Mechanism, pathology, and clinical presentation of hepatotoxicity of anesthetic agents

Drug-Induced Liver Disease, Second Edition

Volumn , Issue , 2007, Pages 465-484

  Kenna, J Gerald ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 79953294623     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (155)

1. Zimmerman HJ. Anesthetic Agents. Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. New York: Appleton-Century-Crofts, 1978:370-94.
2. Pohl LR. Biochemical toxicology of chloroform. Rev Biochem Toxicol 1979; 1:79-107.
3. Inman WH, Mushin WW. Jaundice after repeated exposure to halothane: an analysis of Reports to the Committee on Safety of Medicines. Br Med J 1974; 1:5-10.
4. Ray DC, Drummond GB. Halothane hepatitis. Br J Anaesth 1991; 67:84-99.
5. Kenna JG, Neuberger J. Immunopathogenesis and treatment of halothane hepatitis. Clin Immunother 1995; 3:108-24.
6. Bunker JP. Final report of the National Halothane Study. Anesthesiology 1968; 29:231-2.
7. Kenna JG, Neuberger J, Mieli-Vergani G, Mowat AP, Williams R. Halothane hepatitis in children. Br Med J (Clin Res Ed) 1987; 294:1209-11.
8. Neuberger J, Vergani D, Mieli-Vergani G, Davis M, Williams R. Hepatic damage after exposure to halothane in medical personnel. Br J Anaesth 1981; 53:1173-7.
9. Klion FM, Schaffner F, Popper H. Hepatitis after exposure to halothane. Ann Intern Med 1969; 71:467-77.
10. Moult PJ, Sherlock S. Halothane-related hepatitis: a clinical study of twenty-six cases. Q J Med 1975; 44:99-114.
11. Kenna JG, Neuberger J, Williams R. Specific antibodies to halothane-induced liver antigens in halothane-associated hepatitis. Br J Anaesth 1987; 59:1286-90.
12. Benjamin SB, Goodman ZD, Ishak KG, Zimmerman HJ, Irey NS. The morphologic spectrum of halothane-induced hepatic injury: analysis of 77 cases. Hepatology 1985; 5:1163-71.
13. Uzunalimoglu B, Yardley JH, Boitnott JK. The liver in mild halothane hepatitis. Light and electron microscopic findings with special reference to the mononuclear cell infiltrate. Am J Pathol 1970; 61:457-78.
14. Wills EJ, Walton B. A morphologic study of unexplained hepatitis following halothane anesthesia. Am J Pathol 1978; 91:11-32.
15. Martin JL, Dubbink DA, Plevak DJ, et al. Halothane hepatitis 28 years after primary exposure. Anesth Analg 1992; 74:605-8.
16. Inman WH, Mushin WW. Jaundice after repeated exposure to halothane: a further analysis of reports to the Committee on Safety of Medicines. Br Med J 1978; 2:1455-6.
17. Walton B, Simpson BR, Strunin L, Doniach D, Perrin J, Appleyard AJ. Unexplained hepatitis following halothane. Br Med J 1976; 1:1171-6.
18. Wright R, Eade OE, Chisholm M, et al. Controlled prospective study of the effect on liver function of multiple exposures to halothane. Lancet 1975; 1:817-20.
19. Trowell J, Peto R, Smith AC. Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium. Lancet 1975; 1:821-4.
20. Davis M, Eddleston AL, Neuberger JM, Vergani D, Mieli-Vergani G, Williams R. Halothane hepatitis. N Engl J Med 1980; 303:1123-4 (letter).
21. Sakaguchi Y, Inaba S, Irita K, Sakai H, Nawata H, Takahashi S. Absence of antitrifluoro-acetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage. Can J Anaesth 1994; 41:398-403.
22. Lewis JH, Zimmerman HJ, Ishak KG, Mullick FG. Enflurane hepatotoxicity: a clinicopathologic study of 24 cases. Ann Intern Med 1983; 98:984-92.
23. Brown BR, Jr., Gandolfi AJ. Adverse effects of volatile anaesthetics. Br J Anaesth 1987; 59:14-23.
24. Sigurdsson J, Hreidarsson AB, Thjodleifsson B. Enflurane hepatitis: a report of a case with a previous history of halothane hepatitis. Acta Anaesthesiol Scand 1985; 29:495-6.
