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Halothane hepatitis

Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF


Inhaled anesthetics were first used in the mid-1800s with the discovery of diethyl ether [1,2]. Prior to the 1950s, ether and chloroform were used exclusively. The first halogenated anesthetic, halothane, was introduced into use in 1956, and rapidly replaced both ether and chloroform as the surgical anesthetic of choice [3,4]. Isolated case reports of severe hepatitis were soon reported [5-9]. In 1969, the National Institutes of Health organized one of the largest epidemiological studies ever performed in the United States to evaluate halothane toxicity. A review of 250,000 cases of halothane use revealed an incidence of fatal hepatic necrosis of approximately 1 in 35,000 exposures [10]. A similar large-scale review in the United Kingdom showed nearly identical results [11]. Less and less hepatotoxic alternatives have been serially introduced: enflurane (1972), isoflurane (1981), desflurane (1992) and sevoflurane (1995) [12,13]. However, reports of hepatotoxicity with these medications also exist [14-27].

Concern about hepatotoxicity has virtually eliminated the use of halothane in adults in the United States. Initially, toxicity to halothane was not reported in children. Subsequent reports, however, demonstrated that the incidence of halothane-associated hepatitis in children is between 1 in 82,000 and 1 in 200,000 [28-33]. Halothane use in children has been largely replaced by sevoflurane [34]. The reason for the lower incidence of halothane-associated hepatitis observed in children is unclear [35,36]. Worldwide, halothane is possibly the most commonly used inhalational anesthetic [37], and reports of hepatotoxicity continue to be published [38-41].

Approximately 60 to 80 percent of the inhaled anesthetics are eliminated unchanged via the respiratory system [42]. However, their lipophilic nature allows some systemic absorption. This portion of anesthetic must then be detoxified, a process occurring predominantly within the liver. The nontoxic product is then excreted in the urine.

This topic will review hepatotoxicity related to halothane. Hepatotoxicity related to other medications, herbs, and dietary supplements is discussed separately. (See "Drug-induced liver injury" and "Hepatotoxicity due to herbal medications and dietary supplements".)


Halothane is associated with two clinical patterns of liver injury: hepatotoxicity and hepatitis [40,43-48].


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  1. Eger EI 2nd. Current and future perspectives on inhaled anesthetics. Pharmacotherapy 1998; 18:895.
  2. Eger EI 2nd. Characteristics of anesthetic agents used for induction and maintenance of general anesthesia. Am J Health Syst Pharm 2004; 61 Suppl 4:S3.
  3. JOHNSTONE M. The human cardiovascular response to fluothane anaesthesia. Br J Anaesth 1956; 28:392.
  4. SUCKLING CW. Some chemical and physical factors in the development of fluothane. Br J Anaesth 1957; 29:466.
  5. Virtue RW, Payne KW. Postoperative death after Fluothane. Anesthesiology 1958; 19:562.
  6. LINDENBAUM J, LEIFER E. Hepatic necrosis associated with halothane anesthesia. N Engl J Med 1963; 268:525.
  7. BRODY GL, SWEET RB. Halothane anesthesia as a possible cause of massive hepatic necrosis. Anesthesiology 1963; 24:29.
  8. HEIDENBERG WJ, TORIO I. Additional case of halothane hepatitis. N Engl J Med 1963; 268:1090.
  10. Bunker JP, Forrest WH, Mosteller F, et al (Eds).. National Halothane Study. A study of the possible association between halothane anesthesia and postoperative hepatic necrosis. U.S. Government Printing Office, Washington, DC 1969.
  11. Walton B, Simpson BR, Strunin L, et al. Unexplained hepatitis following halothane. Br Med J 1976; 1:1171.
  12. Black GW, Clarke RS. Recently introduced anesthetic drugs. Int Anesthesiol Clin 1971; 9:171.
  13. Stevens WC. New halogenated anesthetics: enflurane and isoflurane. Calif Med 1972; 117:47.
  14. Stachnik J. Inhaled anesthetic agents. Am J Health Syst Pharm 2006; 63:623.
  15. Ihtiyar E, Algin C, Haciolu A, Isiksoy S. Fatal isoflurane hepatotoxicity without re-exposure. Indian J Gastroenterol 2006; 25:41.
