Mechanisms of liver damage

Seminars in Liver Disease

Volumn 16, Issue 4, 1996, Pages 357-367

  Losser, Marie Reine ^a   Payen, Didier ^b,c  

^a Hop Universitiare Lariboisiere ^*  (France)

^b INSERM   (France)

^c HÔPITAL LARIBOISIÈRE   (France)

Author keywords

acute liver damage; biochemical injury; detoxification; drug cytotoxicity; immunology

Indexed keywords

PARACETAMOL;

ALCOHOL LIVER CIRRHOSIS; DRUG OVERDOSE; GRAFT REJECTION; HUMAN; LIVER FAILURE; LIVER INJURY; LIVER ISCHEMIA; LIVER TOXICITY; LIVER TRANSPLANTATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; SEPSIS; VIRUS HEPATITIS;

EID: 0030452899     PISSN: 02728087     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-1007249     Document Type: Review

References (154)

1. Anders MW: Bioactivation mechanisms and hepatocellular damage. In: Arias IM, Jakoby WB. Popper H, et al. (eds): The liver: Biology and pathobiology. 2nd ed. New York, Raven Press, 1988, pp 389-400.
2. Rosser BG, Gores GJ: Liver cell necrosis: cellular mechanisms and clinical implications. GastroenteroJogy 108:252-75, 1995.
3. DeLeve L, Kaplowitz N: Mechanisms of drug-induced liver disease. In: Lewis J (ed): Drug-induced liver disease. Gastroenterology Clinics of North America. Philadelphia, WB Saunders, 1995, pp 787-810.
4. Trey C, Davidson CS: The management of fulminant hepatic failure. Prog Liver Dis 3:282-98, 1970.
5. Steinberg P., Lafranconi WM, Wolf CR, et al: Xenobiotic metabolizing enzymes are not restricted to parenchymal cells in rat liver. Mol Pharmacol 32:463-70, 1987.
6. Rollins BJ: Hepatic veno-occlusive disease. Am J Med 81:297-306, 1986.
7. Prentki M, Chaponnier C, Jeanrenaud B, Gabbiani G: Actin microfilaments, cell shape, and secretory processes in isolated rat hepatocytes. J Cell Biol 81:592-607, 1979.
8. Wieland T: Modification of actins by phallotoxins. Naturwissenschaften 64:303-9, 1977.
9. Florine-Casteel K, Lemasters JJ, Herman B: Lipid order in hepatocyte plasma membrane blebs during ATP depletion measured by digitized video fluorescence polarization microscopy. FASEB J 5:2078-84, 1991.
10. 2- J Biol Chem 268:1011-16, 1993.
11. + binding sites with opposing effects on the pore open probability. J Biol Chem 268:1005-10, 1993.
12. Cui L, Yoon S, Shinazi RF, Sommadossi J-P: Cellular and molecular events leading to mitochondrial toxiciry of l-(2-deoxy-2-fluoro-l-β-D-arabinofuranosyl)-5-iodouracil in human liver cells. J Clin Invest 95:555-63, 1995.
13. McKenzie R, Fried M, Sallie R, et al: Hepatic failure and lactic acidosis due to fialuridine (FIAU). an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 333:1099-1105, 1995.
14. Bronk SF. Gores GJ: pH dependent, non-lysosomal proteolysis contributes to lethal anoxic cell injury of rat hepatocytes. Am J Physiol 264:G744-51, 1993.
15. Bus JS, Aust S, Gibson JE: Superoxide- and singlet oxygen-catalyzed lipid peroxidation as a possible mechanism for paraquat (methyl viologen) toxicity. Biochem Biophys Res Comm 58:749-55, 1974.
16. Kiotaki C, Peisach J, Bloom BR: Oxygen metabolism in cloned macrophage cell lines: Glucose dependence of Superoxide production, metabolic and spectral analysis. J Immunol 132:857-66, 1984.
17. Spolarics Z, Bagby GJ, Lang CH, Spitzer JJ: Up-regulation of glucose metabolism in Kupffer cells following infusion of tumour necrosis factor. Biochem J 278:515-19, 1991.
18. Tribble DL, Aw TK, Jones DP. The pathophysiological significance of lipid peroxidation in oxidative cell injury. Hepatology 7:377-87, 1987.
