Nonalcoholic fatty liver disease

Lindor et al. provide an excellent and up-to-date review of nonalcoholic fatty liver disease (NAFLD) in adults but they do not discuss NAFLD in children (1). Childhood NAFLD has been reported globally since our first large clinical series from the Hospital for Sick Children in Toronto was published (2). In part this reflects the increasing prevalence of obesity in childhood (3,4). NAFLD is typically diagnosed in children 12 -14 years-old, but serious liver disease associated with NAFLD has been reported in children as young as five years of age (5,6). In adults NAFLD must be differentiated from alcoholic liver disease, but in children NAFLD must be distinguished from various rare metabolic disorders which cause fatty liver (such as Wilson disease). The typical child suffers from over- nutrition, is asymptomatic or has vague abdominal pain and may have abnormal liver biochemistries. As in adults, an important feature of childhood NAFLD is hyperinsulinemia associated with relative insulin resistance, as shown by clinical studies using the homeostasis model of insulin resistance (HOMA-IR) (5). Whether oxidative damage to the liver is prominent in childhood NAFLD is a question currently being investigated. NAFLD in adults can progress to cirrhosis with chronic liver failure requiring liver transplantation or to hepatocellular carcinoma, but the long-term outcome for children with NAFLD is unknown. Cirrhosis has been reported in a few children (6). Although simple steatosis (hepatic fat accumulation without inflammation and fibrosis) carries a benign prognosis in adults, the long-term outcome for children with simple steatosis is uncertain. Current treatment strategies in NAFLD are aimed at eliminating or reducing risk factors associated with NAFLD: they involve weight loss and increased physical activity. In children few data are available regarding pharmacological interventions such as vitamin E, ursodiol and metformin (7-9). Well-designed prospective studies in children are urgently needed to determine the best overall medical management. Childhood NAFLD may be the hepatic manifestation of the metabolic dysregulation leading to type 2 diabetes, hypertension and cardiovascular disease. Given that childhood NAFLD is highly prevalent—estimated at 3-10% of obese children—we need to intervene now so as to avoid cirrhosis, as well as these diseases, in the current generation of children.

Diana Mager, PhD RD Eve Roberts, MD FRCPC Division of Gastroenterology, Hepatology and Nutrition, and Metabolism Research Program, The Hospital for Sick Children, Departments of Paediatrics, Medicine and Pharmacology, University of Toronto.

References. 1. Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ 2005; 172: 899-905. 2. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000; 30: 48-53. 3. Canning PM, courage ML, Frizzell LM. Prevalence of overweight and obesity in a provincial population of Canadian preschool children. CMAJ 2004: 171: 240-242. 4. Janssen I, Katzmarzyk PT, Boyce WF, Vereecken C, Mulvihill C, Roberts C, Currie C, Pickett W and the Health Behavior in School-aged Children Obesity Working Group. Comparison of overweight and obesity prevalence in school-aged youth from 34 countries and their relationships with physical activity and dietary patterns. Obesity Reviews 2005; 6: 123-132. 5. Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE. Obesity, insulin resistance and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 2003; 143: 500-505. 6. Roberts EA. Non-alcoholic fatty liver disease (NAFLD) in children. Front Biosci 2005; 10: 2306-2318 (in press). 7. Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000; 136: 734-738. 8. Vajro P, Franzese A, Valerio G, Iannucci MP & Aragione N. Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children. J Pediatr 2000; 136: 739-743. 9. Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non- alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 31: 871-879.

Conflict of Interest:

None declared