25. Gogus FY, Toker K, Baykan N. Hepatitis following use of two different fluorinated anesthetic agents. Isr J Med Sci 1991; 27:156-9.
26. Brunt EM, White H, Marsh JW, Holtmann B, Peters MG. Fulminant hepatic failure after repeated exposure to isoflurane anesthesia: a case report. Hepatology 1991; 13:1017-21.
27. Sinha A, Clatch RJ, Stuck G, Blumenthal SA, Patel SA. Isoflurane hepatotoxicity: a case report and review of the literature. Am J Gastroenterol 1996; 91:2406-9.
28. Weitz J, Kienle P, Bohrer H, Hofmann W, Theilmann L, Otto G. Fatal hepatic necrosis after isoflurane anaesthesia. Anaesthesia 1997; 52:892-5.
29. Turner GB, O’Rourke D, Scott GO, Beringer TR. Fatal hepatotoxicity after re-exposure to isoflurane:a case report and review of the literature. Eur J Gastroenterol Hepatol 2000; 12:955-9.
30. Zimmerman H. Even isoflurane. Hepatology 1991; 13:1251-3 (editorial).
31. Gunaratnam NT, Benson J, Gandolfi AJ, Chen M. Suspected isoflurane hepatitis in an obese patient with a history of halothane hepatitis. Anesthesiology 1995; 83:1361-4.
32. Meldrum DJ, Griffiths R, Kenna JG. Gallstones and isoflurane hepatitis. Anaesthesia 1998; 53:905-9.
33. Martin JL, Plevak DJ, Flannery KD, et al. Hepatotoxicity after desflurane anesthesia. Anesthesiology 1995; 83:1125-9.
34. Ogawa M, Doi K, Mitsufuji T, Satoh K, Takatori T. Drug induced hepatitis following sevoflurane anesthesia in a child. Masui 1991; 40:1542-5.
35. Shichinohe Y, Masuda Y, Takahashi H, et al. A case of postoperative hepatic injury after sevoflurane anesthesia. Masui 1992; 41:1802-5.
36. Jang Y, Kim I. Severe hepatotoxicity after sevoflurane anesthesia in a child with mild renal dysfunction. Pediatr Anesth 2005; 15:1140-4.
37. Chung PC, Chiou SC, Lien JM, Li AH, Wong CH. Reproducible hepatic dysfunction following separate anesthesia with sevoflurane and desflurane. Chang Gung Med J 2003; 26:357-62.
38. Varma RR, Whitesell RC, Iskandarani MM. Halothane hepatitis without halothane: role of inapparent circuit contamination and it prevention. Hepatology 1985; 5:1159-62.
39. Rehder K, Forbes J, Alter H, Hessler O, Stier A. Halothane biotransformation in man: a quantitative study. Anesthesiology 1967; 28:711-5.
40. Kenna JG, van Pelt FNAM. The metabolism and toxicity of inhaled anaesthetic agents. Anaesth Pharmacol Rev 1994; 2:29-42.
41. Cohen EN. Metabolism of the volatile anesthetics. Anesthesiology 1971; 35:193-202.
42. Gandolfi AJ, White RD, Sipes IG, Pohl LR. Bioactivation and covalent binding of halothane in vitro:studies with [3H]- and [14C]halothane. J Pharmacol Exp Ther 1980; 214:721-5.
43. Satoh H, Fukuda Y, Anderson DK, Ferrans VJ, Gillette JR, Pohl LR. Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical evidence of trifluoroacetylated hepatocytes. J Pharmacol Exp Ther 1985; 233:857-62.
44. Trudell JR, Ardies CM, Anderson WR. Antibodies raised against trifluoroacetyl-protein adducts bind to N-trifluoroacetyl-phosphatidylethanolamine in hexagonal phase phospholipid micelles. J Pharmacol Exp Ther 1991; 257:657-62.
45. Kharasch ED, Hankins DC, Fenstamaker K, Cox K. Human halothane metabolism, lipid peroxidation, and cytochromes P(450)2A6 and P(450)3A4. Eur J Clin Pharmacol 2000; 55:853-9.
46. Kharasch ED, Hankins D, Mautz D, Thummel KE. Identification of the enzyme responsible for oxidative halothane metabolism: implications for prevention of halothane hepatitis. Lancet 1996; 347:1367-71.
