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International Journal of Hepatology
Volume 2011 (2011), Article ID 841407, 10 pages
http://dx.doi.org/10.4061/2011/841407
Review Article

Management of Hepatic Encephalopathy

1University College London Institute of Hepatology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK
2Department of Gastroenterology, King Georges Hospital, Barley Lane, Goodmayes, Ilford, Essex IG3 8YB, UK

Received 28 April 2011; Accepted 8 June 2011

Academic Editor: Deepak Amarapurkar

Copyright © 2011 G. Wright et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Cordoba, J. Lopez-Hellin, M. Planas et al., “Normal protein diet for episodic hepatic encephalopathy: results of a randomized study,” Journal of Hepatology, vol. 41, pp. 38–43, 2004. View at Google Scholar
  2. M. Plauth, M. Merli, J. Kondrup, A. Weimann, P. Ferenci, and M. J. Muller, “ESPEN guidelines for nutrition in liver disease and transplantation,” Clinical Nutrition, vol. 16, no. 2, pp. 43–55, 1997. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Lochs and M. Plauth, “Liver cirrhosis: rationale and modalities for nutritional support—the European Society of Parenteral and Enteral Nutrition consensus and beyond,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 2, no. 4, pp. 345–349, 1999. View at Publisher · View at Google Scholar · View at Scopus
  4. G. Marchesini, R. Marzocchi, M. Noia, and G. Bianchi, “Branched-chain amino acid supplementation in patients with liver diseases,” Journal of Nutrition, vol. 135, no. 6, pp. 1596S–1601S, 2005. View at Google Scholar · View at Scopus
  5. B. Als-Nielsen, R. L. Koretz, L. L. Kjaergard, and C. Gluud, Branched-Chain Amino Acids for Hepatic Encephalopathy (Cochrane Review), Cochrane Library, John Wiley & Sons, Chichester, UK, 2004.
  6. G. Marchesini, G. Bianchi, B. Rossi, M. Brizi, and N. Melchionda, “Nutritional treatment with branched-chain amino acids in advanced liver cirrhosis,” Journal of Gastroenterology, vol. 35, 12, pp. 7–12, 2000. View at Google Scholar · View at Scopus
  7. L. Langouche, I. Vanhorebeek, D. Vlasselaers et al., “Intensive insulin therapy protects the endothelium of critically ill patients,” Journal of Clinical Investigation, vol. 115, no. 8, pp. 2277–2286, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. N. Houstis, E. D. Rosen, and E. S. Lander, “Reactive oxygen species have a causal role in multiple forms of insulin resistance,” Nature, vol. 440, no. 7086, pp. 944–948, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. G. Marchesini, A. Fabbri, G. Bianchi, M. Brizi, and M. Zoli, “Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis,” Hepatology, vol. 23, no. 5, pp. 1084–1092, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. Z. S. Agus, I. D. Dukes, and M. Morad, “Divalent cations modulate the transient outward current in rat ventricular myocytes,” American Journal of Physiology, vol. 261, no. 2, pp. C310–C318, 1991. View at Google Scholar · View at Scopus
  11. P. Reding, J. Duchateau, and C. Bataille, “Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial,” The Lancet, vol. 2, no. 8401, pp. 493–495, 1984. View at Google Scholar · View at Scopus
  12. C. Rose, R. F. Butterworth, J. Zayed et al., “Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction,” Gastroenterology, vol. 117, no. 3, pp. 640–644, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. G. P. Layrargues, C. Rose, L. Spahr, J. Zayed, L. Normandin, and R. F. Butterworth, “Role of manganese in the pathogenesis of portal-systemic encephalopathy,” Metabolic Brain Disease, vol. 13, no. 4, pp. 311–317, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Zieve, W. M. Doizaki, and F. J. Zieve, “Synergism between mercaptans and ammonia or fatty acids in the production of coma: a possible role for mercaptans in the pathogenesis of hepatic coma,” Journal of Laboratory and Clinical Medicine, vol. 83, no. 1, pp. 16–28, 1974. View at Google Scholar · View at Scopus