  16. White LB, DeTarnowsky GO, Mir JA, Layden TJ. Hepatotoxicity following enflurane anesthesia. Dig Dis Sci 1981; 26:466.
  17. Paull JD, Fortune DW. Hepatotoxicity and death following two enflurane anaesthetics. Anaesthesia 1987; 42:1191.
  18. Weitz J, Kienle P, Böhrer H, et al. Fatal hepatic necrosis after isoflurane anaesthesia. Anaesthesia 1997; 52:892.
  19. Martin JL, Plevak DJ, Flannery KD, et al. Hepatotoxicity after desflurane anesthesia. Anesthesiology 1995; 83:1125.
  20. Tung D, Yoshida EM, Wang CS, Steinbrecher UP. Severe desflurane hepatotoxicity after colon surgery in an elderly patient. Can J Anaesth 2005; 52:133.
  21. Singhal S, Gray T, Guzman G, et al. Sevoflurane hepatotoxicity: a case report of sevoflurane hepatic necrosis and review of the literature. Am J Ther 2010; 17:219.
  22. Turillazzi E, D'Errico S, Neri M, et al. A fatal case of fulminant hepatic necrosis following sevoflurane anesthesia. Toxicol Pathol 2007; 35:840.
  23. Christ DD, Kenna JG, Kammerer W, et al. Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis. Anesthesiology 1988; 69:833.
  24. Carrigan TW, Straughen WJ. A report of hepatic necrosis and death following isoflurane anesthesia. Anesthesiology 1987; 67:581.
  25. Chase RE, Holaday DA, Fiserova-Bergerova V, et al. The biotransformation of ethrane in man. Anesthesiology 1971; 35:262.
  26. Lewis JH, Zimmerman HJ, Ishak KG, Mullick FG. Enflurane hepatotoxicity. A clinicopathologic study of 24 cases. Ann Intern Med 1983; 98:984.
  27. Sinha A, Clatch RJ, Stuck G, et al. Isoflurane hepatotoxicity: a case report and review of the literature. Am J Gastroenterol 1996; 91:2406.
  28. Carney FM, Van Dyke RA. Halothane hepatitis: a critical review. Anesth Analg 1972; 51:135.
  29. Warner LO, Beach TP, Garvin JP, Warner EJ. Halothane and children: the first quarter century. Anesth Analg 1984; 63:838.
  30. Munro HM, Snider SJ, Magee JC. Halothane-associated hepatitis in a 6-year-old boy: evidence for native liver regeneration following failed treatment with auxiliary liver transplantation. Anesthesiology 1998; 89:524.
  31. Lewis RB, Blair M. Halothane hepatitis in a young child. Br J Anaesth 1982; 54:349.
  32. Kenna JG, Neuberger J, Mieli-Vergani G, et al. Halothane hepatitis in children. Br Med J (Clin Res Ed) 1987; 294:1209.
  33. Vorrakitpokatorn P, Limsakul A. Drug-induced hyperthermia and rhabdomyolysis during the perioperative period: report of three patients. J Med Assoc Thai 2002; 85 Suppl 3:S884.
  34. Goa KL, Noble S, Spencer CM. Sevoflurane in paediatric anaesthesia: a review. Paediatr Drugs 1999; 1:127.
  35. Wark H, Earl J, Chau DD, Overton J. Halothane metabolism in children. Br J Anaesth 1990; 64:474.
  36. Gallagher TM, Black GW. Uptake of volatile anaesthetics in children. Anaesthesia 1985; 40:1073.
  37. Wiklund RA, Rosenbaum SH. Anesthesiology. First of two parts. N Engl J Med 1997; 337:1132.
  38. Qureshi MA, Saeed F, Hussain T. Halothane induced fulminant hepatic failure. J Coll Physicians Surg Pak 2007; 17:103.
  39. Kumar GP, Bhat VJ, Sowdi V. Fulminant hepatic failure following halothane anaesthesia. J Clin Forensic Med 2005; 12:271.
  40. Otedo AE. Halothane induced hepatitis: case report. East Afr Med J 2004; 81:538.
  41. Eghtesadi-Araghi P, Sohrabpour A, Vahedi H, Saberi-Firoozi M. Halothane hepatitis in Iran: a review of 59 cases. World J Gastroenterol 2008; 14:5322.
  42. Soleimanpour H, Safari S, Rahmani F, et al. The role of inhalational anesthetic drugs in patients with hepatic dysfunction: a review article. Anesth Pain Med 2015; 5:e23409.
