Advances in Pediatric Nonalcoholic Fatty Liver Disease†

Abstract

Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two-to three-fold rise in the rates of obesity and overweight in children over the last two decades is probably responsible for the NAFLD epidemic. Emerging data suggest that children with nonalcoholic steatohepatitis (NASH) progress to cirrhosis, which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents are associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Noninvasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD. Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community. (HEPATOLOGY 2009;50:1282-1293

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…Considerations include inborn errors of fatty acid or carnitine metabolism, peroxisomal disorders, lysosomal storage disorders, Wilson's disease, and cystic fibrosis. 189 However, as in adults, positive serum autoantibodies are present in a significant population of children with biopsy-proven NAFLD and on some occasion liver biopsy is required to discriminate between autoimmune hepatitis and NAFLD. 63 Obviously, the confounding factor of alcoholism is much less common in children and standard questionnaires for quantifying alcohol intake are usually unnecessary.…”

“…Open-label proof-of-concept studies have utilized changes in serum ALT or liver brightness on ultrasound as endpoints. 189 Agents evaluated thus far include metformin, vitamin E, ursodeoxycholic acid and delayed-release cysteamine. 189 Recently, a large multicenter RCT using change in histology as a secondary endpoint was published.…”

“…189 Agents evaluated thus far include metformin, vitamin E, ursodeoxycholic acid and delayed-release cysteamine. 189 Recently, a large multicenter RCT using change in histology as a secondary endpoint was published. 130 This study, called TONIC, compared the efficacy of vitamin E or metformin to placebo in 8-17 year olds with NAFLD.…”

Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents

“…The growing prevalence of childhood obesity and overweight in industrialized countries is leading to a parallel surge in the prevalence of pediatric non-alcoholic fatty liver disease (NAFLD) (Vajro et al 2012;Alisi et al 2012;Loomba et al 2009). Pediatric NAFLD is not always a benign condition, with some children progressing to steatohepatitis (NASH) and fibrosis, with possible evolution to cirrhosis and liver failure (Loomba et al 2009;Feldstein et al 2009;Nobili et al 2013). NAFLD affects 3-13 % of children and adolescents, and this figure increases up to approximately 80 % among obese individuals (Feldstein et al 2009;Nobili et al 2013).…”

“…NAFLD affects 3-13 % of children and adolescents, and this figure increases up to approximately 80 % among obese individuals (Feldstein et al 2009;Nobili et al 2013). These children are at lifetime risk of developing metabolic complications such as dyslipidemia, insulin resistance, hypertension, and type 2 diabetes, as well as other features of the metabolic syndrome (Vajro et al 2012;Alisi et al 2009Alisi et al , 2012Loomba et al 2009;Feldstein et al 2009;Nobili et al 2013). During adolescence, children start following a personalized lifestyle characterized by excessive caloric intake, and sedentary lifestyle.…”