19. Minnoti G, Aust SD: The requirement for iron (III) in the initiation of lipid peroxidation by iron (II) and hydrogen peroxide. J Biol Chem 262:1098-1104, 1987.
20. Shimoda R, Nagashima M, Sakamoto M, et al: Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine. in human livers with chronic hepatitis. Cancer Res 54:3171-2, 1994.
21. Jaeschke H: Mechanisms of oxidant stress-induced acute tissue injury. PSEBM 209:104-11, 1995.
22. Nathan C: Nitric oxide as a secretory product of mammalian cells. FASEB J 6:3051-64, 1992.
23. Marietta MA: Nitric oxide synthase structure and mechanism. J Biol Chem 268:12237-4, 1993.
24. Spitzer JA: Cytokine regulation of nitric oxide formation and differential regulation in hepatocytes and non parenchymal cells in endotoxemic rats. Hepatology 19:217-28, 1994.
25. Stamler JS, Jaraki O, Simon DI, et al: Nitric oxide circulates in mammalian plasma primarily as a S-nitroso adduct of serum albumin. Proc Nail Acad Sci USA 89:7674-7, 1992.
26. Stamler JS, Singet DJ, Loscalzo J: Biochemistry of nitric oxide and its redox-activated forms. Science 258:1898-1902, 1992.
27. Clancy RM, Abramson SB: Nitric oxide: A novel mediator of inflammation. PSEBM 209:93-101, 1995.
28. Ignarro LJ, Degnan JN, Baricos WH, et al: Activation of purified guanylate cyclase by nitric oxide requires heme: comparison of heme-deficient. heme-reconstituted, and heme-containing forms of soluble enzyme from bovine lung. Biochem Biophys Acta 718:49-55, 1982.
29. Clancy RM, Leszczynska-Piziak J, Amin A, et al: Nitric oxide ADP-ribosylates actin in association with the inhibition of cytoskeletal assembly neutrophils. J Leukoc Biol 58:196-202, 1995.
30. Bautista AP, Spitzer JJ: Inhibition of nitric oxide formation in vivo enhances Superoxide release by the perfused liver. Am J Physiol 266 (Gastrointest Liver Physiol 29):G783-8, 1994.
31. Bohlinger I, Leist M, Barsig J, et al: lnterleukin-1 and nitric oxide protect against tumor necrosis factor a-induced liver injury through distinct pathways. Hepatology 22:1829-37, 1995.
32. Beckman JS, Beckman TW, Chen J, et al: Apparent hydroxyl radical production by peroxynitrite: Implication for endothelial cell injury from nitric oxide and Superoxide. Proc Natl Acad Sci USA 87:1620-4, 1990.
33. Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of Superoxide and nitric oxide. Arch Biochem Biophys 288-481-7, 1991
34. Ioannidis I, de Groot H: Cytotoxicity of nitric oxide in Fu5 hepatoma cells: evidence for co-operative action with hydrogen peroxide. Biochem J 296:341-5, 1993.
35. Pacelli R, Wink DA, Cook JA, et al: Nitrix oxide potentiates hydrogen peroxide-induced killing of Escherichia coli. J Exp Med 182 1469-79, 1995.
36. Kenna J, Satoh H, Christ D, Pohl L: Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contains the trifhioroacetyl group derived from halothane. J Pharmacol Exp Ther 245:1103-9, 1988.
37. Vergani D, Mieli-Vergani G, Alberti A, el al: Antibodies to the surface of halothane-altered rabbit hepaocytes in patients with severe halothane-associated hepatitis. N Engl J Med 303:66-71, 1980.
38. Kretz-Rommel A, Boelsterli UA: Selective protein adducts to membrane proteins in cultured rat hepatocytes exposed to diclofenac: Radiochemical and immunochemical analysis. Molec Pharmacol 45:237-44, 1993.
39. Kretz-Rommel A, Boelsterli UA: Cytotoxic activity of T cells and non-T cells from diclofenac-immunized mice against cultured syngeneic hepatocytes exposed to diclofenac. Hepatology 22:213-22, 1995.
