No proven treatment exists for nonalcoholic fatty liver disease (NAFLD) in children and adolescents. We sought to determine the efficacy of lifestyle intervention with or without antioxidant therapy in pediatric NAFLD. A total of 53 patients (age 5.7-18.8 years, 37 boys) were included. Lifestyle intervention consisting of a diet tailored to the patient's calorie needs, and increased physical activity was prescribed in all. Patients were concomitantly randomized to alpha-tocopherol 600 IU/day plus ascorbic acid 500 mg/day (n ‫؍‬ 25) or placebo (n ‫؍‬ 28), and treated for 24 months. The study was an extension of a previous study aimed at evaluating the effect of 12-month lifestyle intervention and antioxidant therapy on serum levels of aminotransferases. The primary end point of the present study was change in liver histology on repeated biopsy at 24 months. Secondary end points were changes in body weight, liver enzymes, and insulin sensitivity indices on 2-hour oral glucose tolerance test. The amount of weight lost at 24 months was similar in the placebo and antioxidant groups (؊4.75 [range, ؊16-4.0] versus ؊5.5 [range, ؊12.2-0.4] kg, respectively, P ‫؍‬ 0.9). A significant improvement occurred in the grade of steatosis, lobular inflammation, and hepatocyte ballooning, and in the NAFLD activity score in both groups. Levels of aminotransferases, triglycerides, cholesterol, fasting glucose, and insulin, and insulin sensitivity indices improved significantly as well. The improvement in all these parameters was not significantly different between the two groups. Conclusion: Lifestyle intervention with diet and increased physical activity induces weight loss and is associated with a significant improvement in liver histology and laboratory abnormalities in pediatric NAFLD. Alpha-tocopherol plus ascorbic acid does not seem to increase the efficacy of lifestyle intervention alone. (HEPATOLOGY 2008; 48:119-128.)

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Objective: Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3-18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology. Research methods and procedures: MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-b cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity. Results: MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (Pp0.05). Prevalence of a grade of steatosis X2 (P ¼ 0.05) and fibrosis (Pp0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis X2 with BMI z-score (P ¼ 0.04), fasting insulin (P ¼ 0.02), HOMA-IR (P ¼ 0.03), b-cell secretion (P ¼ 0.04); necroinflammation with BMI z-score (P ¼ 0.007), glucose (Pp0.0001), cholesterol (Pp0.04) and white blood cells (P ¼ 0.025); fibrosis with body weight (P ¼ 0.05), BMI z-score (P ¼ 0.03), cholesterol (P ¼ 0.05), triglycerides (P ¼ 0.05), fasting insulin (Pp0.0001) and mean values of the hormone at the OGTT (P ¼ 0.03), HOMA-IR (Pp0.0001)). Conclusion: Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.

Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy.