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Acute and Chronic Liver Diseases Induced by Drugs or Xenobiotics

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Book cover Liver Immunology

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Abstract

The incidence of adverse drug reactions to any given drug may be relatively low, but the total clinical impact of adverse drug reactions is actually substantial because of the number of drugs used and the number of patients treated. It has been estimated that around 7% of patients experience serious adverse drug reactions and that adverse drug reactions are the 4th to 6th leading cause of death (1). Hundreds of drugs and chemicals have been associated with hepatotoxic effects (1–5), and drugs are the most common cause of acute liver failure in the United States and Europe (6,7). In addition, serious druginduced hepatotoxicity has become one of the most frequent causes of postmarketing withdrawal, labeling changes, and restriction in use of medications (Table 1) (8–10).

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References

  1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279:1200–1205.

    Article  PubMed  CAS  Google Scholar 

  2. Lewis JH. Drug-induced liver disease. Med Clin North Am 2000; 84:1275–1311.

    Article  PubMed  CAS  Google Scholar 

  3. Larrey D. Drug-induced liver diseases. J Hepatol 2000; 32(1 Suppl): 77–88.

    Article  PubMed  CAS  Google Scholar 

  4. Kaplowitz N. Avoiding hepatic injury from drugs. Gastroenterology 1999; 117:759.

    Article  PubMed  CAS  Google Scholar 

  5. Lewis JH, Zimmerman HJ. Drugand chemical-induced cholestasis. Clin Liver Dis 1999; 3:433–464.

    Article  PubMed  CAS  Google Scholar 

  6. Williams R. Classification, etiology, and considerations of outcome in acute liver failure. Semin Liver Dis 1996; 16:343–348.

    PubMed  CAS  Google Scholar 

  7. Ostapowicz G, Lee WM. Acute hepatic failure: a Western perspective. J Gastroenterol Hepatol 2000; 15:480–488.

    Article  PubMed  CAS  Google Scholar 

  8. Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 2005; 4:489–499.

    Article  PubMed  CAS  Google Scholar 

  9. Walgren JL, Mitchell MD, Thompson DC. Role of metabolism in drug-induced idiosyncratic hepatotoxicity. Crit Rev Toxicol 2005; 35:325–361.

    Article  PubMed  CAS  Google Scholar 

  10. Bjornsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis 2006; 38:33–38.

    Article  PubMed  CAS  Google Scholar 

  11. Park BK, Naisbitt DJ, Gordon SF, Kitteringham NR, Pirmohamed M. Metabolic activation in drug allergies. Toxicology 2001; 158: 11–23.

    Article  PubMed  CAS  Google Scholar 

  12. Park BK, Kitteringham NR, Powell H, Pirmohamed M. Advances in molecular toxicology-towards understanding idiosyncratic drug toxicity. Toxicology 2000; 153:39–60.

    Article  PubMed  CAS  Google Scholar 

  13. Bissell DM, Gores GJ, Laskin DL, Hoofnagle JH. Drug-induced liver injury: mechanisms and test systems. Hepatology 2001; 33: 1009–1013.

    Article  PubMed  CAS  Google Scholar 

  14. Dansette PM, Bonierbale E, Minoletti C, Beaune PH, Pessayre D, Mansuy D. Drug-induced immunotoxicity. Eur J Drug Metab Pharmacokinet 1998; 23:443–451.

    Article  PubMed  CAS  Google Scholar 

  15. Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK. Adverse drug reactions. BMJ 1998; 316:1295–1298.

    PubMed  CAS  Google Scholar 

  16. Van Pelt FN, Straub P, Manns MP. Molecular basis of drug-induced immunological liver injury. Semin Liver Dis 1995; 15:283–300.

    PubMed  Google Scholar 

  17. Pirmohamed M, Madden S, Park BK. Idiosyncratic drug reactions. Metabolic bioactivation as a pathogenic mechanism. Clin Pharmacokinet 1996; 31:215–230.

    PubMed  CAS  Google Scholar 

  18. Park BK, Pirmohamed M, Kitteringham NR. Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective. Chem Res Toxicol 1998; 11:969–988.

