The most common non-infectious causes of hepatitis are alcohol, cholestatic, drugs and toxic materials, apart from infectious or viral hepatitis. The most common mode causing liver injuries is antituberculosis drug-induced hepatitis. The severity of drug-induced liver injury has a spectrum of variation ranging from minor nonspecific changes in hepatic structure to fulminant hepatic failure, cirrhosis and liver cancer. Moreover, it has been observed that patients receiving antitubercular drug commonly develop acute or chronic hepatitis. 

Evidences suggest that the time needed for the metabolites to reach hepatotoxic levels is much earlier with isoniazid plus rifampicin treatment in comparison to isoniazid alone. Antituberculosis drug (ATT)-inducible cytochrome P-4502E1 (CYP2E1) is constitutively expressed in the liver. Furthermore, polymorphism of the N-acetyltransferase 2 (NAT2) genes and glutathione-S-transferase (GST) are regarded as the major susceptibility risk factors for ATT-induced hepatitis. The hepatic NAT and GST are implicated in the metabolism of several carcinogenic arylamines and drugs. The NAT2 enzyme has a genetic polymorphism in human and have been found to be causative factor for genetic polymorphism of slow and rapid acetylation in humans. Additionally, slow acetylators of NAT2 has shown evidence of developing more severe hepatotoxicity in contrast to rapid acetylators, indicative of a significant risk factor. Moreover, homozygous null mutations at GSTM1 and GSTT1 loci leading to the deficiency of GST activity have the potential to modulate susceptibility to drug and xenobiotic-induced hepatotoxicity. Researchers have also demonstrated that polymorphisms at GSTM1, GSTT1 and NAT2 loci were associated with various forms of liver injury, including hepatocellular carcinoma.

Source: Hussain Z, Kar P, Husain SA. Antituberculosis drug-induced hepatitis: risk factors, prevention and management. Indian J Exp Biol. 2003 Nov;41(11):1226-32. PMID: 15332488.