47. Eliasson E, Gardner I, Hume-Smith H, de Waziers I, Beaune P, Kenna JG. Interindividual variability in P450-dependent generation of neoantigens in halothane hepatitis. Chem Biol Interact 1998; 116:123-41.
48. Kharasch ED, Thummel KE, Mautz D, Bosse S. Clinical enflurane metabolism by cytochrome P450 2E1. Clin Pharmacol Ther 1994; 55:434-40.
49. Kharasch ED, Hankins DC, Cox K. Clinical isoflurane metabolism by cytochrome P450 2E1. Anesthesiology 1999; 90:766-71.
50. Chase RE, Holaday DA, Fiserova-Bergerova V, Saidman LJ, Mack FE. The biotransformation of ethrane in man. Anesthesiology 1971; 35:262-7.
51. Holaday DA, Fiserova-Bergerova V, Latto IP, Zumbiel MA. Resistance of isoflurane to biotransformation in man. Anesthesiology 1975; 43:325-32.
52. Fiserova-Bergerova V, Holaday DA. Uptake and clearance of inhalation anesthetics in man. Drug Metab Rev 1979; 9:43-60.
53. Burke TR, Jr., Branchflower RV, Lees DE, Pohl LR. Mechanism of defluorination of enflurane:identification of an organic metabolite in rat and man. Drug Metab Dispos 1981; 9:19-24.
54. Christ DD, Satoh H, Kenna JG, Pohl LR. Potential metabolic basis for enflurane hepatitis and the apparent cross-sensitization between enflurane and halothane. Drug Metab Dispos 1988; 16:135-40.
55. Hitt BA, Mazze RI, Cousins MJ, Edmunds HN, Barr GA, Trudell JR. Metabolism of isoflurane in Fischer 344 rats and man. Anesthesiology 1974; 40:62-7.
56. Sutton TS, Koblin DD, Gruenke LD, et al. Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. Anesth Analg 1991; 73:180-5.
57. Cook TL, Beppu WJ, Hitt BA, Kosek JC, Mazze RI. Renal effects and metabolism of sevoflurane in Fisher 3444 rats: an in-vivo and in-vitro comparison with methoxyflurane. Anesthesiology 1975; 43:70-7.
58. Holaday DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers. Anesthesiology 1981; 54:100-6.
59. Kharasch ED. Biotransformation of sevoflurane. Anesth Analg 1995; 81:S27-38.
60. Hanaki C, Fujii K, Mario M, Tashima T. Decomposition of sevoflurane by soda lime. Hiroshima J Med Sci 1987; 36:61-7.
61. Jin L, Davis MR, Kharasch ED, Doss GA, Baillie T. Identification in rat bile of glutathione conjugates of fluoromethyl 2,2-difluoro-1-(trifluoromethyl) vinyl ether, a nephrotoxic degradate of the anesthetic agent sevoflurane. Chem Res Toxicol 1996; 9:555-61.
62. Spracklin D, Kharasch ED. Evidence for the metabolism of fluoromethyl 2,2-difluoro-1-(trifluoromethyl) vinyl ether (Compound A) by cysteine conjugate β-lyase in rats. Chem Res Toxicol 1996; 9:696-702.
63. Iyer RA, Frink EJ, Jr., Ebert TJ, Anders MW. Cysteine conjugate β-lyase dependent metabolism of compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in human subjects anesthetized with sevoflurane and in rats given compound A. Anesthesiology 1998; 88:611-8.
64. Altuntas TG, Park SB, Kharasch ED. Sulfoxidation of cysteine and mercapturic acid conjugates of the sevoflurane degradation product fluoromethyl 2,2-difluoro-1-(trifluoromethyl) vinyl ether (Compound A). Chem Res Toxicol 2004; 17:435-45.
65. Sheffels P, Schroeder JL, Altunatas TG, Liggitt HD, Kharasch ED. Role of cytochrome P4503A in cysteine S-conjugates sulfoxidation and the nephrotoxicity of the sevoflurane degradation product fluoromethyl 2,2-difluoro-1-(trifluoromethyl) vinyl ether (Compound A) in rats. Chem Res Toxicol 2004; 17:1177-89.
66. Reynolds ES, Moslen MT. Halothane hepatotoxicity: enhancement by polychlorinated biphenyl pretreatment. Anesthesiology 1977; 47:19-27.
67. McLain GE, Sipes IG, Brown BR, Jr. An animal model of halothane hepatotoxicity: roles of enzyme induction and hypoxia. Anesthesiology 1979; 51:321-6.