  43. Brown BR Jr, Gandolfi AJ. Adverse effects of volatile anaesthetics. Br J Anaesth 1987; 59:14.
  44. Liu ZX, Kaplowitz N. Immune-mediated drug-induced liver disease. Clin Liver Dis 2002; 6:755.
  45. Lo SK, Wendon J, Mieli-Vergani G, Williams R. Halothane-induced acute liver failure: continuing occurrence and use of liver transplantation. Eur J Gastroenterol Hepatol 1998; 10:635.
  46. Kharasch ED. Adverse drug reactions with halogenated anesthetics. Clin Pharmacol Ther 2008; 84:158.
  47. Bond GR. Hepatitis, rash and eosinophilia following trichloroethylene exposure: a case report and speculation on mechanistic similarity to halothane induced hepatitis. J Toxicol Clin Toxicol 1996; 34:461.
  48. Kenna JG. The molecular basis of halothane-induced hepatitis. Biochem Soc Trans 1991; 19:191.
  49. 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.
  50. 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.
  51. Safari S, Motavaf M, Seyed Siamdoust SA, Alavian SM. Hepatotoxicity of halogenated inhalational anesthetics. Iran Red Crescent Med J 2014; 16:e20153.
  52. Fee JP, Thompson GH. Comparative tolerability profiles of the inhaled anaesthetics. Drug Saf 1997; 16:157.
  53. Zimmerman HJ. Hepatotoxicity. The adverse effects of drugs and other chemicals on the liver, Appleton-Century-Crofts, New York 1978.
  54. Mushin WW, Rosen M, Jones EV. Post-halothane jaundice in relation to previous administration of halothane. Br Med J 1971; 3:18.
  55. Gut J. Molecular basis of halothane hepatitis. Arch Toxicol Suppl 1998; 20:3.
  56. Summary of the national Halothane Study. Possible association between halothane anesthesia and postoperative hepatic necrosis. JAMA 1966; 197:775.
  57. 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.
  58. Moult PJ, Sherlock S. Halothane-related hepatitis. A clinical study of twenty-six cases. Q J Med 1975; 44:99.
  59. Habibollahi P, Mahboobi N, Esmaeili S, et al. Halothane-induced hepatitis: A forgotten issue in developing countries: Halothane-induced hepatitis. Hepat Mon 2011; 11:3.
  60. Voigt MD, Workman B, Lombard C, Kirsch RE. Halothane hepatitis in a South African population--frequency and the influence of gender and ethnicity. S Afr Med J 1997; 87:882.
  61. Cousins MJ, Plummer JL, Hall PD. Risk factors for halothane hepatitis. Aust N Z J Surg 1989; 59:5.
  62. 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.
  63. Dugan CM, MacDonald AE, Roth RA, Ganey PE. A mouse model of severe halothane hepatitis based on human risk factors. J Pharmacol Exp Ther 2010; 333:364.
  64. Fleifel WAN. Effects of halothane anesthesia on patients with abnormal liver function tests. J Basrah Res ((Sciences)) 2011; 4:84.
  65. Neuberger JM. Halothane and hepatitis. Incidence, predisposing factors and exposure guidelines. Drug Saf 1990; 5:28.
  66. Holt C, Csete M, Martin P. Hepatotoxicity of anesthetics and other central nervous system drugs. Gastroenterol Clin North Am 1995; 24:853.
  67. Beaune P, Pessayre D, Dansette P, et al. Autoantibodies against cytochromes P450: role in human diseases. Adv Pharmacol 1994; 30:199.
  68. Kenna JG, Neuberger JM. Immunopathogenesis and treatment of halothane hepatitis. Clin Immunother 1995; 3:108.
  69. Spracklin DK, Thummel KE, Kharasch ED. Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4. Drug Metab Dispos 1996; 24:976.
  70. Sipes IG, Gandolfi AJ, Pohl LR, et al. Comparison of the biotransformation and hepatotoxicity of halothane and deuterated halothane. J Pharmacol Exp Ther 1980; 214:716.
  71. 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.
  72. Njoku D, Laster MJ, Gong DH, et al. Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury. Anesth Analg 1997; 84:173.
  73. Masubuchi Y, Horie T. Toxicological significance of mechanism-based inactivation of cytochrome p450 enzymes by drugs. Crit Rev Toxicol 2007; 37:389.
