Fatty Liver Disease in Obese Children

Physical activity (PA)-induced weight reduction, the suggested therapy for noalcoholic liver disease (NAFLD), is difficult and its maintenance is typically unsuccessful in children, affirming the acute need for alternative/adjunct therapies. Although few promising approaches have been reported, the benefits are incongruent and mostly marginal. N-acetyl cysteine (NAC), a derivative of the natural amino acid, cysteine, appears to be promising as an adjunct therapy to PA. Animal and a few adult human studies suggest NAC-induced attenuation of liver abnormalities, oxidative stress, insulin resistance and inflammation. The primary aim of the proposal is to determine in obese children with biopsy proven NASH and elevated liver enzymes the effect of NAC at two different doses on liver fat using magnetic resonance imaging (MRI), liver enzymes and risk factors of cardiometabolic disease. We hypothesize that NAC will produce beneficial effect on these parameters.

Inclusion criteria

• Age 7 years and older
• NASH confirmed in a previous biopsy
• HbAIc <6.4%
• ALT > 60 U/L or 1.5 times the upper limit of normal

Exclusion criteria

• Chronic liver disease including alpha-1-antitrypsin deficiency, Wilson's disease, autoimmune and viral hepatitis
• Medications such as adrenergic β-blockers, steroids and other drugs known to interfere with the measurement of liver enzymes and risk factors for cardiovascular disease
• Heart disease, chronic renal disease, adrenal, hepatic or thyroid dysfunction; active malignancy; and anemia
• History of prior treatment with NAC
• Evidence of hypersensitivity/allergy to NAC
• Alcoholism or drug abuse and smoking
• Inter-current illness over 7 days before the study & surgery in the past 3 mo.