Dataset Information

Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population.

ABSTRACT: Several adult omics studies have been conducted to understand the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, the histological features of children are different from those of adults, and the onset and progression of pediatric NAFLD are not fully understood. In this study, we aimed to evaluate the metabolome profile and metabolic pathway changes associated with pediatric NAFLD to elucidate its pathophysiology and to develop machine learning-based NAFLD diagnostic models. We analyzed the metabolic profiles of healthy control, lean NAFLD, overweight control, and overweight NAFLD groups of children and adolescent participants (N = 165) by assessing plasma samples. Additionally, we constructed diagnostic models by applying three machine learning methods (ElasticNet, random forest, and XGBoost) and multiple logistic regression by using NAFLD-specific metabolic features, genetic variants, and clinical data. We identified 18 NAFLD-specific metabolic features and metabolic changes in lipid, glutathione-related amino acid, and branched-chain amino acid metabolism by comparing the control and NAFLD groups in the overweight pediatric population. Additionally, we successfully developed and cross-validated diagnostic models that showed excellent diagnostic performance (ElasticNet and random forest model: area under the receiver operating characteristic curve, 0.95). Metabolome changes in the plasma of pediatric patients with NAFLD are associated with the pathophysiology of the disease and can be utilized as a less-invasive approach to diagnosing the disease.

SUBMITTER: Chae W

PROVIDER: S-EPMC9503976 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population.

Chae Woori W Lee Kyung Jae KJ Huh Ki Young KY Moon Jin Soo JS Ko Jae Sung JS Cho Joo-Youn JY

Metabolites 20220919 9

Several adult omics studies have been conducted to understand the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, the histological features of children are different from those of adults, and the onset and progression of pediatric NAFLD are not fully understood. In this study, we aimed to evaluate the metabolome profile and metabolic pathway changes associated with pediatric NAFLD to elucidate its pathophysiology and to develop machine learning-based NAFLD diagnostic models ...[more]

PMID: 36144285

Similar Datasets

Project description:BACKGROUND:Prevalence of nonalcoholic fatty liver disease (NAFLD) and rate of advanced fibrosis among individuals with metabolic syndrome (MetS) and its individual metabolic abnormalities needs better understanding in the United States population. We aim to study these by using a large United States population database, the Third National Health and Nutrition Examination Survey (NHANES III). METHODS:A total of 11,674 individuals were included in our study cohort. NAFLD was defined as presence of moderate to severe hepatic steatosis on liver ultrasound in absence of viral hepatitis, significant alcohol use, elevated transferrin level, and medication use leading to hepatic steatosis. Advanced fibrosis among those with NAFLD was determined using noninvasive method, the NAFLD fibrosis score. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III definition. RESULTS:The prevalence of NAFLD among included study cohort was 18.2% (95% confidence interval, 16.5-19.9). Individuals with metabolic abnormalities demonstrated higher prevalence (MetS, 43.2%; increased waist circumference, 31.2%; impaired fasting glucose/diabetes, 41.2%; high triglyceride level, 34.7%; low high-density lipoprotein, 27.8%; high blood pressure, 29.2%). The individuals with MetS had significantly higher NAFLD prevalence compared with controls (adjusted odds ratio, 11.5; 95% confidence interval, 8.9-14.7). The severity of hepatic steatosis was also noted to increase with higher number of metabolic abnormalities. Among individual metabolic abnormalities, increased waist circumference, impaired fasting glucose/diabetes, high triglyceride, and low high-density lipoprotein levels were found to be independently associated with NAFLD. Individuals with impaired fasting glucose/diabetes and those with 5 metabolic abnormalities had higher rate of advanced fibrosis (18.6% and 30.3%, respectively). Prevalence of NAFLD among individuals without any metabolic abnormality was 6.1%. CONCLUSION:Prevalence of NAFLD and rate of advanced fibrosis are significantly high among individuals with metabolic abnormalities.

Project description:ObjectivesNonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome (MetS) among adults. Emerging data suggest that MetS may be associated with nonalcoholic fatty liver disease (NAFLD) in children as well. We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD.MethodsChildren and adolescents aged 6-17 years enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with clinical data obtained within 6 months of liver biopsy were included. MetS was defined as the presence of three or more of the following features as determined by application of age-adjusted normative values: central obesity, dyslipidemia, impaired fasting glucose, and elevated blood pressure. Liver biopsies were evaluated by the Pathology Committee of the NASH CRN.ResultsTwo hundred fifty four children were included in the analysis, of whom 65 (26%) met specified criteria for MetS. Among children with MetS, there is a higher proportion of females who were on average older in age and pubertal. The risk of MetS was greatest among those with severe steatosis (odds ratio (OR)=2.58 for grade 3 vs. grade 1 steatosis, P=0.001). The presence of hepatocellular ballooning was also significantly associated with MetS (OR=2.10, P=0.03). Those with advanced fibrosis (stage 3/4) had an OR for MetS of 3.21 (P=0.04) vs. those without fibrosis (stage 0). Borderline zone 1 or definite NASH patterns compared with "not NASH" were strongly associated with MetS (OR=4.44, P=0.005 and OR=4.07, P=0.002, respectively). The mean NAFLD Activity Score (NAS) was greater among children with MetS vs. those without (4.8 +/- 1.4 vs. 4.3 +/- 1.4, P=0.01). Central obesity was significantly associated with steatosis, fibrosis, hepatocellular ballooning, and NAFLD pattern. Insulin resistance was significantly associated with steatosis, fibrosis, hepatocellular ballooning, NAS, and NAFLD pattern.ConclusionsMetS is common among children with NAFLD and is associated with severity of steatosis, hepatocellular ballooning, NAS, NAFLD pattern, and the presence of advanced fibrosis. Individual MetS features, particularly central obesity and insulin resistance, were also associated with severity of NAFLD. MetS features should be considered in children with NAFLD as individually and collectively they help identify children with more advanced disease.

Dataset Information

Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population.

Publications

Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets