Purpose: Nonalcoholic fatty liver (NAFL) is a major contributor to pediatric liver disease. This review evaluated the current literature on prevalence, screening, diagnosis, and management of NAFL in children and explored recent advances in the field of pediatric NAFL.Methods: A PubMed search was performed for manuscripts describing disease burden, diagnosis, and management strategies in pediatric NAFL published within the past 15 years. Systematic reviews, clinical practice guidelines, randomized controlled trials, and cohort and caseecontrol studies were reviewed for the purpose of this article.Findings: The prevalence of NAFL in children is increasing. It is a leading cause of liver-related morbidity and mortality in children. Screening and diagnosis of NAFL in children are a challenge. Lifestyle changes and exercise are the cornerstones of the management of NAFL.Implications: Further research is needed to develop better screening and diagnostic tools for pediatric NAFL, including noninvasive diagnostics. NAFL therapeutics is another area of much-needed, ongoing research.

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Background Total Parenteral Nutrition (TPN) provides lifesaving nutritional support to patients unable to maintain regular enteral nutrition (EN). Unfortunately, cholestasis is a significant side effect affecting 20–40% of paediatric patients. While the aetiology of TPN-associated injury remains ill-defined, an altered enterohepatic circulation in the absence of gut luminal nutrient content during TPN results in major gut microbial clonal shifts, resulting in metabolic endotoxemia and systemic inflammation driving liver injury and cholestasis. Hypothesis To interrogate the role of gut microbiota, using our novel ambulatory TPN piglet model, we hypothesized that clonal reduction of bacteria in Firmicutes phylum (predominant in EN) and an increase in pathogenic Gram-negative bacteria during TPN correlates with an increase in serum lipopolysaccharide and systemic inflammatory cytokines, driving liver injury. Methods Upon institutional approval, 16 animals were allocated to receive either TPN ( n = 7) or EN only ( n = 9). The TPN group was subdivided into a low systemic inflammation (TPN-LSI) and high systemic inflammation (TPN-HSI) based on the level of serum lipopolysaccharide. Culture-independent identification of faecal bacterial populations was determined by 16S rRNA. Results Piglets on TPN, in the TPN-HSI group, noted a loss of enterocyte protective Firmicutes bacteria and clonal proliferation of potent inflammatory and lipopolysaccharide containing pathogens: Fusobacterium , Bacteroidetes and Campylobacter compared to EN animals. Within the TPN group, the proportion of Firmicutes phylum correlated with lower portal lipopolysaccharide levels ( r = −0.89). The TPN-LSI had a significantly lower level of serum bile acids compared to the TPN-HSI group (7.3 vs. 60.4 mg/dL; p = .018), increased day 14 weight (5.67 vs. 5.07 kg; p = .017) as well as a 13.7-fold decrease in serum conjugated bilirubin. Conclusion We demonstrate a novel relationship between the gut microbiota and systemic inflammation in a TPN animal model. Pertinently, the degree of gut dysbiosis correlated with the severity of systemic inflammation. This study underscores the role of gut microbiota in driving liver injury mechanisms during TPN and supports a paradigm change in therapeutic targeting of the gut microbiota to mitigate TPN-related injury. KEY MESSAGES This study identified a differential link between gut microbiota and inflammation—the higher the dysbiosis, the worse the systemic inflammatory markers. Higher levels of...