  15. G. W. Elmer and L. V. McFarland, “Biotherapeutic agents in the treatment of infectious diarrhea,” Gastroenterology Clinics of North America, vol. 30, no. 3, pp. 837–854, 2001. View at Google Scholar · View at Scopus
  16. Q. Liu, Z. P. Duan, D. K. Ha, S. Bengmark, J. Kurtovic, and S. M. Riordan, “Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis,” Hepatology, vol. 39, no. 5, pp. 1441–1449, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. S. F. Solga, “Probiotics can treat hepatic encephalopathy,” Medical Hypotheses, vol. 61, no. 2, pp. 307–313, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. G. Bongaerts, R. Severijnen, and H. Timmerman, “Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy,” Medical Hypotheses, vol. 64, no. 1, pp. 64–68, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. J. Bircher, J. Muller, P. Guggenheim, and U. P. Haemmerli, “Treatment of chronic portal-systemic encephalopathy with lactulose,” The Lancet, vol. 1, no. 7443, pp. 890–892, 1966. View at Google Scholar · View at Scopus
  20. A. Bennett and K. G. Eley, “Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose,” Journal of Pharmacy and Pharmacology, vol. 28, no. 3, pp. 192–195, 1976. View at Google Scholar · View at Scopus
  21. A. Bennett and K. G. Eley, “Proceedings: stimulation of intestinal propulsion by lowered intraluminal pH,” British Journal of Surgery, vol. 63, no. 2, pp. 160–161, 1976. View at Google Scholar · View at Scopus
  22. A. Vince, M. Killingley, and O. M. Wrong, “Effect of lactulose on ammonia production in a fecal incubation system,” Gastroenterology, vol. 74, no. 3, pp. 544–549, 1978. View at Google Scholar · View at Scopus
  23. L. Agostini, P. F. Down, J. Murison, and O. M. Wrong, “Faecal ammonia and pH during lactulose administration in man: comparison with other cathartics,” Gut, vol. 13, no. 11, pp. 859–866, 1972. View at Google Scholar · View at Scopus
  24. C. Cherbut, “Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract,” Proceedings of the Nutrition Society, vol. 62, no. 1, pp. 95–99, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. B. Als-Nielsen, L. L. Gluud, and C. Gluud, “Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials.,” British Medical Journal, vol. 328, no. 7447, pp. 1046–1050, 2004. View at Google Scholar · View at Scopus
  26. S. Prasad, R. K. Dhiman, A. Duseja, Y. K. Chawla, A. Sharma, and R. Agarwal, “Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy,” Hepatology, vol. 45, no. 3, pp. 549–559, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. M. Uribe, O. Campollo, F. Vargas et al., “Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial,” Hepatology, vol. 7, pp. 639–643, 1987. View at Google Scholar
  28. J. Miquel, R. Barcena, D. Boixeda et al., “Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy,” European Journal of Gastroenterology & Hepatology, vol. 13, pp. 1067–1072, 2001. View at Google Scholar
  29. H. O. Conn, C. M. Leevy, Z. R. Vlahcevic et al., “Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial,” Gastroenterology, vol. 72, pp. 573–583, 1977. View at Google Scholar
  30. F. Miglio, D. Valpiani, S. R. Rossellini, A. Ferrieri, and N. Canova, “Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial,” Current Medical Research and Opinion, vol. 13, no. 10, pp. 593–601, 1997. View at Google Scholar · View at Scopus
  31. S. Di Piazza, M. G. Filippazzo, L. M. Valenza et al., “Rifaximine versus neomycin in the treatment of portosystemic encephalopathy,” Italian Journal of Gastroenterology, vol. 23, no. 7, pp. 403–407, 1991. View at Google Scholar · View at Scopus
  32. S. W. Brusilow, D. L. Valle, and M. L. Batshaw, “New pathways of nitrogen excretion in inborn errors of urea synthesis,” The Lancet, vol. 2, no. 8140, pp. 452–454, 1979. View at Google Scholar · View at Scopus
  33. S. W. Brusilow, “Arginine, an indispensable amino acid for patients with inborn errors of urea synthesis,” Journal of Clinical Investigation, vol. 74, no. 6, pp. 2144–2148, 1984. View at Google Scholar · View at Scopus
  34. I. Smith, “The treatment of inborn errors of the urea cycle,” Nature, vol. 291, no. 5814, pp. 378–380, 1981. View at Publisher · View at Google Scholar · View at Scopus
