Results: Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P = .26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P = .83). The mean change in ALT level from baseline to 96 weeks was -35.2 U/L (95% CI, -56.9 to -13.5) with placebo vs -48.3 U/L (95% CI, -66.8 to -29.8) with vitamin E (P = .07) and -41.7 U/L (95% CI, -62.9 to -20.5) with
metformin (P = .40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, -0.2 to 0.3) vs -0.5 with vitamin IWR-1 order E (95% CI, -0.8 to -0.3; P = .006) and -0.3 with metformin (95% CI, -0.6 to -0.0; P = .04); and in NAFLD activity score, -0.7 with placebo (95% CI, -1.3 to -0.2) vs -1.8 with vitamin E (95% CI, -2.4 to -1.2; P = .02) and -1.1 with metformin (95% CI, -1.7 to -0.5; P = .25). Among children with NASH, the proportion who resolved at 96 weeks was 28% with placebo (95% CI, 15% to 45%; 11/39) vs 58% with vitamin E (95% CI, 42% to 73%; 25/43; P = .006) and 41% with metformin (95% CI,
26% to 58%; 16/39; P = .23). Compared with placebo, neither therapy demonstrated significant improvements in other histological features. Conclusion: Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD. TRIAL REGISTRATION: clinicaltrials.gov FK228 research buy Identifier: NCT00063635. Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children1 and is a major reason for referral to pediatric gastroenterologists and hepatologists. This dramatic increase in the prevalence of NAFLD is a direct consequence of the childhood obesity epidemic, with an estimated 10% of U.S. children having fatty liver.2 The spectrum
of NAFLD ranges from the benign form of hepatic steatosis, with the accumulation of lipids in the liver, to the progressive form of nonalcoholic steatohepatitis (NASH), which find more is characterized by steatosis along with inflammation, hepatocyte injury, and variable degrees of fibrosis.3 It is important to recognize that NASH may present with a distinct histological pattern in children, mainly characterized by increased portal inflammation and fibrosis, as opposed to the predominantly lobular inflammation and perisinusoidal fibrosis observed in adults.4, 5 The progression of NASH to cirrhosis that requires liver transplantation during childhood is well documented,6 making the identification of effective therapy for this condition a pressing issue. Weight loss may improve the liver disease or even lead to the resolution of NAFLD in some children,7 but other than lifestyle advice on diet and exercise, there are no approved therapies for pediatric NAFLD. Insulin resistance (IR) and oxidative stress (OS) play a significant role in disease development and progression (Fig.