Halothane-induced liver injury

Bourdi M, Amouzadeh HR, Rushmore TH, Martin JL, Pohl LR (2001) Halothane-induced liver injury in outbred guinea pigs role of trifluoroacetylated protein adducts in animal susceptibility. Chem Res Toxicol 14 362-370... 

Yang J, Qiao FIL, Dong ZM (2005) Polymorphisms of IL-13 and IL-4-IL-13-SNPs inpatients with penicillin allergies. Eur J Clin Pharmacol 61 803-809 Yee SB, Bourdi M, Masson MJ, Pohl LR (2007) Hepatoprotective role of endogenous interleukin-13 in a murine model of acetaminophen-induced liver disease. Chem Res Toxicol 20 734—744 You Q, Cheng L, Reilly TP, Wegmann D, Ju C (2006) Role of neutrophils in a mouse model of halothane-induced liver injury. Hepatology 44 1421-1431... 

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). 

Hepatic damage related to isoflurane anesthesia has very occasionally been described (9,10), including one report of hepatic necrosis and death (11). Hepatitis or hepatocellular injury has been described with all current volatile anesthetics. Among these, halothane-associated hepatitis has been best characterized and is probably caused by an immune reaction induced by hepatocyte proteins that have been covalently trifluoroacetylated by the trifluoro-acetyl metabolite of halothane. The reactive acyl-halide metabolite of trifluoroacetic acid can trifluoroacetylate liver proteins, resulting in immune-mediated hepatic necrosis (12). However, isoflurane biotransformation to trifluoroacetate is less than 0.2%, compared with 15-20% for halothane. 

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