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Multi-Modality, Multi-Dimensional Characterization of Pediatric Non-Alcoholic Fatty Liver Disease.

ABSTRACT: Non-alcoholic fatty liver disease is a multifaceted disease that progresses through multiple phases; it involves metabolic as well as structural changes. These alterations can be measured directly or indirectly through blood, non-invasive imaging, and/or tissue analyses. While some studies have evaluated the correlations between two sets of measurements (e.g., histopathology with cross-sectional imaging or blood biomarkers), the interrelationships, if any, among histopathology, clinical blood profiles, cross-sectional imaging, and metabolomics in a pediatric cohort remain unknown. We created a multiparametric clinical MRI-histopathologic NMR network map of pediatric NAFLD through multimodal correlation networks, in order to gain insight into how these different sets of measurements are related. We found that leptin and other blood markers were correlated with many other measurements; however, upon filtering out the blood biomarkers, the network was decomposed into three independent hubs centered around histopathological features, each with associated MRI and plasma metabolites. These multi-modality maps could serve as a framework for characterizing disease status and progression and could potentially guide medical interventions.

SUBMITTER: Jamshidi N

PROVIDER: S-EPMC10456937 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Multi-Modality, Multi-Dimensional Characterization of Pediatric Non-Alcoholic Fatty Liver Disease.

Jamshidi Neema N Feizi Alborz A Sirlin Claude B CB Lavine Joel E JE Kuo Michael D MD

Metabolites 20230808 8

Non-alcoholic fatty liver disease is a multifaceted disease that progresses through multiple phases; it involves metabolic as well as structural changes. These alterations can be measured directly or indirectly through blood, non-invasive imaging, and/or tissue analyses. While some studies have evaluated the correlations between two sets of measurements (e.g., histopathology with cross-sectional imaging or blood biomarkers), the interrelationships, if any, among histopathology, clinical blood pr ...[more]

PMID: 37623872

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Project description:One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease (NAFLD), which is the most common form of liver disease in children. NAFLD is defined by hepatic fat infiltration > 5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake, viral, autoimmune and drug-induced liver disease. It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, which, in turn, can evolve into cirrhosis and end stage liver disease. Obesity and insulin resistance are the main risk factors for pediatric NAFLD. In fact, NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome, prediabetes and type 2 diabetes mellitus (T2D). In particular, it has been clearly shown in obese youth that the prevalence of metabolic syndrome, pre-diabetes and type 2 diabetes increases with NAFLD severity progression. Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition. Recently, a non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene (PNPLA3), has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children. Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein. The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes, is aimed at acting upon specific targets involved in the pathogenesis. There are some therapeutic approaches that are being studied in children. This article reviews the current knowledge regarding the pediatric fatty liver disease, the new insights and the future directions.

Dataset Information

Multi-Modality, Multi-Dimensional Characterization of Pediatric Non-Alcoholic Fatty Liver Disease.

Publications

Multi-Modality, Multi-Dimensional Characterization of Pediatric Non-Alcoholic Fatty Liver Disease.

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