Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial condition, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis. NAFLD affects both adults and children who present with particular risk factors, including obesity, sedentary lifestyle and/or a predisposing genetic background. The escalation of the prevalence of NAFLD in children worldwide is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. The etiopathogenesis of primary NAFLD in children is unknown; however, considerable knowledge about the mechanisms of liver damage that occur during disease progression has been gathered over the past 30 years. Understanding the pathogenetic mechanisms, together with the histological pattern, provide the basis to characterize potential early predictors of the disease, suitable noninvasive diagnostic tools and design novel specific treatments and possible management strategies. Despite a few clinical trials on the use of antioxidants combined with lifestyle intervention for NAFLD that showed encouraging results, to date, no treatment guidelines exist for children with NAFLD. In this Review, we provide an overview of current concepts in epidemiology, histological features, etiopathogenesis, diagnosis and treatment of NAFLD in children and adolescents.

Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents

“…The growing prevalence of childhood obesity and overweight in industrialized countries is leading to a parallel surge in the prevalence of pediatric non-alcoholic fatty liver disease (NAFLD) (Vajro et al 2012;Alisi et al 2012;Loomba et al 2009). Pediatric NAFLD is not always a benign condition, with some children progressing to steatohepatitis (NASH) and fibrosis, with possible evolution to cirrhosis and liver failure (Loomba et al 2009;Feldstein et al 2009;Nobili et al 2013).…”

“…NAFLD affects 3-13 % of children and adolescents, and this figure increases up to approximately 80 % among obese individuals (Feldstein et al 2009;Nobili et al 2013). These children are at lifetime risk of developing metabolic complications such as dyslipidemia, insulin resistance, hypertension, and type 2 diabetes, as well as other features of the metabolic syndrome (Vajro et al 2012;Alisi et al 2009Alisi et al , 2012Loomba et al 2009;Feldstein et al 2009;Nobili et al 2013). During adolescence, children start following a personalized lifestyle characterized by excessive caloric intake, and sedentary lifestyle.…”

Non-alcoholic fatty liver disease: a new epidemic in children

“…4 According to the World Health Organization (WHO), obesity is a multifactorial and complex chronic disease occurring when calories consumed exceed energy expenditure over a long enough period. It usually Obesity is the most common nutritional disorder in developed countries.…”

Lysosomes ‘in control’

“…OSEs are products of lipid peroxidation and include the expression of the highly immunogenic products MDA and acetaldehyde-adducted products (MAA), oxidized cardiolipin, phosphocholine (PC) and 4-hydroxynonenal (4-HNE). 86 As such, boosting an immune response specifically to the PC-epitope of oxLDL was shown to reduce atherosclerosis 87 and NASH 35 in vivo and was associated with less foamy macrophages. Therefore, an attractive way to prevent the aforementioned deleterious effects of oxLDL-derived oxidized lipids on liver cells is the increase of circulating antibodies specifically directed to oxLDL.…”

“…LDL-derived cholesteryl esters (CEs) are internalized by means of LDL receptor-mediated endocytosis, eventually reaching the lysosome where the action of lysosomal acid lipase (LAL) generates free unesterified cholesterol (FC) 86 ( Figure 1.5). Lysosomal efflux of this FC to the cytoplasm is regulated by the Niemann-Pick disease type C1 (NPC1) and NPC2 proteins.…”