40. Israel Y, Hurwitz E, Niemela O, Amon R: Monoclonal and polyclonal antibodies acetaldehyde-containing epitopes in acetaldehyde-protein adducts. Proc Natl Acad Sci USA 83:7923-7, 1986.
41. Decker K: Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem 192:245-61, 1990.
42. Olynyk JK, Matuschak GM, Lechner AJ, et al: Differential production of TNF by Kupffer cells after phagocytosis of E. coli and C. albicans. Am J Physiol 267(Gastrointest, Liver Physiol. 30):G213-19, 1994.
43. Tran-Thi T-A, Weinhold L. Weinstock C, et al: Production of tumor necrosis factor-α, interleukin-1 and interleukin-6 in the perfused rat liver. Eur Cytokine Netw 4:363-70, 1993.
44. Wang JH, Redmond HP, Watson RWG, Bouchier-Hayes D: Role of lipopolysaccharide and tumor necrosis factor-a in induction of hepatocyte necrosis. Am J Physiol 269(Gastrointest Liver Physiol):G297-G304, 1995.
45. Mészaros K, Lang CH, Bagby GJ, Spitzer JJ: Tumor necrosis factor increases in vivo glucose utilization of macrophages-rich tissues. Biochem Biophys Res Commun 149:1-6, 1987.
46. Besedovsky HO, del-Rey A: Interleukin-1 and glucose homeostasis: an example of the biological relevance of immune-neuroendocrine interactions. Horm Res 31:94-9, 1989.
47. Memon RA, Feingold KR, Moser AH, et al: Differential effects of interleukin-1 and tumor necrosis factor on ketogenesis. Am J Physiol 263(Endocrinol Metab 26):E301-9, 1992.
48. Whitting J, Green RM, Rosenbluth AB, Gollan JL: Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology 22:1273-78, 1991.
49. Heinrich PC, Castell JV, Andus T: Interieukin-6 and the acute phase response. 265:621-36, 1990.
50. Kopf M, Baumann H, Freer G, et al: Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339-42, 1994.
51. Thornton AJ, Strieter RM, Lindley I, et al: Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. J Immunol 144:2609-13, 1989.
52. Albina JE, Reichner JS: Nitric oxide in inflammation and immunity. New Horizons 3:46-64, 1995.
53. Payen D, Bernard C, Beloucif S: Nitric oxide in sepsis. Clin Chest Med 17:333-50, 1996.
54. Stamler JS: Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 78:931-6, 1994.
55. Liew FY: Regulation of lymphocyte functions by nitric oxide. Curr Opin Immunol 7:396-9, 1995.
56. Jaeschke H, Farhood A, Bautista AP, et al: Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia. Am J Physiol 264:G801-9, 1993.
57. Witthaut R, Farhood A, Smith CW, Jaeschke H: Complement and tumor necrosis factor-α contribute to MAC-1 (CD11b/CD18) up-regulation and systemic neutrophil activation during endotoxemia in vivo. J Leukoc Biol 55:105-11, 1994.
58. 5a. Am J Pathol 135:489-97, 1989.
59. Jaeschke H: Pathophysiology of hepatic ischemia-reperfusion injury: the role of complement activation. Gastroenterology 107:583-6, 1994. Editorial/Comment.
60. Shingu M, Nonaka S, Nishimukai H, et al: Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils. Clin Exp Immunol 90:72-8, 1992.
61. Doi F, Goya T, Torisu M: Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis. Hepatology 17:1086-94, 1993.
62. Tschopp J, Nabholz M: Perforin-mediated target cell lysis by cytolytic lymphocytes. Annu Rev Immunol 8:279-302, 1990.
63. Shulman HM, Gown AM, Nugent DJ: Hepatic veno-occlusive disease after bone marrow transplantation. Am J Pathol 127:549-58, 1987.
64. Shirai M, Nagashima K, Iwasaki S, Mori W: A light and scanning electron microscopic study of hepatic veno-occlusive disease. Acta Pathol Jpn 37:1961-71, 1987.
