Unmet needs in pediatric NAFLD research: what do we need to prioritize for the future?

Introduction: Pediatric nonalcoholic fatty liver disease (NAFLD) is common disorder that has complex pathophysiology and unquantified clinical significance. Though there have been major advances in the field, there is much yet to be understood. Areas covered: PubMed/MEDLINE and Embase were searched for articles related to pediatric NAFLD and nonalcoholic steatohepatitis (NASH) between January 1998 and January 2018. The areas considered to be ‘unmet needs’ were the relationship between the intestinal microbiome and perinatal events, clinical event risk stratification, and mechanisms underlying portal inflammation. Expert commentary: In utero and ex utero factors have been associated with NAFLD and also with the intestinal microbiome, but it is not yet known how intestinal dysbiosis can be reversed and whether intervention in high-risk neonates could alter their propensity for the metabolic syndrome. Children with NAFLD are at increased risk of cardiovascular, diabetic, and hepatic diseases, but it is unclear how best to stratify children into appropriate risk groups for targeted interventions. Finally, the immune processes underlying pediatric NASH are thought to differ to those in adult NASH, yet the events surrounding activation of periportal lymphocytes are poorly understood. Deepening our understanding of these topics may lead to novel therapeutic targets.