68. Cousins MJ, Sharp JH, Gourlay GK, Adams JF, Haynes WD, Whitehead R. Hepatotoxicity and halothane metabolism in an animal model with application for human toxicity. Anaesth Intens Care 1979; 7:9-24.
69. Pohl LR, Gillette JR. A perspective on halothane-induced hepatotoxicity. Anesth Analg 1982; 61:809-11 (letter).
70. Clarke JB, Gandolfi AJ. Volatile anesthetics: mechanisms of potential hepatotoxicity. Clin Anesth Updates 1992; 3:1-11.
71. Berman ML, Kuhnert L, Phythyon JM, Holaday DA. Isoflurane and enflurane-induced hepatic necrosis in triiodothyronine-pretreated rats. Anesthesiology 1983; 58:1-5.
72. Rice SA, Maze M, Smith CM, Kosek JC, Mazze RI. Halothane hepatotoxicity in Fischer 344 rats pretreated with isoniazid. Toxicol Appl Pharmacol 1987; 87:411-9.
73. Lunam CA, Cousins MJ, Hall PD. Guinea-pig model of halothane-associated hepatotoxicity in the absence of enzyme induction and hypoxia. J Pharmacol Exp Ther 1985; 232:802-9.
74. Lind RC, Gandolfi AJ, Hall PD. The role of oxidative biotransformation of halothane in the guinea pig model of halothane-associated hepatotoxicity. Anesthesiology 1989; 70:649-53.
75. Farrell GC, Frost L, Tapner M, Field J, Weltman M, Mahoney J. Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow. J Gastroenterol Hepatol 1996; 11:594-601.
76. Lind RC, Gandolfi AJ, Hall PM. Glutathione depletion enhances subanesthetic halothane hepatotoxicity in guinea pigs. Anesthesiology 1992; 77:721-7.
77. de Groot H, Noll T. Halothane hepatotoxicity: relation between metabolic activation, hypoxia, covalent binding, lipid peroxidation and liver cell damage. Hepatology 1983; 3:601-6.
78. Odaka Y, Takahashi T, Yamasaki A, et al. Prevention of halothane-induced hepatotoxicity by hemin pretreatment. Protective role of heme oxygenase-1 induction. Biochem Pharmacol 2000; 59:871-80.
79. Goto T, Ohwan K, Matsumoto N, et al. Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats. Masui 1990; 39:204-9.
80. Farrell GC, Mahoney J, Bilous M, Frost L. Altered hepatic calcium homeostasis in guinea pigs with halothane-induced hepatotoxicity. J Pharmacol Exp Ther 1988; 247:751-6.
81. Frost L, Mahoney J, Field J, Farrell GC. Impaired bile flow and disordered hepatic calcium homeostasis are early features of halothane-induced liver injury in guinea pigs. Hepatology 1996; 23:80-6.
82. Bourdi M, Reilly TP, Elkahloun AG, George JW, Pohl LR. Macrophage migration inhibitory factor in drug-induced liver injury: a role in susceptibility and stress responsiveness. Biochem Biophys Res Comm 2002; 294:225-30.
83. Bourdi M, Amouzadeh HR, Rushmore TH, Martin JL, Pohl LR. Halothane-induced liver injury in outbred guinea pigs: role of trifluoroacetylated protein adducts in animal susceptibility. Chem Res Toxicol 2001; 14:362-70.
84. Van Dyke RA. Hepatic centrilobular necrosis in rats after exposure to halothane, enflurane, or isoflurane. Anesth Analg 1982; 61:812-9.
85. Harper MH, Collins P, Johnson B, Eger EI II, Biava C. Hepatic Injury following halothane, enflurane, and isoflurane anesthesia in rats. Anesthesiology 1982; 56:14-7.
86. Shingu K, Eger EI II, Johnson BH, et al. Hepatic injury induced by anesthetic agents in rats. Anesth Analg 1983; 62:140-5.
87. Gonsowski CT, Laster MJ, Eger EI II, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of increasing duration of administration. Anesthesiology 1994; 80:566-73.
88. Keller KA, Callan C, Prokocimer P, et al. Inhalation toxicology study of a haloalkene degradant of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats. Anesthesiology 1995; 83:1220-32.
