Paediatric fatty liver disease (PeFLD): All is not NAFLD – Pathophysiological insights and approach to management

Abstract

The recognition of a pattern of steatotic liver injury where histology mimicked alcoholic liver disease, but alcohol consumption was denied, led to the identification of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease has since become the most common chronic liver disease in adults owing to the global epidemic of obesity. However, in paediatrics, the term NAFLD seems incongruous: alcohol consumption is largely not a factor and inherited metabolic disorders can mimic or co-exist with a diagnosis of NAFLD. The term paediatric fatty liver disease may be more appropriate. In this article, we summarise the known causes of steatosis in children according to their typical, clinical presentation: i) acute liver failure; ii) neonatal or infantile jaundice; iii) hepatomegaly, splenomegaly or hepatosplenomegaly; iv) developmental delay/psychomotor retardation and perhaps most commonly; v) the asymptomatic child with incidental discovery of abnormal liver enzymes. We offer this model as a means to provide pathophysiological insights and an approach to management of the ever more complex subject of fatty liver.

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

“…Whatever its etiology, microvesicular steatosis is thought to be deleterious for the liver, in particular as the consequence of mitochondrial dysfunction and energy shortage [70][71][72].…”

A mouse model for spinal muscular atrophy provides insights into non-alcoholic fatty liver disease pathogenesis

“…Microvesicular steatosis is present in all Smn 2B/mice. In the pediatric population, microvesicular steatosis is generally clinically associated with inherited metabolic disorders and fatty acid oxidation defects [42]. In contrast, it is only present in a minority (10%) of adult NAFLD patients and associated with more severe disease [43].…”

When a secondary form of pediatric non-alcoholic fatty liver disease should be suspected?

“…Obesity is the most important risk factor for NAFLD [2,10,11]. This condition, in fact, is closely related to central obesity with insulin resistance and additional factors (e.g.…”

“…As in adulthood, NAFLD in childhood is associated with an increased cardiometabolic risk. Given that, all NAFLD patients should be assessed for cardiovascular risk [2,10].…”

“…autoimmune hepatitis, genetic, congenital conditions) [2]. Besides primary NAFLDclosely related to visceral obesity and insulin-resistance and highly associated with metabolic impairments-, there are various secondary forms of NAFLD (due to systemic, congenital or metabolic causes) requiring high attention by pediatricians because of in some case a correct diagnosis might be lifesaving [3][4][5][6][7][8][9][10][11]. In fact, these forms might reveal several important liver diseases needing a major effort in early identification, management andif possibletreatment.…”