  35. M. L. Batshaw, S. Brusilow, and L. Waber, “Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion,” New England Journal of Medicine, vol. 306, no. 23, pp. 1387–1392, 1982. View at Google Scholar · View at Scopus
  36. S. Sushma, S. Dasarathy, R. K. Tandon, S. Jain, S. Gupta, and M. S. Bhist, “Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial,” Hepatology, vol. 16, no. 1, pp. 138–144, 1992. View at Publisher · View at Google Scholar · View at Scopus
  37. G. M. Enns, S. A. Berry, G. T. Berry, W. J. Rhead, S. W. Brusilow, and A. Hamosh, “Survival after treatment with phenylacetate and benzoate for urea-cycle disorders,” The New England Journal of Medicine, vol. 356, no. 22, pp. 2282–2292, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. M. C. Nassogne, B. Heron, G. Touati, D. Rabier, and J. M. Saudubray, “Urea cycle defects: management and outcome,” Journal of Inherited Metabolic Disease, vol. 28, no. 3, pp. 407–414, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. A. Thibault, M. R. Cooper, W. D. Figg et al., “A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer,” Cancer Research, vol. 54, no. 7, pp. 1690–1694, 1994. View at Google Scholar · View at Scopus
  40. V. Praphanphoj, S. A. Boyadjiev, L. J. Waber, S. W. Brusilow, and M. T. Geraghty, “Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia,” Journal of Inherited Metabolic Disease, vol. 23, no. 2, pp. 129–136, 2000. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Rose, A. Michalak, K. V. R. Rao, G. Quack, G. Kircheis, and R. F. Butterworth, “L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure,” Hepatology, vol. 30, no. 3, pp. 636–640, 1999. View at Publisher · View at Google Scholar · View at PubMed
  42. G. Kircheis, R. Nilius, C. Held et al., “Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study,” Hepatology, vol. 25, no. 6, pp. 1351–1360, 1997. View at Publisher · View at Google Scholar · View at PubMed
  43. U. Staedt, H. Leweling, R. Gladisch, C. Kortsik, E. Hagmuller, and E. Holm, “Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design,” Journal of Hepatology, vol. 19, no. 3, pp. 424–430, 1993. View at Google Scholar
  44. R. Jalan, G. Wright, N. A. Davies, and S. J. Hodges, “L-ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy,” Medical Hypotheses, vol. 69, no. 5, pp. 1064–1069, 2007. View at Publisher · View at Google Scholar · View at PubMed
  45. S. W. Olde Damink, N. E. P. Deutz, C. H. C. Dejong, P. B. Soeters, and R. Jalan, “Interorgan ammonia metabolism in liver failure,” Neurochemistry International, vol. 41, no. 2-3, pp. 177–188, 2002. View at Publisher · View at Google Scholar
  46. L. Zieve, C. Lyftogt, and D. Raphael, “Ammonia toxicity: comparative protective effect of various arginine and ornithine derivatives, aspartate, benzoate, and carbamyl glutamate,” Metabolic Brain Disease, vol. 1, no. 1, pp. 25–35, 1986. View at Google Scholar
  47. N. A. Davies, G. Wright, L. M. Ytrebo et al., “L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats,” Hepatology, vol. 50, no. 1, pp. 155–164, 2009. View at Publisher · View at Google Scholar · View at PubMed
  48. L. M. Ytrebø, R. G. Kristiansen, H. Maehre et al., “L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure,” Hepatology, vol. 50, pp. 165–174, 2009. View at Google Scholar
  49. S. Gentile, G. Guarino, M. Romano et al., “A randomized controlled trial of acarbose in hepatic encephalopathy,” Clinical Gastroenterology and Hepatology, vol. 3, no. 2, pp. 184–191, 2005. View at Publisher · View at Google Scholar
  50. M. Y. Morgan, A. Jakobovits, and A. Elithorn, “Successful use of bromocriptine in the treatment of a patient with chronic portasystemic encephalopathy,” The New England Journal of Medicine, vol. 296, no. 14, pp. 793–794, 1977. View at Google Scholar
  51. M. Y. Morgan, A. W. Jakobovits, I. M. James, and S. Sherlock, “Successful use of bromocriptine in the treatment of chronic hepatic encephalopathy,” Gastroenterology, vol. 78, no. 4, pp. 663–670, 1980. View at Google Scholar