89. Kharasch ED, Hoffman GM, Thorning D, Hankins DC, Kilty CG. Role of the cysteine conjugate β-lyase pathway in inhaled compound A nephrotoxicity in rats. Anesthesiology 1998; 88:1624-33.
90. Obata R, Bito H, Ohmura M, et al. The effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic function. Anesth Analg 2000; 91:1262-8.
91. Vergani D, Tsantoulas D, Eddleston AL, Davis M, Williams R. Sensitisation to halothane-altered liver components in severe hepatic necrosis after halothane anaesthesia. Lancet 1978; 2:801-3.
92. Vergani D, Mieli-Vergani G, Alberti A, et al. Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis. N Engl J Med 1980; 303:66-71.
93. Neuberger J, Gimson AE, Davis M, Williams R. Specific serological markers in the diagnosis of fulminant hepatic failure associated with halothane anaesthesia. Br J Anaesth 1983; 55:15-9.
94. Kenna JG, Neuberger J, Williams R. An enzyme-linked immunosorbent assay for detection of antibodies against halothane-altered hepatocyte antigens. J Immunol Methods 1984; 75:3-14.
95. Kenna JG, Neuberger J, Williams R. Identification by immunoblotting of three halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis. J Pharmacol Exp Ther 1987; 242:733-40.
96. Kenna JG, Neuberger J, Williams R. Evidence for expression in human liver of halothane-induced neoantigens recognized by antibodies in sera from patients with halothane hepatitis. Hepatology 1988; 8:1635-41.
97. Kenna JG, Satoh H, Christ DD, Pohl LR. Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group derived from halothane. J Pharmacol Exp Ther 1988; 245:1103-9.
98. Kenna JG, Martin JL, Satoh H, Pohl LR. Factors affecting the expression of trifluoroacetylated liver microsomal protein neoantigens in rats treated with halothane. Drug Metab Dispos 1990; 18:788-93.
99. Harris JW, Pohl LR, Martin JL, Anders MW. Tissue acylation by the chlorofuorocarbon substitute 2,2- dichloro-1,1,1-trifluoroethane. Proc Natl Acad Sci USA 1991; 88:1407-10.
100. Heijink E, De Matteis F, Gibbs AH, Davies A, White IN. Metabolic activation of halothane to neoantigens in C57B1/10 mice: immunochemical studies. Eur J Pharmacol 1993; 248:15-25.
101. Knight TL, Scatchard KM, Van Pelt FN, Kenna JG. Sera from patients with halothane hepatitis contain antibodies to halothane-induced liver antigens which are not detectable by immunoblotting. J Pharmacol Exp Ther 1994; 270:1325-33 (published erratum appears in J Pharmacol Exp Ther 1995; 272(2):962).
102. Ramsay L, Barnes S, Gardner I, Eliasson E, Kenna JG. Identification by immunoprecipitation of novel halothane-induced protein antigens recognised by antibodies from patients with halothane hepatitis. Br J Clin Pharmacol 1998; 46:303P-4P.
103. Kenna JG, Martin JL, Pohl LR. The topography of trifluoroacetylated protein antigens in liver microsomal fractions from halothane treated rats. Biochem Pharmacol 1992; 44:621-9.
104. Brown AP, Gandolfi AJ. Glutathione-S-transferase is a target for covalent modification by a halothane reactive intermediate in the guinea pig liver. Toxicology 1994; 89:35-47.
105. Eliasson E, Kenna JG. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol Pharmacol 1996; 50:573-82.
106. Bourdi M, Chen W, Peter RM, et al. Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem Res Toxicol 1996; 9:1159-66.
107. Martin JL, Kenna JG, Martin BM, Thomassen D, Reed GF, Pohl LR. Halothane hepatitis patients have serum antibodies that react with protein disulfide isomerase. Hepatology 1993; 18:858-63.
108. Martin JL, Reed GF, Pohl LR. Association of anti-58 kDa endoplasmic reticulum antibodies with halothane hepatitis. Biochem Pharmacol 1993; 46:1247-50.
109. Satoh H, Martin BM, Schulick AH, Christ DD, Kenna JG, Pohl LR. Human antiendoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase. Proc Natl Acad Sci USA 1989; 86:322-6.
110. Butler LE, Thomassen D, Martin JL, Martin BM, Kenna JG, Pohl LR. The calcium-binding protein calreticulin is covalently modified in rat liver by a reactive metabolite of the inhalation anesthetic halothane. Chem Res Toxicol 1992; 5:406-10.