65. Deleve LD: Dacarbazine toxicky in murine liver cells: a model of hepatic endothelial injury and glutathione defense. J Pharmacol Exp Ther 268:1261-70, 1994.
66. Zimmerman HJ, Lewis JH: Chemical- and toxin-induced hepatotoxicity. In: Lewis J (ed): Drug-induced liver disease. Gastroenterology Clinics of North America. Philadelphia, WB Saunders, 1995, pp 1027-45.
67. McLean EK: The toxic actions of pyrrolizidine (Senicio) alkaloids. Pharmacol Rev 22:429-83, 1970.
68. Pietsch M, Georg M, Tschopp J: The apoptosis endonuclease: cleaning up after cell death. Trends Cell Biol 4:37-41, 1994.
69. Benedetti AA. Jezaquel M, Orlandi F: Preferential distribution of apoptotic bodies in acinar zone 3 of normal human and rat liver. J Hepatol 7:319-24, 1988.
70. Smith CA, Farrah T, Goodwin RG: The TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death. Cell 76:959-62, 1994.
71. Leithauser F, Dhein J, Mechtersheimer G, et al: Constitutive and induced expression of APO-1, a new member of the NGF/TNF receptor superfamily, in normal and neoplastic cells. Lab Invest 69:415-29, 1993.
72. Suda T, Nagata S: Purification and characterization of the Fasligand that induces apoptosis. 1 Exp Med 179:873-9, 1994.
73. Kägi D, Vjgnaux F, Ledermann B. et al: Fas and perform pathways as a major mechanisms of T-cell-mediated cytotoxicity. Science (Wash DC) 265:528-530, 1994.
74. Mita E, Hayashi N, Iio S, et al: Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Bichem Biophys Res Commun 204:468-74, 1994.
75. Galle PR, Hofmann WJ, Walczak H, et al: Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med 182:1123-1230, 1995.
76. Laster SN, Wood JG, Gooding LR: Tumor necrosis factor induces both apoptotic and necrotic form of cell lysis. J Immunol 141:2629-34, 1988.
77. Tracey KJ, Beutler B, Lowry SF, et al: Shock and tissue injury induced by recombinant human cachectin. Science 234:470-4, 1986.
78. Mathison JC, Wolfson E, Ulevitch RJ: Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 81:1925-37, 1988.
79. Beutler BA: Orchestration of septic shock by cytokines: the role of cachectin (tumor necrosis factor). Prog Clin Biol Res 286:219-35, 1989.
80. Gantner F, Leist M, Jilg S. et al: Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice. Gastroenterology 109:166-76, 1995.
81. Leist M, Gantner F, Bohlinger I, et al: Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol 146:1220-34, 1995.
82. Gonzalez-Flecha B, Cutrin JC, Boveris A: Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456-64, 1993.
83. Lehninger AL: Electron transport, oxidative phosphorylation, and regulation of ATP production. In: Lehninger AL (ed): Principles of biochemistry. 4th ed. New York, Worth Publishers, 1988, pp 467-510.
84. 2+. Molecular Physiology 8:515-24, 1985.
85. 2 and dependence of viability of glycolysis. Am J Physiol 257:G58-G64, 1989.
86. Eberli FR, Weinberg EO, Grice WN, et al: Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocytes suspensions. Circ Res 68:466-81, 1991.
87. Sano W, Watanabe F, Tamai H. et al: Beneficial effect of fructose-1,6-bisphosphate on mitochondrial function during ischemia-reperfusion of rat liver. Gastroenterology 108:1785-92, 1995.
88. Bronk SF, Gores GJ: Efflux of protons from acidic vesicles contributes to cytosohc acidification of hepatocytes during ATP depletion. Hepatology 14:626-33, 1991.
89. Gores GJ, Nieminen A-L, Wray BE, et al: Intracellular pH during "chemical hypoxia" in cultured rat hepatocytes: protection by intracellular acidosis against the onset of cell death. J Clin Invest 83:386-96, 1989.