  52. M. Uribe, A. Farca, and M. A. Marquez, “Treatment of chronic portal systemic encephalopathy with bromocriptine: a double-blind controlled trial,” Gastroenterology, vol. 76, no. 6, pp. 1347–1351, 1979. View at Google Scholar
  53. B. Bernard, J. D. Grange, E. N. Khac, X. Amiot, P. Opolon, and T. Poynard, “Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis,” Hepatology, vol. 29, no. 6, pp. 1655–1661, 1999. View at Publisher · View at Google Scholar · View at PubMed
  54. M. C. Hou, H. C. Lin, T. T. Liu et al., “Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial,” Hepatology, vol. 39, no. 3, pp. 746–753, 2004. View at Publisher · View at Google Scholar · View at PubMed
  55. O. Riggio, A. Masini, C. Efrati et al., “Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study,” Journal of Hepatology, vol. 42, no. 5, pp. 674–679, 2005. View at Publisher · View at Google Scholar · View at PubMed
  56. A. J. Makin, J. Wendon, and R. Williams, “A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993),” Gastroenterology, vol. 109, no. 6, pp. 1907–1916, 1995. View at Publisher · View at Google Scholar
  57. R. Jalan and D. Kapoor, “Reversal of diuretic-induced hepatic encephalopathy with infusion of albumin but not colloid,” Clinical Science, vol. 106, no. 5, pp. 467–474, 2004. View at Publisher · View at Google Scholar · View at PubMed
  58. D. L. Shawcross, N. A. Davies, R. Williams, and R. Jalan, “Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis,” Journal of Hepatology, vol. 40, no. 2, pp. 247–254, 2004. View at Publisher · View at Google Scholar
  59. R. J. Ede, A. E. S. Gimson, D. Bihari, and R. Williams, “Controlled hyperventilation in the prevention of cerebral oedema in fulminant hepatic failure,” Journal of Hepatology, vol. 2, no. 1, pp. 43–51, 1986. View at Google Scholar
  60. A. Davenport, E. J. Will, and A. M. Davison, “Effect of posture on intracranial pressure and cerebral perfusion pressure in patients with fulminant hepatic and renal failure after acetaminophen self-poisoning,” Critical Care Medicine, vol. 18, no. 3, pp. 286–289, 1990. View at Google Scholar
  61. G. Strauss, B. A. Hansen, G. M. Knudsen, and F. S. Larsen, “Hyperventilation restores cerebral blood flow autoregulation in patients with acute liver failure,” Journal of Hepatology, vol. 28, no. 2, pp. 199–203, 1998. View at Publisher · View at Google Scholar
  62. E. F. M. Wijdicks and S. L. Nyberg, “Propofol to control intracranial pressure in fulminant hepatic failure,” Transplantation Proceedings, vol. 34, no. 4, pp. 1220–1222, 2002. View at Publisher · View at Google Scholar
  63. A. Ellis and J. Wendon, “Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management,” Seminars in Liver Disease, vol. 16, no. 4, pp. 379–387, 1996. View at Google Scholar
  64. R. Jalan, “Acute liver failure: current management and future prospects,” Journal of Hepatology, vol. 42, no. 1, pp. S115–S123, 2005. View at Publisher · View at Google Scholar · View at PubMed
  65. M. H. Davies, D. Mutimer, J. Lowes, E. Elias, and J. Neuberger, “Recovery despite impaired cerebral perfusion in fulminant hepatic failure,” The Lancet, vol. 343, no. 8909, pp. 1329–1330, 1994. View at Publisher · View at Google Scholar
  66. R. Jalan, “Intracranial hypertension in acute liver failure: pathophysiological basis of rational management,” Seminars in Liver Disease, vol. 23, no. 3, pp. 271–282, 2003. View at Publisher · View at Google Scholar · View at PubMed
  67. R. Harry, G. Auzinger, and J. Wendon, “The clinical importance of adrenal insufficiency in acute hepatic dysfunction,” Hepatology, vol. 36, no. 2, pp. 395–402, 2002. View at Publisher · View at Google Scholar · View at PubMed
  68. K. Moore, “Renal failure in acute liver failure,” European Journal of Gastroenterology & Hepatology, vol. 11, no. 9, pp. 967–975, 1999. View at Google Scholar
  69. A. Davenport, E. J. Will, A. M. Davison et al., “Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy,” Nephron, vol. 53, no. 2, pp. 142–146, 1989. View at Google Scholar
