Although drug-induced liver injury (DILI) has a rare occurrence, it is potentially a life threatening adverse drug reaction. The morphologic characteristic of DILI are similar to acute or chronic liver disease while its histopathologic features may be identical to those of other causes of liver injury, such as acute viral hepatitis.

Various factors are related to increased susceptibility to DILI. Among these, genetic susceptibility is an important factor. Various studies have highlighted on the role of single nucleotide polymorphisms (SNP) within transporter genes. A small study series also found the association between polymorphisms in CYP2C9 and CYP2C19 and DILI. Contrary to this, a large study on DILI patients showed that polymorphisms in these isoforms were not correlated with increased susceptibility to DILI, and, genetic variation in CYP2C9 and CYP2C19 may not be considered a DILI risk factor. Besides, CYP2D6, another gene with allelic variants and encoding enzymes with variable degrees of activity, is correlated with the development of hepatotoxicity after administration of drugs, including antidepressants and herbal products. In addition, CYP2E1 genotype has been found to be associated with increased susceptibility to DILI, particularly in patients undergoing antituberculosis therapy. 

Another risk factor is the adaptive immune system, which is implicated mechanistically in idiosyncratic DILI. The hypothesis suggests that either the drug metabolite or parent drug binds to hepatic proteins to form a neoantigen and activates the immune system to produce antibodies against the hepatic proteins. This mechanism can be seen in diclofenac-induced liver injury. Moreover, autoantibodies against the CYP450 enzymes were seen in cases of DILI including ingestion of halothane, tienilic acid, dihydralazine, and anticonvulsant drugs.

Another factor associated with the susceptibility of DILI is drug-drug interaction and hepatic metabolism, the risk of idiosyncratic DILI is usually amplified with higher doses of a medication and a dose of more than 50 mg daily, particularly if the drug exhibits extensive hepatic metabolism. This increased risk is ascribed to the production of reactive intermediaries and successive metabolic idiosyncrasy. 

Besides, underlying disease is a crucial risk factor in the development of both intrinsic and idiosyncratic DILI. Abnormal liver function in the liver disease changes the expression of drug transporter proteins in the liver and other organs as well. Additionally, underlying liver disease can alter the pharmacokinetics of drugs and can lead to severe consequences. 

Source: Khoury T, Rmeileh AA, Yosha L, Benson AA, Daher S, Mizrahi M. Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options. J Clin Transl Hepatol. 2015;3(2):99-108.