    Article  PubMed  CAS  Google Scholar 

  19. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol Sci 2002; 65:166–176.

    Article  PubMed  CAS  Google Scholar 

  20. Pessayre D, Mansouri A, Haouzi D, Fromenty B. Hepatotoxicity due to mitochondrial dysfunction. Cell Biol Toxicol 1999; 15: 367–373.

    Article  PubMed  CAS  Google Scholar 

  21. Pessayre D, Haouzi D, Fau D, Robin MA, Mansouri A, Berson A. Withdrawal of life support, altruistic suicide, fratricidal killing and euthanasia by lymphocytes: different forms of drug-induced hepatic apoptosis. J Hepatol 1999; 31:760–770.

    Article  PubMed  CAS  Google Scholar 

  22. Ganey PE, Luyendyk JP, Maddox JF, Roth RA. Adverse hepatic drug reactions: inflammatory episodes as consequence and contributor. Chem Biol Interact 2004; 150:35–51.

    Article  PubMed  CAS  Google Scholar 

  23. Beaune PH, Lecoeur S. Immunotoxicology of the liver: adverse reactions to drugs. J Hepatol 1997; 26(Suppl 2):37–42.

    Article  PubMed  CAS  Google Scholar 

  24. Pohl LR, Pumford NR, Martin JL. Mechanisms, chemical structures and drug metabolism. Eur J Haematol Suppl 1996; 60:98–104.

    PubMed  CAS  Google Scholar 

  25. Zimmerman HJ. Drug-induced liver disease. Clin Liver Dis 2000; 4:73–96.

    Article  PubMed  CAS  Google Scholar 

  26. Pumford NR, Halmes NC. Protein targets of xenobiotic reactive intermediates. Annu Rev Pharmacol Toxicol 1997; 37:91–117.

    Article  PubMed  CAS  Google Scholar 

  27. Hasler JA, Estabrook R, Murray M, et al. Human cytochromes P450. Mol Aspects Med 1999; 20:1–137.

    Article  CAS  Google Scholar 

  28. Wilkinson GR. Cytochrome P4503A (CYP3A) metabolism: prediction of in vivo activity in humans. J Pharmacokinet Biopharm 1996; 24:475–490.

    Article  PubMed  CAS  Google Scholar 

  29. Park BK, Pirmohamed M. Toxicogenetics in drug development. Toxicol Lett 2001; 120:281–291.

    Article  PubMed  CAS  Google Scholar 

  30. Pirmohamed M, Park BK. Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci 2001; 22:298–305.

    Article  PubMed  CAS  Google Scholar 

  31. Uetrecht JP. New concepts in immunology relevant to idiosyncratic drug reactions: the “danger hypothesis” and innate immune system. Chem Res Toxicol 1999; 12:387–395.

    Article  PubMed  CAS  Google Scholar 

  32. Naisbitt DJ, Gordon SF, Pirmohamed M, Park BK. Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment. Drug Saf 2000; 23:483–507.

    Article  PubMed  CAS  Google Scholar 

  33. Matzinger P. Introduction to the series. Danger model of immunity. Scand J Immunol 2001; 54:2–3.

    Article  PubMed  CAS  Google Scholar 

  34. Pirmohamed M, Naisbitt DJ, Gordon F, Park BK. The danger hypothesis—potential role in idiosyncratic drug reactions. Toxicology 2002; 181–182:55–63.

    Article  PubMed  Google Scholar 

  35. Park BK, Tingle MD, Grabowski PS, Coleman JW, Kitteringham NR. Drug-protein conjugates—XI. Disposition and immunogenicity of dinitrofluorobenzene, a model compound for the investigation of drugs as haptens. Biochem Pharmacol 1987; 36:591–599.

    Article  PubMed  CAS  Google Scholar 

  36. Cavani A, Ottaviani C, Nasorri F, Sebastiani S, Girolomoni G. Immunoregulation of hapten and drug induced immune reactions. Curr Opin Allergy Clin Immunol 2003; 3:243–247.