  74. Minoda Y, Kharasch ED. Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6). Anesthesiology 2001; 95:509.
  75. Carpenter RL, Eger EI 2nd, Johnson BH, et al. The extent of metabolism of inhaled anesthetics in humans. Anesthesiology 1986; 65:201.
  76. Rehder K, Forbes J, Alter H, et al. Halothane biotransformation in man: a quantitative study. Anesthesiology 1967; 28:711.
  77. Kenna JG, Jones RM. The organ toxicity of inhaled anesthetics. Anesth Analg 1995; 81:S51.
  78. Spracklin DK, Hankins DC, Fisher JM, et al. Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J Pharmacol Exp Ther 1997; 281:400.
  79. de Groot H, Noll T. Halothane hepatotoxicity: relation between metabolic activation, hypoxia, covalent binding, lipid peroxidation and liver cell damage. Hepatology 1983; 3:601.
  80. Reichle FM, Conzen PF. Halogenated inhalational anaesthetics. Best Pract Res Clin Anaesthesiol 2003; 17:29.
  81. Gelman S, Dillard E, Bradley EL Jr. Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl. Anesth Analg 1987; 66:936.
  82. Gelman S. General anesthesia and hepatic circulation. Can J Physiol Pharmacol 1987; 65:1762.
  83. Cousins MJ, Sharp JH, Gourlay GK, et al. Hepatotoxicity and halothane metabolism in an animal model with application for human toxicity. Anaesth Intensive Care 1979; 7:9.
  84. Cowan RE, Jackson BT, Grainger SL, Thompson RP. Effects of anesthetic agents and abdominal surgery on liver blood flow. Hepatology 1991; 14:1161.
  85. Manno M, Ferrara R, Cazzaro S, et al. Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro. Pharmacol Toxicol 1992; 70:13.
  86. Baker MT, Vasquez MT, Chiang CK. Evidence for the stability and cytochrome P450 specificity of the phenobarbital-induced reductive halothane-cytochrome P450 complex formed in rat hepatic microsomes. Biochem Pharmacol 1991; 41:1691.
  87. Awad JA, Horn JL, Roberts LJ 2nd, Franks JJ. Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprostanes. Anesthesiology 1996; 84:910.
  88. Plummer JL, Beckwith AL, Bastin FN, et al. Free radical formation in vivo and hepatotoxicity due to anesthesia with halothane. Anesthesiology 1982; 57:160.
  89. Zimmerman HJ. Drug-induced liver disease. In: Schiff's diseases of the liver, Schiff E, Sorrell M, Maddrey WC (Eds), Lippincott-Raven, Philadelphia 1999. p.973.
  90. Krieter PA, van Dyke RA. Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro. Chem Biol Interact 1983; 44:219.
  91. Bourdi M, Amouzadeh HR, Rushmore TH, et al. Halothane-induced liver injury in outbred guinea pigs: role of trifluoroacetylated protein adducts in animal susceptibility. Chem Res Toxicol 2001; 14:362.
  92. Royston D. Free radicals. Formation, function and potential relevance in anaesthesia. Anaesthesia 1988; 43:315.
  93. Pohl LR, Satoh H, Christ DD, Kenna JG. The immunologic and metabolic basis of drug hypersensitivities. Annu Rev Pharmacol Toxicol 1988; 28:367.
  94. Pessayre D, Larrey D. Acute and chronic drug-induced hepatitis. Baillieres Clin Gastroenterol 1988; 2:385.
  95. Neuberger J, Williams R. Halothane anaesthesia and liver damage. Br Med J (Clin Res Ed) 1984; 289:1136.
  96. 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.
  97. Satoh H, Fukuda Y, Anderson DK, et al. Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical evidence of trifluoroacetylated hepatocytes. J Pharmacol Exp Ther 1985; 233:857.
  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.
  99. 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.
  100. 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.
  101. 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.
  102. Beaune PH, Lecoeur S. Immunotoxicology of the liver: adverse reactions to drugs. J Hepatol 1997; 26 Suppl 2:37.
  103. Dansette PM, Bonierbale E, Minoletti C, et al. Drug-induced immunotoxicity. Eur J Drug Metab Pharmacokinet 1998; 23:443.