90. 2 contributes to loss of plasma membrane integrity during chemical hypoxia in rat hepatocytes. Biochem Biophys Res Comm 174:654-9, 1991.
91. 2+, and cytotoxicity in rat hepatocytes. J Biol Chem 267:6654-63, 1992.
92. 2+ in cell injury, necrosis and apoptosis. Curr Opin Cell Biol 4:227-32, 1992.
93. Lemasters JJ, Ji S, Thurman RG: Centrilobular injury following hypoxia in isolated, perfused rat liver. Science 213:661-3, 1981.
94. Ikeda T, Yanaga K, Kishikawa K, et al: Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. Hepatology 16:454-61, 1992.
95. Clavien PA, Harvey RC, Strasberg SM: Preservation and reperfusion injuries in liver allografts. Transplantation 53:957-78, 1992.
96. Caldwell-Kenkel JC, Thurman RG, Lemasters JJ: Selective loss of nonparenchymal cell viability after cold ischemic storage of rat livers. Transplantation 45:834-7, 1988.
97. Jaeschke H, Smith CV, Mitchell JR: Reactive oxygen species during ischemia-reflow injury in isolated perfused rat liver. J Clin Invest 81:1240-6, 1988.
98. Connor HD, Gao W, Nukina S, et al: Evidence that free radicals are involved in graft failure following orthotopic liver transplantation in the rat: electron paramagnetic resonance spin trapping study. Transplantation 54:199-204, 1992.
99. Walsh TR, Rao PN, Makowka L, Starlz TE: Lipid peroxidation is a nonparenchymal event with reperfusion after prolonged liver ischemia. J Surg Res 49:18-23, 1990.
100. Mathews WR, Guido DM, Fisher MA, Jaeschke H: Lipid peroxidation as molecular mechanism of liver cell injury during reperfusion after ischemia. Free Radic Biol Med 16:763-70, 1994.
101. Davies KJ: Protein damage and degradation by oxygen radicals. L General aspects. J Biol Chem 262:9895-9, 1987.
102. Scoazec JY, Delautier D, Moreau A, et al: Expression of complement-regulatory proteins in normal and UW-preserved human liver. Gastroemerology 107:505-16, 1994.
103. Brass CA. Nunes F, Nagpal R: Increased oxyradical production during reoxygenation of perfused rat liver. Transplantation 58:1329-35, 1994.
104. Caldwell-Kenkel JC, Currin RT, Tanaka Y, et al: Reperfusion injury to endothelial cells following cold ischemic storage of rat livers. Hepatology 10:292-9, 1989.
105. Bremer C, Bradford BU, Hunt KJ, et al: Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. Am J Physiol 267(Gastrointest Liver Physiol 30):G630-6, 1994.
106. Imamura H, Sutto F, Brault A, Huet P-M: Role of Kupffer cells in cold ischemia/reperfusion injury of rat liver. Gastroenterology 109:189-97, 1995.
107. Brass CA, Roberts TG: Hepatic free radical production after cold storage. Kupffer cell-dependent and -independent mechanisms in rats. Gastroenterology 108:1167-75, 1995.
108. Lefer AM, Lefer DJ: Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 33:71-90, 1993.
109. Lefer AM. Ma XL: Endothelial dysfunction in the splanchnic circulation following ischemia and reperfusion. J Cardiovasc Pharmacol 17(suppl 3):S186-90, 1991.
110. Tsao PS, Aoki N. Lefer DJ, et al: Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat. Circulation 82:1402-12, 1990.
111. Siegfried MR. Erhardt J. Rider T. et al: Cardioprotection and attenuation of endothelial dysfunction by organic nitric oxide donors in myocardial ischemia-reperfusion. J Pharmacol Exp Therap 260:668-75, 1992.