    Article  PubMed  CAS  Google Scholar 

  37. June CH, Blazar BR. Clinical application of expanded CD4(+)25(+) cells. Semin Immunol 2006; 18:78–88.

    Article  PubMed  CAS  Google Scholar 

  38. Bluestone JA, Boehmer H. Regulatory T cells. Semin Immunol 2006; 18:77.

    Article  PubMed  Google Scholar 

  39. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3:253–257.

    Article  PubMed  CAS  Google Scholar 

  40. Battaglia M, Gregori S, Bacchetta R, Roncarolo MG. Tr1 cells: from discovery to their clinical application. Semin Immunol 2006; 18:120–127.

    Article  PubMed  CAS  Google Scholar 

  41. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005; 6:345–352.

    Article  PubMed  CAS  Google Scholar 

  42. Kronenberg M, Rudensky A. Regulation of immunity by self-reactive T cells. Nature 2005; 435:598–604.

    Article  PubMed  CAS  Google Scholar 

  43. O’Garra A, Vieira P. Regulatory T cells and mechanisms of immune system control. Nat Med 2004; 10:801–805.

    Article  PubMed  CAS  Google Scholar 

  44. Hoffmann P, Edinger M. CD4+CD25+ regulatory T cells and graftversus-host disease. Semin Hematol 2006; 43:62–69.

    Article  PubMed  CAS  Google Scholar 

  45. Piccirillo CA, Shevach EM. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 2004; 16:81–88.

    Article  PubMed  CAS  Google Scholar 

  46. Samsom JN, van Berkel LA, van Helvoort JM, et al. Fc gamma RIIB regulates nasal and oral tolerance: a role for dendritic cells. J Immunol 2005; 174:5279–5287.

    PubMed  CAS  Google Scholar 

  47. Tridandapani S, Siefker K, Teillaud JL, Carter JE, Wewers MD, Anderson CL. Regulated expression and inhibitory function of Fcgamma RIIb in human monocytic cells. J Biol Chem 2002; 277:5082–5089.

    Article  PubMed  CAS  Google Scholar 

  48. Billadeau DD, Leibson PJ. ITAMs versus ITIMs: striking a balance during cell regulation. J Clin Invest 2002; 109:161–168.

    Article  PubMed  CAS  Google Scholar 

  49. Rao VK, Burris DE, Gruel SM, Sollinger HW, Burlingham WJ. Evidence that donor spleen cells administered through the portal vein prolong the survival of cardiac allografts in rats. Transplantation 1988;45:1145–1146.

    Article  PubMed  CAS  Google Scholar 

  50. Battaglia M, Gianfrani C, Gregori S, Roncarolo MG. IL-10-producing T regulatory type 1 cells and oral tolerance. Ann N Y Acad Sci 2004; 1029:142–153.

    Article  PubMed  CAS  Google Scholar 

  51. Bommireddy R, Doetschman T. TGF-beta, T-cell tolerance and anti-CD3 therapy. Trends Mol Med 2004; 10:3–9.

    Article  PubMed  CAS  Google Scholar 

  52. Graca L, Chen TC, Le Moine A, Cobbold SP, Howie D, Waldmann H. Dominant tolerance: activation thresholds for peripheral generation of regulatory T cells. Trends Immunol 2005; 26:130–135.

    Article  PubMed  CAS  Google Scholar 

  53. Bluestone JA, St Clair EW, Turka LA. CTLA4Ig: bridging the basic immunology with clinical application. Immunity 2006; 24: 233–238.

    Article  PubMed  CAS  Google Scholar 

  54. Kriegel MA, Li MO, Sanjabi S, Wan YY, Flavell RA. Transforming growth factor-beta: recent advances on its role in immune tolerance. Curr Rheumatol Rep 2006; 8:138–144.

    Article  PubMed  CAS  Google Scholar 

  55. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19:683–765.

    Article  PubMed  CAS  Google Scholar 

  56. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998; 16:137–161.

    Article  PubMed  CAS  Google Scholar 

  57. Bresnihan B. Pathogenesis of joint damage in rheumatoid arthritis. J Rheumatol 1999; 26:717–719.

    PubMed  CAS  Google Scholar 

  58. Toussirot E, Wendling D. The use of TNF-alpha blocking agents in rheumatoid arthritis: an overview. Expert Opin Pharmacother 2004; 5:581–594.

