Effect of N-acetyl Cysteine in Children With Nonalcoholic Steatohepatitis

Background: Oxidative stress and inflammation play crucial roles in the progression of benign nonalcoholic fatty liver disease (NAFLD) to its severe form, nonalcoholic steatohepatitis (NASH) with its sequelae of liver scarring, cirrhosis and cancer. Given the lack of successful and sustainable intervention approaches, there is a strong demand for new and/or adjuvant therapies. We determined the effect of N-acetyl cysteine (NAC), a precursor of de novo glutathione (GSH) synthesis and with potent antioxidant and anti-inflammatory properties, in children with biopsy-proven NASH. Methods: In a randomized, double-blind, placebo-controlled trial of NAC in children (age: 8-18 years old) with biopsy-proven NASH (NAS Score >2) the participants (n=13) were randomized to one of the three groups of NAC treatment for 16-weeks: Group 1 (600 mg NAC/day); NAC group 2 (1200 mg NAC/day); and Group 3 (Placebo). Erythrocyte GSH was measured along with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and biomarkers of inflammation such as high-sensitivity c-reactive protein (hs-CRP) and interleukin-6 (IL-6). Liver fat fraction (LFF) was measured using magnetic resonance imaging (MRI). For data analysis, the 600 mg and 1200 mg NAC groups were collapsed into one group, the 'intervention group'. Results: NAC for 16 weeks enhanced erythrocyte GSH concentration and decreased circulating plasma AST (58.13±9.51 to 39.5±10.1 IU/L; p=0.002), ALT (89.56±30.43 to 68.56±26.50 IU/L; p