  104. Anderson JS, Rose NR, Martin JL, et al. Desflurane hepatitis associated with hapten and autoantigen-specific IgG4 antibodies. Anesth Analg 2007; 104:1452.
  105. Njoku DB. Drug-induced hepatotoxicity: metabolic, genetic and immunological basis. Int J Mol Sci 2014; 15:6990.
  106. Eger EI 2nd, Koblin DD, Bowland T, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997; 84:160.
  107. 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.
  108. Mieli-Vergani G, Vergani D, Tredger JM, et al. Lymphocyte cytotoxicity to halothane altered hepatocytes in patients with severe hepatic necrosis following halothane anaesthesia. J Clin Lab Immunol 1980; 4:49.
  109. Kenna JG, Scatchard K, Van Pelt FN, et al. Antibodies to halothane-induced liver antigens in sera from patients with halothane hepatitis: Evidence for a conformation-dependent antigen. Br J Clin Pharmacol 1992; 34:154.
  110. Chen M, Gandolfi J. Characterization of the humoral immune response and hepatotoxicity after multiple halothane exposures in guinea pigs. Drug Metab Rev 1997; 29:103.
  111. Pohl LR, Kenna JG, Satoh H, et al. Neoantigens associated with halothane hepatitis. Drug Metab Rev 1989; 20:203.
  112. Eliasson E, Kenna JG. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol Pharmacol 1996; 50:573.
  113. Satoh H, Gillette JR, Davies HW, et al. Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats. Mol Pharmacol 1985; 28:468.
  114. Hoft RH, Bunker JP, Goodman HI, Gregory PB. Halothane hepatitis in three pairs of closely related women. N Engl J Med 1981; 304:1023.
  115. 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.
  116. 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.
  117. Gut J, Christen U, Huwyler J. Mechanisms of halothane toxicity: novel insights. Pharmacol Ther 1993; 58:133.
  118. Gut J, Christen U, Huwyler J, et al. 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.
  119. Christen U, Jenö P, Gut J. Halothane metabolism: the dihydrolipoamide acetyltransferase subunit of the pyruvate dehydrogenase complex molecularly mimics trifluoroacetyl-protein adducts. Biochemistry 1993; 32:1492.
  120. Heijink E, De Matteis F, Gibbs AH, et al. Metabolic activation of halothane to neoantigens in C57Bl/10 mice: immunochemical studies. Eur J Pharmacol 1993; 248:15.
  121. Christen U, Bürgin M, Gut J. Halothane metabolism: Kupffer cells carry and partially process trifluoroacetylated protein adducts. Biochem Biophys Res Commun 1991; 175:256.
  122. Huwyler J, Gut J. Exposure to the chlorofluorocarbon substitute 2,2-dichloro-1,1,1- trifluoroethane and the anesthetic agent halothane is associated with transient protein adduct formation in the heart. Biochem Biophys Res Commun 1992; 184:1344.
  123. Hastings KL, Thomas C, Hubbard AK, Gandolfi AJ. Screening for antibodies associated with halothane hepatitis. Br J Anaesth 1991; 67:722.
  124. Huwyler J, Aeschlimann D, Christen U, Gut J. The kidney as a novel target tissue for protein adduct formation associated with metabolism of halothane and the candidate chlorofluorocarbon replacement 2,2-dichloro-1,1,1-trifluoroethane. Eur J Biochem 1992; 207:229.
  125. 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.
  126. Farrell G, Prendergast D, Murray M. Halothane hepatitis. Detection of a constitutional susceptibility factor. N Engl J Med 1985; 313:1310.
  127. You Q, Cheng L, Reilly TP, et al. Role of neutrophils in a mouse model of halothane-induced liver injury. Hepatology 2006; 44:1421.
  128. Otsuka S, Yamamoto M, Kasuya S, et al. HLA antigens in patients with unexplained hepatitis following halothane anesthesia. Acta Anaesthesiol Scand 1985; 29:497.
  130. Moore DH, Benson GD. Prolonged halothane hepatitis. Prompt resolution of severe lesion with corticosteroid therapy. Dig Dis Sci 1986; 31:1269.
  131. Windsor JA, Wynne-Jones G. Halothane hepatitis and prompt resolution with methionine therapy: case report. N Z Med J 1988; 101:502.
  132. Elliott RH, Strunin L. Hepatotoxicity of volatile anaesthetics. Br J Anaesth 1993; 70:339.