    Article  PubMed  CAS  Google Scholar 

  59. Draeger H, Wu X, Roelofs-Haarhuis K, Gleichmann E. Nickel allergy versus nickel tolerance: can oral uptake of nickel protect from sensitization? J Environ Monit 2004; 6:146N–150N.

    PubMed  CAS  Google Scholar 

  60. Cavani A. Breaking tolerance to nickel. Toxicology 2005; 209: 119–121.

    Article  PubMed  CAS  Google Scholar 

  61. Uetrecht J. Role of animal models in the study of drug-induced hypersensitivity reactions. AAPS J 2005; 7:E914–E921.

    Article  CAS  Google Scholar 

  62. Layland LE, Wulferink M, Dierkes S, Gleichmann E. Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25-T cells, prevention by primed CD4+CD25+ T cells. Eur J Immunol 2004; 34:36–46.

    Article  PubMed  CAS  Google Scholar 

  63. Masson MJ, Uetrecht JP. Tolerance induced by low dose D-penicillamine in the brown Norway rat model of drug-induced autoimmunity is immune-mediated. Chem Res Toxicol 2004; 17:82–94.

    Article  PubMed  CAS  Google Scholar 

  64. Gutting BW, Bouzahzah F, Kong PL, Updyke LW, Amacher DE, Craft J. Oxazolone and diclofenac-induced popliteal lymph node assay reactions are attenuated in mice orally pretreated with the respective compound: potential role for the induction of regulatory mechanisms following enteric administration. Toxicol Appl Pharmacol 2003; 189:120–133.

    Article  PubMed  CAS  Google Scholar 

  65. Nierkens S, Aalbers M, Bol M, van Wijk F, Hassing I, Pieters R. Development of an oral exposure mouse model to predict drug-induced hypersensitivity reactions by using reporter antigens. Toxicol Sci 2005; 83:273–281.

    Article  PubMed  CAS  Google Scholar 

  66. Aithal GP, Ramsay L, Daly AK, et al. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology 2004; 39:1430–1440.

    Article  PubMed  CAS  Google Scholar 

  67. Carey JB, Carey MA, Allshire A, van Pelt FN. Tipping the balance towards tolerance: the basis for therapeutic immune modulation by gold? Autoimmunity 2005; 38:393–397.

    Article  PubMed  CAS  Google Scholar 

  68. Adorini L, Giarratana N, Penna G. Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol 2004; 16:127–134.

    Article  PubMed  CAS  Google Scholar 

  69. Calne RY, Sells RA, Pena JR, et al. Induction of immunological tolerance by porcine liver allografts. Nature 1969; 223:472–476.

    Article  PubMed  CAS  Google Scholar 

  70. Chang KM. Regulatory T cells and the liver: a new piece of the puzzle. Hepatology 2005; 41:700–702.

    Article  PubMed  CAS  Google Scholar 

  71. Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol 2003; 3:51–62.

    Article  PubMed  CAS  Google Scholar 

  72. Laloux V, Beaudoin L, Jeske D, Carnaud C, Lehuen A. NK T cellinduced protection against diabetes in V alpha 14-J alpha 281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen. J Immunol 2001; 166:3749–3756.

    PubMed  CAS  Google Scholar 

  73. Mars LT, Laloux V, Goude K, et al. Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice. J Immunol 2002; 168:6007–6011.

    PubMed  CAS  Google Scholar 

  74. Kuniyasu Y, Marfani SM, Inayat IB, Sheikh SZ, Mehal WZ. Kupffer cells required for high affinity peptide-induced deletion, not retention, of activated CD8+ T cells by mouse liver. Hepatology 2004; 39:1017–1027.

    Article  PubMed  Google Scholar 

  75. Lau AH, Thomson AW. Dendritic cells and immune regulation in the liver. Gut 2003; 52:307–314.

    Article  PubMed  CAS  Google Scholar 

  76. O’Connell PJ, Morelli AE, Logar AJ, Thomson AW. Phenotypic and functional characterization of mouse hepatic CD8 alpha+ lymphoidrelated dendritic cells. J Immunol 2000; 165:795–803.

