Is it Simvastatin harmful in children? A case report

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children living in Western countries. Hyperlipidemia, obesity and insulin resistance are common components of the metabolic syndrome, which is frequently associated with NAFLD. Since patients with NAFLD are at high risk to develop cardiovascular disease (CVD), statins are frequently prescribed to patients with NAFLD and hyperlipidemia. The 3-Hydroxy-3-methyl-coenzyme A reductase (HMG-CoA reductase) is the rate limiting enzyme in cholesterol biosynthesis. Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding ?-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Under treatment with simvastatin, an improvement of enzymatic antioxidant parameters has been described in subjects with hypercholesterolemia. The safety and effectivity of statins in pediatric patients with NAFLD or non-alcoholic steatohepatitis (NASH), and their effect on hepatic fat infiltration or the extent of hepatic fibrosis are not known. Also, no evidences of the effects of a non therapeutic ingestion of this drug on the glutathione homeostasis and in children have been reported. We describe the case of a obese 4-year-old girl in whom an accidental overdose of simvastatin led to decrease levels of glutathione in blood with increase of the GSSG/GSH ratio. No adverse reactions were registered. All laboratory test were normal during the follow up. Only a 35% decrease of Glutathione was observed such as a possible mechanism of mithocondrial toxicity and depletion of the glutathione pool after the intake of excessive dose of HMG-CoA reductase inhibitors. Further RCTs are needed in order to establish the safety and efficacy to use of statin for pediatric NAFLD or NASH.