112. Cristol JP, Thiemermann C, Mitchell JA, et al: Support of renal blood flow after ischaemic-reperfusion injury by endogenous formation of nitric oxide and of cyclo-oxygenase vasodilator metabolites. Br J Pharmacol 109:188-94, 1993.
113. Jaeschke H: Vascular oxidant stress and hepatic ischemia/reperfusion injury. Free Radic Res Commun 12:737-43, 1991.
114. Thomas GR, Thibodaux H: Transforming growth factor-beta 1 inhibits postischemic increases in splanchnic vascular resistance. Biotechnol Ther 3:91-100, 1992.
115. Woditsch I, Schrör K: Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia. Am J Physiol 263(Heart Circ Physiol 32):H1390-6, 1992.
116. Arnould T, Michiels C, Remade J: Increased PMN adherence on endothelial cells after hypoxia: involvement of PAF. CD18/CD11b, and ICAM-1. Am J Physiol 264:C1102-10, 1993.
117. Gatecel C, Mebazaa A, Kong R, et al: Inhaled nitric oxide improves hepatic tissue on oxygenation in right ventricular failure: value of hepatic venous oxygen saturation monitoring. Anesthesiology 82:588-90, 1995
118. Mitchell JR, follow DJ, Potter WZ, et al: Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther 187:185-94, 1973.
119. Dahlin DC, Miwa GT, Lu AYH, Nelson SD: N-Acetyl-p-ben-zoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proc Nat! Acad Sci USA 81:1327-31, 1984.
120. Mitchell JR, Jollow DJ, Potter WZ, et al: Acetaminophen-induced hepatic necrosis. IV. Protective role of ghitathione. J Pharmacol Exp Ther 187:211-17, 1973.
121. Holme JA, Dahlin DC, Nelson SD, Dybing E: Cytotoxic effects of N-Acetyl-p-benzoquinone imine, a common arylating intermediate of paracetamol and N'-hydroxy-paracetamol. Biochem Pharmacol 33:401-6, 1984.
122. Jewell SA, Bellomo G, Thor H, et al: Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis. Science 217:1257-9, 1982.
123. Prescott LF, Illingworth RN, Critchley JAJH, et al: Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. BMJ 2:1097-1100, 1979.
124. Harrison PM, Keays R, Bray GP, et al: Improved outcome in paracetamol-induced fulminant hepatic failure following late administration of acetylcysteine. Lancet 335:1572-3, 1990.
125. Trudell JR. Bösterling B, Trevor AJ: Reductive metabolism of carbon tetrachloride by humans cytochromes P-450 reconstituted in phosphohpid vesicles: Mass spectral identification of trichloromethyl radical bound to dioleoyl phosphatidylcholine. Proc Natl Acad Sci USA 79:2678-82, 1982.
126. Krams SM, Asher NL, Martinez OM: New immunologic insights into mechanisms of allograft rejection. In: Lake J (ed): Advances in liver transplantation. Gastroenterology Clinics of North America. Philadelphia, WB Saunders, 1993, pp 381-400.
127. Busuttil RW, Colonna II O, Hiatt JR, et al: The first 100 liver transplants at UCLA. Ann Surg 206:387-402, 1987.
128. Payen DM. Fratacci MD, Dupuy P, et al: Portal and hepatic arterial blood flow measurements of human transplanted liver by implanted Doppler probes: interest for early complications and nutrition. Surgery 107:417-27, 1990.
129. Matuschak GM (ed): Multiple systems organ failure: hepatic regulation of systemic host defense. New York, Marcel Dekker, 1993, p. 411.
130. Katz S, Jimenez MA, Lehmkuhler WE, Grosfeld JL: Liver bacterial clearance following hepatic artery ligation and portacaval shunt J Surg Res 51:267-70, 1991.
131. Mathison JC, Ulevitch RJ: The clearance, tissue distribution, and cellular localization of intravenously injected lipopohsaccharide in rabbits. J Immunol 123:2133-43, 1979.
132. Mimura Y, Sakisaka S, Harada M, et al: Role of hepatocytes in direct clearance of lipopolysaccharide in rat. Gastroenterology 109:1969-76, 1995.
