Alcohol, cholestatic, drugs and toxic materials are other most common non-infectious causes of hepatitis apart from infectious or viral hepatitis. The utmost common approach that leads to liver injuries is antituberculosis drug-induced hepatitis. The sternness of drug-induced liver injury varies from slight nonspecific changes in hepatic structure to fulminant hepatic failure, cirrhosis and liver cancer. Patients receiving antitubercular drug regularly develop acute or chronic hepatitis. The period required for the metabolites to reach hepatotoxic levels is much earlier with isoniazid plus rifampicin treatment as compared to isoniazid alone and this has been shown to be synergistic rather than additive. Antituberculosis drug (ATT)-inducible cytochrome P-4502E1 (CYP2E1) is constitutively articulated in the liver. Latest studies show that polymorphism of the N-acetyltransferase 2 (NAT2) genes and glutathione-S-transferase (GST) are the main susceptibility risk factors for ATT-induced hepatitis. The hepatic NAT and GST are involved in the absorption of some carcinogenic arylamines and drugs. The NAT2 enzyme has a inherited polymorphism in human. N-acetyltransferase 2 genes (NAT2) have been recognised to be responsible for genetic polymorphism of slow and rapid acetylation in humans. Slow acetylators of NAT2 prove to develop more severe hepatotoxicity than rapid acetylators making it a noteworthy risk factor. Insufficiency of GST activity, because of homozygous null mutations at GSTM1 and GSTT1 loci, may curb susceptibility to drug and xenobiotic-induced hepatotoxicity. Polymorphisms at GSTM1, GSTT1 and NAT2 loci had been associated to various forms of liver injury, together with hepatocellular carcinoma.

Source: Indian J Exp Biol, 2003 Nov;41(11):1226-32