Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis.

Circulating antibodies reacting specifically with the cell membrane of hepatocytes isolated from halothane-anesthetized rabbits were detected in nine of 11 patients with fulminant hepatic failure after halothane-induced anesthesia. The immunoglobulin deposition, as revealed by immunofluorescence, showed a granular pattern on the hepatocyte surface membrane. Preincubation of halothane-pretreated, but not of control, hepatocytes with serum containing this antibody rendered them susceptible to cytotoxic effects of normal lymphocytes in vitro. Control studies using serum from subjects repeatedly exposed to halothane without the development of liver damage, and from patients with viral and toxic liver injury have confirmed the specificity of these findings to severe halothane-associated liver injury. These results provide further evidence of an immunologic component in this condition. (N Engl J Med. 1980; 303:66–71.) THE mechanisms responsible for the severe hepatic necrosis that occasionally follows halothane anesthesia are unknown. Current hypotheses suggest that a toxic reactive intermediary metabolite1 or a cell-damaging immune response2,3 is the basis for the tissue injury. Metabolic studies in animals and human subjects have provided evidence consistent with both reductive and oxidative pathways of degradation of halothane as the source of intermediate products that bind to intracellular constituents and may disrupt the metabolic integrity of the hepatocyte.4,5 Centrilobular necrosis has been observed in animals anesthetized with halothane under hypoxic conditions after pretreatment with enzyme-inducing agents.6,7 In human beings, two different. © 1980, Massachusetts Medical Society. All rights reserved.