    PubMed  CAS  Google Scholar 

  77. De Creus A, Abe M, Lau AH, Hackstein H, Raimondi G, Thomson AW. Low TLR4 expression by liver dendritic cells correlates with reduced capacity to activate allogeneic T cells in response to endotoxin. J Immunol 2005; 174:2037–2045.

    PubMed  Google Scholar 

  78. Knolle P, Schlaak J, Uhrig A, Kempf P, Meyer zum Buschenfelde KH, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol 1995; 22:226–229.

    Article  PubMed  CAS  Google Scholar 

  79. Uhrig A, Banafsche R, Kremer M, et al. Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver. J Leukoc Biol 2005; 77:626–633.

    Article  PubMed  CAS  Google Scholar 

  80. Calkins CM, Bensard DD, Shames BD, et al. IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia. J Endotoxin Res 2002; 8:59–67.

    PubMed  CAS  Google Scholar 

  81. Ju C, McCoy JP, Chung CJ, Graf ML, Pohl LR. Tolerogenic role of Kupffer cells in allergic reactions. Chem Res Toxicol 2003; 16: 1514–1519.

    Article  PubMed  CAS  Google Scholar 

  82. Ju C, Pohl LR. Tolerogenic role of Kupffer cells in immune-mediated adverse drug reactions. Toxicology 2005; 209:109–112.

    Article  PubMed  CAS  Google Scholar 

  83. Knolle PA. Involvement of the liver in the induction of CD8 T cell tolerance towards oral antigen. Z Gastroenterol 2006; 44: 51–56.

    Article  PubMed  CAS  Google Scholar 

  84. Safadi R, Alvarez CE, Ohta M, et al. Enhanced oral tolerance in transgenic mice with hepatocyte secretion of IL-10. J Immunol 2005; 175:3577–3583.

    PubMed  CAS  Google Scholar 

  85. Beutler B. Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol 2000; 12(1):20–26.

    Article  PubMed  CAS  Google Scholar 

  86. Eipel C, Bordel R, Nickels RM, Menger MD, Vollmar B. Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat model of systemic endotoxemia. Am J Physiol Gastrointest Liver Physiol 2004; 286:G769–G776.

    Article  PubMed  CAS  Google Scholar 

  87. Arbour NC, Lorenz E, Schutte BC, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000; 25:187–191.

    Article  PubMed  CAS  Google Scholar 

  88. Stoclet JC, Muller B, Andriantsitohaina R, Kleschyov A. Overproduction of nitric oxide in pathophysiology of blood vessels. Biochemistry (Mosc) 1998; 63:826–832.

    CAS  Google Scholar 

  89. Saetre SS, Andersen NJ, Houe T, et al. Regulation of porcine biliary secretion by secretin. Acta Physiol Scand 1998; 163:113–119.

    Article  PubMed  CAS  Google Scholar 

  90. Rockey DC, Chung JJ. Regulation of inducible nitric oxide synthase in hepatic sinusoidal endothelial cells. Am J Physiol 1996; 271: G260–G267.

    PubMed  CAS  Google Scholar 

  91. Kamanaka Y, Kawabata A, Matsuya H, Taga C, Sekiguchi F, Kawao N. Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat. Life Sci 2003; 74:793–802.

    Article  PubMed  CAS  Google Scholar 

  92. Fiorucci S, Antonelli E, Distrutti E, et al. Liver delivery of NO by NCX-1000 protects against acute liver failure and mitochondrial dysfunction induced by APAP in mice. Br J Pharmacol 2004; 143: 33–42.

    Article  PubMed  CAS  Google Scholar 

  93. Nanji AA, Griniuviene B, Yacoub LK, Fogt F, Tahan SR. Intercellular adhesion molecule-1 expression in experimental alcoholic liver disease: relationship to endotoxemia and TNF alpha messenger RNA. Exp Mol Pathol 1995; 62:42–51.

    Article  PubMed  CAS  Google Scholar 

  94. Thurman RG. II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol 1998; 275:G605–G611.

    PubMed  CAS  Google Scholar 

  95. Rao RK, Seth A, Sheth P. Recent Advances in Alcoholic Liver Disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 2004; 286:G881–G884.