  70. R. J. Winney, D. M. Kean, J. J. K. Best, and M. A. Smith, “Changes in brain water with haemodialysis,” The Lancet, vol. 2, no. 8515, pp. 1107–1108, 1986. View at Google Scholar
  71. A. Davenport, E. J. Will, and A. M. Davidson, “Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure,” Critical Care Medicine, vol. 21, no. 3, pp. 328–338, 1993. View at Google Scholar
  72. N. D. Murphy, S. K. Kodakat, J. A. Wendon et al., “Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation,” Critical Care Medicine, vol. 29, no. 11, pp. 2111–2118, 2001. View at Google Scholar
  73. R. Jalan, K. Dabos, D. N. Redhead, A. Lee, and P. C. Hayes, “Elevation of intracranial pressure following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage,” Journal of Hepatology, vol. 27, no. 5, pp. 928–933, 1997. View at Publisher · View at Google Scholar
  74. J. Cordoba, J. Gottstein, and A. T. Blei, “Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis,” Journal of Hepatology, vol. 29, no. 4, pp. 589–594, 1998. View at Publisher · View at Google Scholar
  75. N. Murphy, G. Auzinger, W. Bernel, and J. Wendon, “The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure,” Hepatology, vol. 39, no. 2, pp. 464–470, 2004. View at Publisher · View at Google Scholar · View at PubMed
  76. N. Rolando, J. Philpott-Howard, and R. Williams, “Bacterial and fungal infection in acute liver failure,” Seminars in Liver Disease, vol. 16, no. 4, pp. 389–402, 1996. View at Google Scholar
  77. N. Rolando, J. J. Wade, A. Stangou et al., “Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure,” Liver Transplantation and Surgery, vol. 2, no. 1, pp. 8–13, 1996. View at Google Scholar
  78. N. Rolando, F. Harvey, J. Brahm et al., “Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients,” Hepatology, vol. 11, no. 1, pp. 49–53, 1990. View at Google Scholar
  79. N. Rolando, J. Wade, M. Davalos, J. Wendon, J. Philpott-Howard, and R. Williams, “The systemic inflammatory response syndrome in acute liver failure,” Hepatology, vol. 32, no. 4 I, pp. 734–739, 2000. View at Google Scholar
  80. J. Canalese, A. E. S. Gimson, and C. Davis, “Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure,” Gut, vol. 23, no. 7, pp. 625–629, 1982. View at Google Scholar
  81. M. A. Hanid, M. Davies, P. J. Mellon et al., “Clinical monitoring of intracranial pressure in fulminant hepatic failure,” Gut, vol. 21, pp. 866–869, 1980. View at Google Scholar
  82. R. Jalan and R. Williams, “The inflammatory basis of intracranial hypertension in acute liver failure,” Journal of Hepatology, vol. 34, no. 6, pp. 940–942, 2001. View at Publisher · View at Google Scholar
  83. R. Jalan, A. Pollok, S. H. A. Shah, K. K. Madhavan, and K. J. Simpson, “Liver derived pro-inflammatory cytokines may be important in producing intracranial hypertension in acute liver failure,” Journal of Hepatology, vol. 37, no. 4, pp. 536–538, 2002. View at Publisher · View at Google Scholar
  84. M. Peignoux, J. Bernuau, and J. P. Benhamou, “Total hepatectomy and hepatic vascular exclusion in the rat: a comparison, with special reference to the influence of body temperature,” Clinical Science, vol. 62, no. 3, pp. 273–277, 1982. View at Google Scholar
  85. P. Traber, M. DalCanto, D. Ganger, and A. T. Blei, “Effect of body temperature on brain edema and encephalopathy in the rat after hepatic devascularization,” Gastroenterology, vol. 96, no. 3, pp. 885–891, 1989. View at Google Scholar
  86. S. Eguchi, A. Kamlot, J. Ljubimova et al., “Fulminant hepatic failure in rats: Survival and effect on blood chemistry and liver regeneration,” Hepatology, vol. 24, no. 6, pp. 1452–1459, 1996. View at Publisher · View at Google Scholar
  87. R. Jalan, S. W. M. O. Damink, N. E. P. Deutz, A. Lee, and P. C. Hayes, “Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure,” The Lancet, vol. 354, no. 9185, pp. 1164–1168, 1999. View at Publisher · View at Google Scholar
  88. R. Jalan, S. W. M. Olde Damink, N. E. P. Deutz, P. C. Hayes, and A. Lee, “Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension,” Gastroenterology, vol. 127, no. 5, pp. 1338–1346, 2004. View at Publisher · View at Google Scholar
