New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

Abstract

Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.