    Article  PubMed  CAS  Google Scholar 

  96. Hines IN, Wheeler MD. Recent advances in alcoholic liver disease III. Role of the innate immune response in alcoholic hepatitis. Am J Physiol Gastrointest Liver Physiol 2004; 287:G310–G314.

    Article  PubMed  CAS  Google Scholar 

  97. Wheeler MD, Kono H, Yin M, et al. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Free Radic Biol Med 2001; 31:1544–1549.

    Article  PubMed  CAS  Google Scholar 

  98. Bird GL, Sheron N, Goka AK, Alexander GJ, Williams RS. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med 1990; 112:917–920.

    PubMed  CAS  Google Scholar 

  99. Felver ME, Mezey E, McGuire M, et al. Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin Exp Res 1990; 14:255–259.

    Article  PubMed  CAS  Google Scholar 

  100. McClain CJ, Cohen DA, Dinarello CA, Cannon JG, Shedlofsky SI, Kaplan AM. Serum interleukin-1 (IL-1) activity in alcoholic hepatitis. Life Sci 1986; 39:1479–1485.

    Article  PubMed  CAS  Google Scholar 

  101. Hill DB, Marsano L, Cohen D, Allen J, Shedlofsky S, McClain CJ. Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med 1992; 119:547–552.

    PubMed  CAS  Google Scholar 

  102. Sheron N, Bird G, Koskinas J, et al. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration. Hepatology 1993; 18:41–46.

    PubMed  CAS  Google Scholar 

  103. Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG. Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 1995; 108:218–224.

    Article  PubMed  CAS  Google Scholar 

  104. Nanji AA, Khettry U, Sadrzadeh SM. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Proc Soc Exp Biol Med 1994; 205:243–247.

    PubMed  CAS  Google Scholar 

  105. Iimuro Y, Gallucci RM, Luster MI, Kono H, Thurman RG. Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology 1997; 26:1530–1537.

    Article  PubMed  CAS  Google Scholar 

  106. Le Moine O, Marchant A, De Groote D, Azar C, Goldman M, Deviere J. Role of defective monocyte interleukin-10 release in tumor necrosis factor-alpha overproduction in alcoholics cirrhosis. Hepatology 1995; 22:1436–1439.

    Article  PubMed  Google Scholar 

  107. Hill DB, D’Souza NB, Lee EY, Burikhanov R, Deaciuc IV, de Villiers WJ. A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide. Alcohol Clin Exp Res 2002; 26:74–82.

    PubMed  CAS  Google Scholar 

  108. Yee SB, Kinser S, Hill DA, et al. Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline. Toxicol Appl Pharmacol 2000; 166:173–185.

    Article  PubMed  CAS  Google Scholar 

  109. Luyendyk JP, Shores KC, Ganey PE, Roth RA. Bacterial lipopolysaccharide exposure alters aflatoxin B(1) hepatotoxicity: benchmark dose analysis for markers of liver injury. Toxicol Sci 2002; 68:220–225.

    Article  PubMed  CAS  Google Scholar 

  110. Lind RC, Gandolfi AJ, Sipes IG, Brown BR Jr. The involvement of endotoxin in halothane-associated liver injury. Anesthesiology 1984; 61:544–550.

    Article  PubMed  CAS  Google Scholar 

  111. Labib R, Turkall R, Abdel-Rahman MS. Endotoxin potentiates the hepatotoxicity of cocaine in male mice. J Toxicol Environ Health A 2002; 65:977–993.

    Article  PubMed  CAS  Google Scholar 

  112. Buchweitz JP, Ganey PE, Bursian SJ, Roth RA. Underlying endotoxemia augments toxic responses to chlorpromazine: is there a relationship to drug idiosyncrasy? J Pharmacol Exp Ther 2002; 300:460–467.

    Article  PubMed  CAS  Google Scholar 

  113. Fisher AA, Le Couteur DG. Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. Drug Saf 2001; 24:39–57.

    Article  PubMed  CAS  Google Scholar 

  114. Luyendyk JP, Maddox JF, Cosma GN, Ganey PE, Cockerell GL, Roth RA. Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats. J Pharmacol Exp Ther 2003; 307:9–16.

