Understanding susceptibility and targeting treatment in non-alcoholic fatty liver disease in children; moving the fulcrum.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of paediatric liver disease, affecting 10% of school-aged children and 44-70% of obese children and young people (CYP) in the western world. Encompassing a spectrum from simple steatosis to steatohepatitis and progressive fibrosis, the disease is rapidly becoming the most common indication for liver transplantation. The molecular pathogenesis of NAFLD remains only partially understood. Development and progression of NAFLD is influenced by genetic and nutritional factors, insulin resistance, oxidative stress, gut microbiome, bile acid metabolism and lipid/glucose handling and is closely associated with overweight and obesity. Lifestyle change is the only proven effective treatment for paediatric NAFLD, however this is difficult to achieve in many. Given that moderate or severe fibrosis is already present in 30-50% of children with NAFLD at the time of presentation, progression in CYP may be more rapid, though adequate outcome data do not yet exist in this cohort. CYP with NAFLD are an excellent population in which to study underlying mechanisms and interventions to correct disease progression as they are largely unaffected by other environmental influences such as alcohol and may represent the more severe end of the spectrum in terms of early onset. Undoubtedly genetic and epigenetic mechanisms determine a large proportion of susceptibility to the disease and potentially, identification of individuals at risk may allow for targeted therapy. This review with give a clinical perspective of paediatric NAFLD focused on identifying those at risk of progressive disease and what to consider in attempting to modify risk.