metabolic risk factors, but not BMI. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.

The initiation of metabolic inflammation in childhood obesity

“…Beyond these changes in circulating biomarkers, tissuespecific inflammation in obese children parallels what is seen in obese adults. NAFLD is present in 59% of adolescents referred for bariatric surgery, with 10% of these showing evidence of nonalcoholic steatohepatitis (NASH) (89). Severity of NAFLD in this cohort correlated with wbc count, and liver samples from adolescents with NASH had increased expression of genes involved in macrophage chemotaxis.…”

The Progression and Natural History of Pediatric Nonalcoholic Fatty Liver Disease

“…Adolescents selected for extreme obesity may be biologically different that children with NAFLD who are seen in gastroenterology clinics. In the multi-center Teen LABS Study of adolescents undergoing bariatric surgery, 148 had intraoperative liver biopsies and the prevalence of NAFLD in this cohort was 59%, with only 10% of those with NAFLD having definite NASH and 0.7% having advanced fibrosis [22]. …”

Role of bariatric surgery in treatment of non-alcoholic fatty liver disease

“…10 However, Results from different studies show that the prevalence of NAFLD varies between 16.7% and 96% in morbidly obese patients subjected to bariatric surgery. [10][11][12][13][14][15][16][17][18][19][20][21][22] The wide range of NAFLD prevalence depends on the biochemical criteria and the method sensitivity used to detect NAFLD. 8,23 Furthermore, NASH, as a progressive manifestation of NAFLD, occurs in 7.3% to 98% of such patients.…”

“…8,23 Furthermore, NASH, as a progressive manifestation of NAFLD, occurs in 7.3% to 98% of such patients. 10,12,13,17,18,[20][21][22][24][25][26][27][28][29][30] The study which reported NASH in 98% of their patients, indicated that the mean super obese state (Mean BMI 52.8 kg ⁄m 2 ) in their population is the reason of high NASH prevalence. 30 Another study concluded that the differences in NASH prevalence can be explained by the histological criteria used to diagnose NASH.…”