Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide among children and adolescents. It encompasses a spectrum of disease, from its mildest form of isolated steatosis, to nonalcoholic steatohepatitis (NASH) to liver fibrosis and cirrhosis, or end-stage liver disease. The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes. Currently, liver biopsy is the gold standard for diagnosing NAFLD. However, given its invasive nature, there has been significant interest in developing noninvasive methods that can be used as accurate alternatives. Here, we review noninvasive biomarkers in pediatric NAFLD, focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic, sensitivity, and specificity. We examine two major approaches to noninvasive biomarkers in children with NAFLD. First, the biological approach that quantifies serological biomarkers. This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers. The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD. Each of these approaches was applied to children with NAFLD, NASH, and NAFLD with fibrosis. Finally, we suggest possible areas for future research based on current gaps in knowledge.