111. Pumford NR, Martin BM, Thomassen D, et al. Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein ERp72. Chem Res Toxicol 1993; 6:609-15.
112. Davila JC, Martin BM, Pohl LR. Patients with halothane hepatitis have serum antibodies directed against glucose-regulated stress protein GRP78/BiP. Toxicologist 1992; 12:255.
113. Thomassen D, Martin BM, Martin JL, Pumford NR, Pohl LR. The role of a stress protein in the development of a drug-induced allergic response. Eur J Pharmacol 1990; 183:1138-9.
114. Amouzadeh HR, Bourdi M, Martin JL, Martin BM, Pohl LR. UDP-glucose:glycoprotein glucosyltrasferase associates with endoplasmic reticulum chaperones and its activity is decreased in vivo by the inhalation anesthetic halothane. Chem Res Toxicol 1997; 10:59-63.
115. Vidali M, Hidestrand M, Eliasson E, et al. Use of molecular simulation for mapping conformational CYP2E1 epitopes. J Biol Chem 2004; 279:50949-55.
116. Pohl LR, Thomassen D, Pumford NR, et al. Hapten carrier conjugates associated with halothane hepatitis. Adv Exp Med Biol 1991; 283:111-20.
117. Martin JL, Kenna JG, Pohl LR. Antibody assays for the detection of patients sensitized to halothane. Anesth Analg 1990; 70:154-9.
118. Smith GC, Kenna JG, Harrison DJ, Tew D, Wolf CR. Autoantibodies to hepatic microsomal carboxylesterase in halothane hepatitis. Lancet 1993; 342:963-4.
119. Kitteringham NR, Kenna JG, Park BK. Detection of autoantibodies directed against human hepatic endoplasmic reticulum in patients with halothane-associated hepatitis. Br J Clin Pharmacol 1995; 40:379-86.
120. Neuberger J, Kenna JG. Halothane hepatitis: a model of immunoallergic hepatitis. In: Guillouzo A, ed. Liver Cells and Drugs Paris & London: John Libbey Eurotext Ltd, 1988:161-73.
121. Njoku DB, Greenberg RS, Bourdi M, et al. Antoantibodies associated with volatile anesthetic hepatitis found in the sera of a large cohort of pediatric anesthesiologists. Anesth Analg 2002; 94:243-9.
122. Ellgaard L, Helenius A. Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 2003; 4:181-91.
123. Robin MA, Descatoire V, Le Roy M, et al. Vesicular transport of newly synthesized cytochromes P4501A to the outside of rat hepatocyte plasma membranes. J Pharmacol Exp Ther 2000; 294:1063-9.
124. Neve EP, Ingelman-Sundberg M. Molecular basis for the transport of cytochrome P450 2E1 to the plasma membrane. J Biol Chem 2000; 275:17130-5.
125. Zhu Q, von Dippe P, Xing W, Levy D. Membrane topology and cell surface targeting of microsomal epoxide hydrolase. Evidence for multiple topological orientations. J Biol Chem 1999; 274:27898-904.
126. Christ DD, Kenna JG, Kammerer W, Satoh H, Pohl LR. Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis. Anesthesiology 1988; 69:833-8.
127. Njoku D, Laster MJ, Gong DH, Eger El II, Reed GF, Martin JL. Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylatioan and hepatic injury. Anesth Analg 1997; 84:173-8.
128. Harris JW, Jones JP, Martin JL, et al. Pentahaloethane-based chlorofluorocarbon substitutes and halothane: correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation. Chem Res Toxicol 1992; 5:720-5.
129. Marit GB, Dodd DE, George ME, Vinegar A. Hepatotoxicity in guinea pigs following acute inhalation exposure to 1,1-dichloro-2,2,2-trifluoroethane. Toxicol Pathol 1994; 22:404-14.
130. Hoet P, Graf ML, Bourdi M, et al. Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons. Lancet 1997; 350:556-9.
131. Callis AK, Brooks SD, Roth TP, Gandolfi AJ, Bown BR. Characterization of a halothane-induced humoral immune responses in rabbits. Clin Exp Immunol 1987; 67:343-51.
132. Roth TP, Hubbard AK, Gandolfi AJ, Brown BR. Chronology of halothane-induced antigen expression in halothane-exposed rabbits. Clin Exp Immunol 1988; 72:330-6.
