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Nonalcoholic Fatty Liver Disease A Challenge for Pediatricians

Valerio Nobili, MD1; Naim Alkhouri, MD2; Anna Alisi, PhD1; Claudia Della Corte, MD1; Emer Fitzpatrick, MD3; Massimiliano Raponi, MD1; Anil Dhawan, MD3
[+] Author Affiliations
1Hepato-Metabolic Disease Unit, Bambino Gesù Children’s Hospital, Italian Scientific Institute for Research and Care, Rome, Italy
2Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic Children’s Medical Center, Cleveland, Ohio
3Paediatric Liver, Gastrointestinal, and Nutrition Centre, King’s College London School of Medicine, King’s College Hospital, London, England
JAMA Pediatr. 2015;169(2):170-176. doi:10.1001/jamapediatrics.2014.2702.
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Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is considered the most common form of chronic liver disease in children. Several factors contribute to NAFLD development, including race/ethnicity, genetic factors, environmental exposures, and alterations in the gut microbiome. The histologic spectrum of NAFLD ranges from simple steatosis to the more aggressive nonalcoholic steatohepatitis (NASH). Fibrosis and eventually cirrhosis can develop from NAFLD during childhood. Diagnosing advanced disease is challenging and may require a liver biopsy, highlighting the urgent need for reliable, noninvasive markers of disease severity. The mainstay of treatment for NAFLD remains lifestyle modifications and weight loss. Probiotics and ω-3 fatty acids may ameliorate disease progression. Recent data have suggested that vitamin E may be considered as a NASH-specific therapy in children, and there are several ongoing human studies evaluating different therapeutic targets for NAFLD. We provide an up-to-date review of the risk factors, diagnosis, and treatment to manage this common disease in children.

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Figure 1.
Risk Factors Associated With the Pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD)

IL-6 indicates interleukin 6; INSIG, insulin-induced gene; KLF-6, Krüppel-like factor; PNPLA3, patatinlike phospholipase domain–coding protein; PUFA, polyunsaturated fatty acid; SNPs, single-nucleotide polymorphisms; and TNF, tumor necrosis factor.

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Figure 2.
Proposed Mechanism for the Beneficial Effects of Docosahexaenoic Acid (DHA)

During the development of nonalcoholic fatty liver disease (NAFLD), G protein–coupled receptor (GPR120) expressed in liver resident cells may activate the transcription of proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukins (IL-6 and IL-1β), via phosphorylated nuclear factor–κB (pNF-κB). Administration of DHA may inhibit this process.

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