Unexplained hepatitis following halothane.

Abstract

SummaryFull clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95°o of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 551)O of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted.Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-

Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug.

“…A trifluoroacetyl chloride adduct, which could be the trifluoroacetylated cytochrome P-450, appeared on the rat hepatocyte membrane (19). Moreover, evidence was provided that sera from several patients recovering from severe hepatitis after halothane treatment contained specific anti-organelle autoantibodies, called anti-LKM1 in that case (1,4,20). These antibodies were found to interact specifically with hepatocytes from halothane-treated rabbits and to activate their destruction by lymphocytes (4).…”

Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

“…Firstly, obese patients could be more prone to develop drug-induced acute hepatitis. This has been suggested for the volatile halogenated anaesthetic halothane [287][288][289], APAP [290,291], and different drugs, such as losartan, ticlopidine, and omeprazole [292]. Interestingly, it has been reported that diabetes also increases the risk of acute liver failure (ALF), including drug-induced ALF [293].…”

Idiosyncratic Drug Reactions

“…However, these factors appear to be associated with specific IDRs [16]. Although women appear to be at increased risk for IDRs caused by some drugs (e.g., halothaneinduced hepatitis) and for idiopathic autoimmune reactions (e.g., lupus and autoimmune thyroid disease), other autoimmune diseases, such as type 1 diabetes, do not have such a female predominance [16,56]. Similarly, while the risk of drug-induced liver toxicity (e.g., isoniazid and acetaminophen) increases with age, the risk of valproic acid liver toxicity is greater in children than adults [16].…”

“…Similarly, while the risk of drug-induced liver toxicity (e.g., isoniazid and acetaminophen) increases with age, the risk of valproic acid liver toxicity is greater in children than adults [16]. Halothane-induced hepatotoxicity occurs more commonly in obese patients, which is attributed to the distribution of halothane to fat, thereby requiring higher doses of drug to achieve effect [56]. Although it is generally believed that preexisting liver disease does not increase susceptibility to hepatic IDRs, there appears to be exceptions to this dogma [16,57].…”