Causes of Acute Liver Failure:

Chronic infection with hepatitis C virus (HCV) is known to cause acute liver failure.

Alcohol-induced liver disease: 

Drug Induced Liver Disease (DILI): accounts for about 13% of cute liver failure in the US and is the 3rd most common cause of acute liver failure.

Mechanisms of Action

Developement of autoantibodies: 

–Cytochrome P450 2E1 (CYP2E1) is a 493 amino acid enzyme involved in the monooxygenation of drugs and other xenobiotic agents. It has been reported that autoantibodies to CYP2E1 eptiopes contributes to the development of hepatic autoimmune diseases. For example, autoantibodies to CYP2E1 have been identified in persons with drug induced liver injury (DILI). A type of DILI developed develops in susceptible individuals following adminsitration of halogenated volatile anesthetics. Oxidative metabolism of the anesthetic produces trifluoroacetylchloride (TFA) which is a reactive metabolite that can covalently bind to and alter native liver proteins. The TFA-protein complexes, known as drug haptens, are novel autoantigens or hapten autoantigen complexes (neoantigens) capable of eliciting allergic or autoimmune resposnes. A second type of DILI is alcohol induced liver diseases where individuals chronically exposed to alcohol also develop autoantibodies to CYP2E1. Chronic viral infections are also known to induce autoimmunity directed to CYP2E1. For example, chronic infection with HCV is known to induce autoimmune reacions. Individuals with chronic HCV expressed decreased levels of CYP2E1 as well as CYP2E1 autoantibodies. (Njoku (13/203402) discloses a CYP2E1 Gly113-Leu133 epitope that contributes to the development of hepatic autoimmune diseases. T and B cells specific for the Gly113-Leu133 epitope mediate an autoimmune response that contributes to the devleopment of hepatic autoimmune diseases. Methods for using the polypeptide for identifying a mammalain subject at resik of developing hepatic autoimmune disease are also provided. 

Susceptible individuals who develop anesthetic-induced DILI have elevated levels of CYP2E1 specific IgG4 autoantibodies. In constrast, exposed susceptible individuals who develop CYP2E1 specific IgG1 autoantibodies remain healthy. Accordingly, pathogenesis in hepatic autoimmune disease is assocaited with emergence of IgG4 autoantibodies and IgG4 autoanitbodies that are specific for the Gly113-Leu133 epitope of CYP2E1 can be used for diagnosing a pateint with hepatic autoimmune diasease.