Endocrine Abstracts

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease in children and adolescents in the United States, disproportionately affecting certain ethnic and racial groups. A 2 to 3-fold rise in the prevalence of obesity and overweight in children over the last 3 decades highly relates to the NAFLD epidemic. There are concerns that children with nonalcoholic steatohepatitis (NASH) are more prone to progress to cirrhosis, which may increase liver-related mortality in adulthood. Also worrisome is the recognition that cardiovascular risk and type 2 diabetes in children and adolescents are associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that recognized in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Further pediatric-specific noninvasive biomarker development is needed to diagnose and monitor those with NASH. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed, as unique regulatory considerations impede pediatric therapeutic trials with agents demonstrating current promise in adults. Randomized-controlled trials in children and adolescents to date show improvement in particular histologic aspects of NASH, for which vitamin E appears effective. Public health awareness and lifestyle interventions are needed to promote healthy diets, exercise, and lifestyle modifications to prevent and reduce the burden of disease. BULLET POINTS:- - Fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in pediatric populations in developed nations.- Certain ethnic groups such as indigenous Mexican-Americans, South Pacific Islanders, and Middle Easterners are more prone, and male gender, obesity and insulin resistance are most frequent concomitants- The unique histologic pattern of earlier-onset NAFLD in children demonstrates a pattern of periportal steatosis and fibrosis, with relative lack of hepatocellular ballooning, in contrast to the later onset and adult pattern with panacinar steatosis, ballooning cell injury, and perivenular fibrosis.- Limited randomized clinical controlled trials in pediatrics utilizing liver histology demonstrate utility and safety of vitamin E to improve NASH histology, while no agents have yet been proven in pediatrics to improve fibrosis.- In order to mitigate this problem, better noninvasive tests validated in pediatric cohorts need attention, and extrapolated efficacy of drugs shown effective in adult trials need to be shown to be safe before widespread use. Until then, prevention and treatment needs to be aimed at identifying those at risk and promoting healthy lifestyle interventions.