Acetaminophen-induced fulminant liver failure (clinical case presentation and a review of the literature)

Abstract

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.