133. Hewett JA, Roth RA: Hepatic and extrahepatic pathobiology of bacterial lipopolysaccharides. Pharmacol Rev 45:381-411,1993.
134. Pastor CM. Bilhar TR. Losser M-R, Payen DM: Liver injury during sepsis. J Crit Care 10:1-17, 1995.
135. Halvorsen L, Roth R, Gunther RA. et al: Liver bemodynamics during portal venous endotoxemia in swine. Circ Shock 41:166-175, 1993.
136. Pastor C, Payen D: Effect of modifying nitric oxide pathway on liver circulation in a rabbit endotoxin shock model. Shock 2:1-7. 1994.
137. Pastor CM, Losser M-R, Payen D: Nitric oxide donors prevents hepatic and systemic perfusion decrease induced by endotoxin in anesthetized rabbits. Hepatology 22:1547-53, 1995.
138. Nishida J, McCuskey RS. McDonnell D, Fox ES: Protective role of NO in hepatic microcirculatory dysfunction during endotoxemia. Am J Physiol 30 (Gastroiritest Liver Physiol 30): G1135-41, 1994.
139. Harbrecht EG, Billiar TR, Stadler J, et al: Inhibition of nitric oxide synthesis during endotoxemia promotes inrrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J Leukoc Biol 52:390-4, 1992.
140. Machtedo GW, Hurd T, Rush BF, et al: Temporal relationship of hepatocellular dysfunction and ischemia in sepsis. Arch Surg 123:424-7, 1988.
141. Wang P, Avala A. Ba ZF, et al: Tumor necrosis factor-a produces hepatocellular dysfunction despite normal cardiac output and hepatic microcirculation. Am J Physiol 265:G126-32,1993.
142. Ghosh S, Liu M-W: Decrease in adenylate cyclase activity in dog livers during endotoxic shock. 245:R737-12, 1983.
143. I-adrenergic receptors after chronic endotoxin injection. Am J Physiol 252:E699-E702, 1987.
144. 1-adrenergic receptors in rat liver during sepsis. Am J Physiol 265:R383-91, 1993.
145. Horton RA, Ceppi D, Knowles RG, Titheradge MA: Inhibition of hepatic gluconeogenesis by nitric oxide: a comparison with endotoxic shock. Biochem J 299:735-9, 1994.
146. Feingold KR, Grunfeld C: Tumor necrosis factor stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest 80:184-190, 1986.
147. Abdel-Razzak Z, Loyer P, Fautrel A, et al: Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol 44:707-15, 1993.
148. Roelofsen H, vander Veere C, Ottenhof R, et al: Decreased bilirubin transport in the perfused liver of endotoxemic rats. Gastroenterology 107.1075-84, 1994.
149. Roelofsen H. Schoemaker B, Bakker C, et al: Impaired hepatocanalicular organic anion transport in endotoxemic rats. Am J Physiol 269(Gastrointest Liver Physiol):G427-34, 1995
150. Robinson WS: Hepatitis B virus and hepatitis D virus. In: Mandell GL, Bennett JE, Dolin R (eds): Mandell. Douglas and Bennett's principles and practice of infectious disease. 4th ed. New York, Churchill Livingstone. 1995, pp 1406-34.
151. Antonucci TK, Rutter WJ: Hepatitis B virus promoters are regulated by the HBV enhancer in a tissue-specific manner. J Virol 63:579-83, 1989.
152. Houghton M. Weiner A, Han J, et al: Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology 14:381-8, 1991.
153. Hsu HH, Feinstone SM, Hoofnagle JH: Acute viral hepatitis. In: Mandell GL. Bennett JE, Dolin R (eds): Mandell Douglas and Bennett's principles and practice of infectious diseases. 4th ed. New York, Churchill Livingstone. 1995. pp 1136-53.
154. Enomoto N, Sakuma I, Asahma Y, et al. Mutations m the non-structural protein 5A gene and response to Interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 334:77-81, 1996