Effects of Docosahexaenoic Acid (DHA) on Children With Nonalcoholic Fatty Liver Disease (NAFLD) (EDACN)

Study of Efficacy and Tolerability of Docosahexaenoic Acid (DHA) on Children Affected by Nonalcoholic Fatty Liver Disease (NAFLD).

The purpose of this interventional study is to evaluate the efficacy and tolerability of docosahexaenoic acid (DHA) in children or adolescents with well-characterized and liver biopsy confirmed nonalcoholic fatty liver disease (NAFLD).

Sixty children or adolescents (4-16 years) with liver biopsy proven NAFLD will be enrolled. They will be randomized to treatment with DHA 250 mg/kg/d (n=20), DHA 500 mg/kg/d (n=20), or an identical placebo (n=20) given orally for a period of 24 months. All patients will be included in a lifestyle intervention program consisting of a diet tailored on the individual requirements and physical exercise. Patients will undergo a medical evaluation every three months during the 24-month study period. Liver biopsy will be performed only at baseline and at the end of treatment. Anthropometric analysis, laboratory tests, including liver enzymes and lipids will be repeated at 3-month intervals during the 24-month study duration. Ultrasonography and Fibroscan of the liver will be repeated at the end of the study period.

DHA 250 mg/kg/d plus lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].

DHA 250 mg/kg/d plus lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].

placebo and lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity].

lifestyle intervention [including hypocaloric diet (25-30 cal/kg/d) or isocaloric diet (40-45 cal/kg/d) and physical activity], for 12 months.

Inclusion Criteria: persistently elevated serum aminotransferase levels diffusely echogenic liver on imaging studies suggestive of fatty liver biopsy consistent with the diagnosis of NAFLD Exclusion Criteria: hepatic virus infections (HCV RNA-PCR negative) Hepatitis A, B, C, D, E and G cytomegalovirus and Epstein-Barr virus alcohol consumption history of parenteral nutrition use of drugs known to induce steatosis or to affect body weight and carbohydrate metabolism autoimmune liver disease, metabolic liver disease, Wilson's disease, and a-1-antitrypsin-associated liver disease were ruled out using standard clinical, laboratory and histological criteria

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Nobili V, Alisi A, Della Corte C, Rise P, Galli C, Agostoni C, Bedogni G. Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children. Nutr Metab Cardiovasc Dis. 2013 Nov;23(11):1066-70. doi: 10.1016/j.numecd.2012.10.010. Epub 2012 Dec 7.

Nobili V, Bedogni G, Alisi A, Pietrobattista A, Rise P, Galli C, Agostoni C. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child. 2011 Apr;96(4):350-3. doi: 10.1136/adc.2010.192401. Epub 2011 Jan 12.