Idiosyncratic drug-induced liver injury

Lammert, C., Einarsson, S., Saha, C Niklasson, A., Bjornsson, E. and Chalasani, N. (2008) Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury search for signals. Hepatology (Baltimore, Md), 47, 2003-2009. 

Lucena MI, Andrade RJ, Martinez C, et al. Glutathione S-transferase ml and tl null genotypes increase susceptibility to idiosyncratic drug-induced liver injury. Hepatology. 2008 48(2) 588-596. 

Amacher DE (2012) The primary role of hepatic metabolism in idiosyncratic drug-induced liver injury. Expert Opin Drug Metab Toxicol 8(3) 335-347... 

For reasons that are unclear, drug-induced liver injury affects females more than males Females accounted for approximately 79% of all reactions to acetaminophen and 73% of all idiosyncratic drug-induced reactions (88). Females exhibit increased risk of hepatic injury from drugs such as atorvastatin, nitrofurantoin, methyidopa, and diclofenac. 

UlzmTun, E., Stephens, C., Crespo, E., Ruiz-CabeUo, F., Ruiz-Nunez, J., Saenz-L6pez, R, Moreno-Herrera, I., Robles-Diaz, M., Hallal, H., Moreno-Planas, J.M., Maria, R., Cabello, M.R., Lucena, M.I., and Andrade, R.J. (2013) Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury. Liver Int., 33, 1378-1385. 

Idiosyncratic Toxicity While idiosyncratic drug-induced liver injury (IDILI) toxicity is a relatively rare occurrence, it may result in significant consequences for both the individuals involved and the future marketability of the compound that associated with the toxicity. Since idiosyncratic toxicides in general are typically rare events in a... 

Roth, R.A. and Ganey, P. (2011) Animal models of idiosyncratic drug-induced liver injury—current status. Crit. Rev. Toxicol. 41, 723-739. 

Hussaini, S. H. Farrington, E. A. 2014. Idiosyncratic drug-induced liver injury an update on the 2007 overview. Expert Opinion on Drug Safety, 13, 67-81. 

Laifenfeld, D., Qiu, L., Swiss, R., et al. 2013. Utilization of eausal reasoning of hepatic gene expression in rats to identify molecular pathways of idiosyncratic drug-induced liver injury. Toxicol. Sci. 137(1 ) 234-248. 

Kim SH, Naisbitt DJ (2016) Update on advances in research on idiosyncratic drug-induced liver injury. Allergy Asthma Immunol Res 8 3-11... 

The reaction is generally a type fV hypersensitivity response involving CD4+ cells, CD8+ cytotoxic lymphocytes and NK, Kupffer, and dendritic cells. Type II hypersensitivities may also sometimes occur. Knowledge of mechanisms underlying idiosyncratic drug-induced liver injury is limited. 

Critical Review Is There a Link between BSEP Inhibition, Drug-Induced Cholestasis and Idiosyncratic Liver Injury ... 

Aithal GP. Diclofenac-induced liver injury A paradigm of idiosyncratic drug toxicity. Expert Opin Drug Saf. 2004 3(6) 519-523. 

A number of experimental and clinical reports have suggested that a variety of factors unrelated to drug metabolism and direct hepatotoxicity may also influence susceptibility to DILL In addition, the nature of idiosyncratic liver injuries suggests that a majority of these reactions involve an immune mechanism. Hepatic cellular dysfunction and death have the ability to initiate immunological reactions, including both adaptive and innate immune responses. This inflammatory process has been implicated in the development of liver injury induced by such drugs as APAP, dihydralazine, and halothane (Laskin and Gardner 2003 Liu and Kaplowitz 2002 Luster et al. 2001). 

Kashimshetty, R., Desai, V.G., Kale, V.M., Lee, T., Moland, C.L., Branham, W.S., New, L.S.,Chan, E.C.,Younis, H., Boelsterh, U.A. (2009). Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicology and Applied Pharmacology, 238, 150-159. 

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