133. Siadat-Pajouh M, Hubbard AK, Roth TP, Gandolfi AJ. Generation of halothane-induced immune response in a guinea pig model of halothane hepatitis. Anesth Analg 1987; 66:1209-14.
134. Furst SM, Luedke D, Gaw HH, Reich R, Gandolfi AJ. Demonstration of a cellular immune response in halothane-exposed guinea pigs. Toxicol Appl Pharmacol 1997; 143:245-55.
135. Mathieu A, Dipadua D, Kahan BD, Galdabini JJ, Mills J. Correlation between specific immunity to a metabolite of halothane and hepatic lesions after multiple exposures. Anesth Analg 1975; 54:332-9.
136. Neuberger J, Kenna JG, Williams R. Halothane hepatitis: attempt to develop an animal model. Int J Immunopharmacol 1987; 9:123-32.
137. Hastings KL, Thomas C, Brown AP, Gandolfi AJ. Trifluoroacetylation potentiates the humoral immune response to halothane in the guinea pig. Immunopharmacol Immunotoxicol 1995; 17:201-13.
138. Zheng XH, Begay C, Lind RC, Gandolfi AJ. Humoral immune response to a sevoflurane degradation product in the guinea pig following inhalation exposure. Drug Chemical Toxicol 2001; 24:339-46.
139. Allison AC. Theories of self tolerance and autoimmunity. In: Kammuller ME, Bloksma N, Seinen W, eds. Autoimmunity and Toxicology: Immune Dysregulation Induced by Drugs and Chemicals. Amsterdam: Elsevier, 1989:67-115.
140. O’Shea D, Davis SN, Kim RB, Wilkinson GR. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther 1994; 56:359-67.
141. Young SR, Stoelting RK, Peterson C, Madura JA. Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia. Anesthesiology 1975; 42:451-7.
142. Farrell G, Prendergast D, Murray M. Halothane hepatitis. Detection of a constitutional susceptibility factor. N Engl J Med 1985; 313:1310-4.
143. Hoft RH, Bunker JP, Goodman HI, Gregory PB. Halothane hepatitis in three pairs of closely related women. N Engl J Med 1981; 304:1023-4.
144. Otsuka S, Yamamoto M, Kasuya S, et al. HLA antigens in patients with unexplained hepatitis following halothane anesthesia. Acta Anaesthesiol Scand 1985; 29:497-501.
145. Eade OE, Grice D, Krawitt EL, et al. HLA A and B locus antigens in patients with unexplained hepatitis following halothane anaesthesia. Tissue Antigens 1981; 17:428-32.
146. Gut J, Christen U, Frey N, Koch V, Stoffler D. Molecular mimicry in halothane hepatitis: biochemical and structural characterization of lipoylated autoantigens. Toxicology 1995; 97:199-224.
147. Christen U, Quinn J, Yeaman SJ, et al. Identification of the dihydrolipoamide acetyltransferase subunit of the human pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis. Molecular mimicry of trifluoroacetyl-lysine by lipoic acid. Eur J Biochem 1994; 223:1035-47.
148. Frey N, Christen U, Jeno P, et al. The lipoic acid containing components of the 2-oxoacid dehydrogenase complexes mimic trifluoroacetylated proteins and are autoantigens associated with halothane hepatitis. Chem Res Toxicol 1995; 8:736-46.
149. Gut J, Christen U, Huwyler J, Burgin M, Kenna JG. Molecular mimicry of trifluoroacetylated human liver protein adducts by constitutive proteins and immunochemical evidence for its impairment in halothane hepatitis. Eur J Biochem 1992; 210:569-76.
150. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12:991-1045.
151. Park BK, Pirmohamed M, Kitteringham NR. Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective. Chem Res Toxicol 1998; 11:969-88.
152. Uetrecht JP. New concepts in immunology relevant to idiosyncratic drug reactions: the “Danger Hypothesis” and innate immune system. Chem Res Toxicol 1999; 12:387-95.
153. Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol 2003; 3:51-62.
154. Bowen DG, Zen M, Holz L, Davis T, McCaughan GW, Bertolino P. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity. J Clin Invest 2004; 114:701-12.
155. Bowen DG, McCaughan GW, Bertolino P. Intrahepatic immunity: a tale of two sites? Trends Immunol 2005; 26:512-7.