  89. G. I. Strauss, G. M. Knudsen, J. Kondrup, K. Moller, and F. S. Larsen, “Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure,” Gastroenterology, vol. 121, no. 5, pp. 1109–1119, 2001. View at Google Scholar
  90. A. Forbes, G. J. M. Alexander, J. G. O'Grady et al., “Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure,” Hepatology, vol. 10, no. 3, pp. 306–310, 1989. View at Google Scholar
  91. G. R. Bernard, A. P. Wheeler, J. A. Russell et al., “The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in sepsis study group,” The New England Journal of Medicine, vol. 336, no. 13, pp. 912–918, 1997. View at Publisher · View at Google Scholar · View at PubMed
  92. O. R. Cauli, R. Piedrafita, B. Boix, and J. B. Felipo, “Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with chronic liver failure,” Hepatology, vol. 46, no. 2, pp. 514–519, 2007. View at Google Scholar
  93. K. Jensen, J. Ohrstrom, G. E. Cold, and J. Astrup, “Indomethacin (Confortid) in severe head injury and elevated intracranial pressure (ICP),” Acta Neurochirurgica Supplementum, vol. 55, pp. 47–48, 1992. View at Google Scholar
  94. F. Tofteng and F. S. Larsen, “The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure,” Journal of Cerebral Blood Flow and Metabolism, vol. 24, no. 7, pp. 798–804, 2004. View at Google Scholar
  95. M. S. Abdel-Halim, B. Sjoquist, and E. Anggard, “Inhibition of prostaglandin synthesis in rat brain,” Acta Pharmacol Toxicol, vol. 43, pp. 266–272, 1978. View at Google Scholar
  96. A. J. Ellis, J. A. Wendon, and R. Williams, “Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial,” Hepatology, vol. 32, no. 3, pp. 536–541, 2000. View at Google Scholar
  97. P. M. Harrison, R. Keays, G. P. Bray, G. J. M. Alexander, and R. Williams, “Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine,” The Lancet, vol. 335, no. 8705, pp. 1572–1573, 1990. View at Publisher · View at Google Scholar
  98. R. Keays, P. M. Harrison, J. A. Wendon et al., “Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial,” British Medical Journal, vol. 303, no. 6809, pp. 1026–1029, 1991. View at Google Scholar
  99. Z. Ben-Ari, H. Vaknin, and R. Tur-Kaspa, “N-acetylcysteine in acute hepatic failure (non-paracetamol-induced),” Hepato-Gastroenterology, vol. 47, no. 33, pp. 786–789, 2000. View at Google Scholar
  100. G. Barbaro, G. Di Lorenzo, M. Soldini et al., “Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo-controlled, cross-over study,” Hepatology, vol. 28, no. 2, pp. 374–378, 1998. View at Publisher · View at Google Scholar · View at PubMed
  101. K. D. Mullen, P. Amodio, and M. Y. Morgan, “Therapeutic studies in hepatic encephalopathy,” Metabolic Brain Disease, vol. 22, no. 3-4, pp. 407–423, 2007. View at Publisher · View at Google Scholar · View at PubMed
  102. S. Mechtcheriakov, I. W. Graziadei, M. Mattedi et al., “Incomplete improvement of visuo-motor deficits in patients with minimal hepatic encephalopathy after liver transplantation,” Liver Transplantation, vol. 10, no. 1, pp. 77–83, 2004. View at Publisher · View at Google Scholar · View at PubMed
  103. S. Sen, R. Jalan, and R. Williams, “Liver failure: basis of benefit of therapy with the molecular adsorbents recirculating system,” International Journal of Biochemistry and Cell Biology, vol. 35, no. 9, pp. 1306–1311, 2003. View at Publisher · View at Google Scholar
  104. V. Stadlbauer, N. A. Davies, S. Sen, and R. Jalan, “Artificial liver support systems in the management of complications of cirrhosis,” Seminars in Liver Disease, vol. 28, no. 1, pp. 96–109, 2008. View at Publisher · View at Google Scholar · View at PubMed
  105. B. Ringe, N. Lubbe, E. Kuse, U. Frei, and R. Pichlmayr, “Total hepatectomy and liver transplantation as two-stage procedure,” Annals of Surgery, vol. 218, no. 1, pp. 3–9, 1993. View at Google Scholar
  106. D. Shawcross and R. Jalan, “Dispelling myths in the treatment of hepatic encephalopathy,” The Lancet, vol. 365, no. 9457, pp. 431–433, 2005. View at Publisher · View at Google Scholar · View at PubMed