    Article  PubMed  CAS  Google Scholar 

  115. Grove J, Daly AK, Bassendine MF, Gilvarry E, Day CP. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut 2000; 46:540–545.

    Article  PubMed  CAS  Google Scholar 

  116. Louis E, Franchimont D, Piron A, et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 1998; 113:401–406.

    Article  PubMed  CAS  Google Scholar 

  117. Lee WM. Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology 2004; 40:6–9.

    Article  PubMed  CAS  Google Scholar 

  118. Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther 1973; 187:185–194.

    PubMed  CAS  Google Scholar 

  119. Mitchell JR, Jollow DJ, Potter WZ, et al. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. V. Correlation of hepatic necrosis, covalent binding and glutathione depletion in hamsters. IV. Protective role of glutathione. J Pharmacol Exp Ther 1973; 187:185–194.

    PubMed  CAS  Google Scholar 

  120. Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 1973; 187:211–217.

    PubMed  CAS  Google Scholar 

  121. Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. J Pharmacol Exp Ther 1973; 187:195–202.

    PubMed  CAS  Google Scholar 

  122. Jaeschke H, Bajt ML. Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 2006; 89: 31–41.

    Article  PubMed  CAS  Google Scholar 

  123. Gale EA. Lessons from the glitazones: a story of drug development. Lancet 2001; 357:1870–1875.

    Article  PubMed  CAS  Google Scholar 

  124. Smith MT. Mechanisms of troglitazone hepatotoxicity. Chem Res Toxicol 2003; 16:679–687.

    Article  PubMed  CAS  Google Scholar 

  125. Chojkier M. Troglitazone and liver injury: in search of answers. Hepatology 2005; 41:237–246.

    Article  PubMed  CAS  Google Scholar 

  126. Uetrecht J. Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Discov Today 2003; 8: 832–837.

    Article  PubMed  CAS  Google Scholar 

  127. Williams DP, Park BK. Idiosyncratic toxicity: the role of toxicophores and bioactivation. Drug Discov Today 2003; 8:1044–1050.

    Article  PubMed  CAS  Google Scholar 

  128. 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; 1:821–824.

    Article  PubMed  CAS  Google Scholar 

  129. Wright R, Eade OE, Chisholm M, et al. Controlled prospective study of the effect on liver function of multiple exposures to halothane. Lancet 1975; 1:817–820.

    Article  PubMed  CAS  Google Scholar 

  130. Kenna JG. The molecular basis of halothane-induced hepatitis. Biochem Soc Trans 1991; 19:191–195.

    PubMed  CAS  Google Scholar 

  131. Ray DC, Drummond GB. Halothane hepatitis. Br J Anaesth 1991; 67:84–99.

    Article  PubMed  CAS  Google Scholar 

  132. Kenna JG, Neuberger J, Williams R. Specific antibodies to halothaneinduced liver antigens in halothane-associated hepatitis. Br J Anaesth 1987; 59:1286–1290.

    Article  PubMed  CAS  Google Scholar 

  133. 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: 733–740.

    PubMed  CAS  Google Scholar 

  134. 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: 1103–1109.

    PubMed  CAS  Google Scholar 

  135. Knight TL, Scatchard KM, Van Pelt FN, Kenna JG. Sera from patients with halothane hepatitis contain antibodies to halothaneinduced liver antigens which are not detectable by immunoblotting. J Pharmacol Exp Ther 1994; 270:1325–1333.

    PubMed  CAS  Google Scholar 

  136. Kenna JG, Van Pelt F. The metabolism and toxicity of inhaled anaesthetic agents. Anaesth Pharmacol Rev 1994; 2:29–42.

    CAS  Google Scholar 

  137. Kenna JG, Martin JL, Pohl LR. The topography of trifluoroacetylated protein antigens in liver microsomal fractions from halothane treated rats. Biochem Pharmacol 1992; 44:621–629.

    Article  PubMed  CAS  Google Scholar 

  138. Eliasson E, Kenna JG. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol Pharmacol 1996; 50: 573–582.

    PubMed  CAS  Google Scholar 

  139. Kenna JG, Knight TL, van Pelt FN. Immunity to halothane metabolite-modified proteins in halothane hepatitis. Ann N Y Acad Sci 1993; 685:646–661.

    Article  PubMed  CAS  Google Scholar 

  140. 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: 788–793.

    PubMed  CAS  Google Scholar 

  141. Satoh H, Gillette JR, Takemura T, et al. Investigation of the immunological basis of halothane-induced hepatotoxicity. Adv Exp Med Biol 1986; 197:657–673.

    PubMed  CAS  Google Scholar 

  142. Bourdi M, Chen W, Peter RM, et al. Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem Res Toxicol 1996; 9:1159–1166.

    Article  PubMed  CAS  Google Scholar 

  143. Spracklin DK, Hankins DC, Fisher JM, Thummel KE, Kharasch ED. Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J Pharmacol Exp Ther 1997; 281: 400–411.

    PubMed  CAS  Google Scholar 

  144. 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; 116:123–141.

    Article  PubMed  CAS  Google Scholar 

  145. 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; 18:858–863.

    Article  PubMed  CAS  Google Scholar 

  146. Smith GC, Kenna JG, Harrison DJ, Tew D, Wolf CR. Autoantibodies to hepatic microsomal carboxylesterase in halothane hepatitis. Lancet 1993; 342:963–964.

    Article  PubMed  CAS  Google Scholar 

  147. 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; 8:1635–1641.

    Article  PubMed  CAS  Google Scholar 

  148. Kitteringham NR, Kenna JG, Park BK. Detection of autoantibodies directed against human hepatic endoplasmic reticulum in sera from patients with halothane-associated hepatitis. Br J Clin Pharmacol 1995; 40:379–386.

    PubMed  CAS  Google Scholar 

  149. Beaune P, Dansette PM, Mansuy D, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a druginduced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sci USA 1987; 84:551–555.

    Article  PubMed  CAS  Google Scholar 

  150. 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.

    Article  PubMed  CAS  Google Scholar 

  151. Mieli-Vergani G, Vergani D, Tredger JM, Eddleston AL, Davis M, Williams R. Lymphocyte cytotoxicity to halothane altered hepatocytes in patients with severe hepatic necrosis following halothane anaesthesia. J Clin Lab Immunol1980; 4:49–51.

    PubMed  CAS  Google Scholar 

  152. Neuberger JM, Kenna JG, Williams R. Halothane hepatitis: attempt to develop an animal model. Int J Immunopharmacol 1987; 9:123–131.

    Article  PubMed  CAS  Google Scholar 

  153. Pohl LR, Kenna JG, Satoh H, Christ D, Martin JL. Neoantigens associated with halothane hepatitis. Drug Metab Rev 1989; 20:203–217.

    Article  PubMed  CAS  Google Scholar 

  154. Neve EP, Ingelman-Sundberg M. Molecular basis for the transport of cytochrome P450 2E1 to the plasma membrane. J Biol Chem 2000; 275:17,130–17,135.

    Article  PubMed  CAS  Google Scholar 

  155. Aithal GP, Rawlins MD, Day CP. Accuracy of hepatic adverse drug reaction reporting in one English health region. Bmj 1999; 319:1541.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland

    Frank N. A. M. van Pelt MSC, PhD

  2. Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC

    Michelle A. Carey PhD

  3. Department of Immunology, The Scripps Research, Institute, La Jolla, CA

    John B. Carey PhD (Research Fellow)

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  1. Frank N. A. M. van Pelt MSC, PhD
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  2. Michelle A. Carey PhD
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  3. John B. Carey PhD
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Editors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA

    M. Eric Gershwin MD, FACP

  2. Departments of Medicine and Surgery Baylor Liver Health, Baylor College of Medicine, Houston, TX

    John M. Vierling MD, FACP

  3. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Hannover, Germany

    Michael P. Manns MD

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van Pelt, F.N.A.M., Carey, M.A., Carey, J.B. (2007). Acute and Chronic Liver Diseases Induced by Drugs or Xenobiotics. In: Gershwin, M.E., Vierling, J.M., Manns, M.P. (eds) Liver Immunology. Humana Press. https://doi.org/10.1007/978-1-59745-518-3_30

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