Advertisement

Hepatic Encephalopathy

  • Gerald Y. Minuk
Part of the Topics in Gastroenterology book series (TGEN)

Abstract

Hepatic encephalopathy is a complex neurological disorder associated with advanced liver disease of either acute or chronic nature. The etiology of this disorder has confounded investigators since it was first described by Hippocrates in 460–370 B.C. One reason why the pathogenesis has remained so elusive for so long is that our understanding of normal consciousness remains relatively incomplete. Another is that much of the research past and present has been carried out in animal models of acute or, less commonly, chronic liver disease and whether the results of these studies can be extrapolated to humans remains to be determined. Finally, there is tremendous compartmentation and functional heterogeneity throughout the brain and the sophisticated techniques required to study specific regions or, more precisely, the specific synapses responsible for disturbed levels of consciousness have yet to be developed. Despite these limitations, sufficient experimental data are available to state that normal brain function in humans is dependent on at least three important factors: (1) adequate oxygenation, (2) adequate glucose or nutritional support, and (3) intact neurotransmitter systems. Thus, disturbances in any one of these three areas could conceivably result in an alteration in normal consciousness.

Keywords

Hepatic Encephalopathy Aromatic Amino Acid Advanced Liver Disease Hepatic Coma Portal Systemic Encephalopathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Maiolo AT, Bianchi Porro G, Galli C et al. Brain energy metabolism in hepatic coma. Adv Exp Biol Med 1971;4:52–70.Google Scholar
  2. 2.
    Geiger A, Yamasaki S. Cytidine and uridine requirement of the brain. J Neurochem 1956;1:93–100.PubMedCrossRefGoogle Scholar
  3. 3.
    Shafer WH, Isselbacher KJ. Uridine metabolism in chronic liver disease. Gastroenterology 1961;40:782–784.PubMedGoogle Scholar
  4. 4.
    Nance FV, Batson RC, Kline DG. Ammonia production in germ-free ECK fistula dog. Surgery 1971;70:169–174.PubMedGoogle Scholar
  5. 5.
    Summerskill WHJ, Wolfe SJ. The metabolism of ammonia and aketo acids in liver disease and hepatic coma. J Clin Invest 1957;36:361–372.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Lockwood AH, McDonald JM, Reiman RE, Gelbard AS, Laughlin JS, Duffy TE, Plum F. The dynamics of ammonia metabolism in man. Effect of liver disease and hyperammonemia. J Clin Invest 1979;63:449–460.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Hindfelt B, Plum F, Duffy TE. Effect of acute ammonia intoxication or cerebral metabolism in rat with portacaval shunts. J Clin Invest 1977;59:386–396.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Conn HO, Lieberthal MM. The Hepatic Coma Syndromes and Lactulose. Baltimore: Williams and Wilkins, 1979.Google Scholar
  9. 9.
    Flannery DB, Hsia YE, Wolf B. Current status of hyperammonemic syndromes. Hepatology 1982;2:495–506.PubMedCrossRefGoogle Scholar
  10. 10.
    Ficher CJ, Faloon WW. Blood ammonia levels in hepatic cirrhosis: Their control by oral administration of neomycin. N Engl J Med 1957;256:1030–1035.CrossRefGoogle Scholar
  11. 11.
    Crossley IR, Williams R. Progress in the treatment of chronic portosystemic encephalopathy. Gut 1984;25:85–98.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Pappas SC, Ferenci P, Schafer DF, Jones EA. Visual evoked potentials: hepatic encephalopathy resembles the post-ictal state but differs from hyperammonemia. Hepatology 1982 (abstract) 2:708.Google Scholar
  13. 13.
    Plum F, Hindfelt B. The neurological complication of liver disease. In: Metabolic and Deficiency Diseases of the Nervous System, Part I (Vinken PJ, Bruyn GW, eds). New York: Elsevier, 1976, pp. 346–377.Google Scholar
  14. 14.
    Zieve L. The mechanism of hepatic coma. Hepatology 1981;1:360–365.PubMedCrossRefGoogle Scholar
  15. 15.
    Zieve L, Nicoloff DM. Pathogenesis of hepatic coma. Ann Rev Med 1975;26:143–157.PubMedCrossRefGoogle Scholar
  16. 16.
    Fischer JE, Baldessarini RJ. False neurotransmitters and hepatic failure. Lancet 1971;2:75–79.PubMedCrossRefGoogle Scholar
  17. 17.
    Soeters P, Fischer JE. Lancet 1976;2:880–882.PubMedCrossRefGoogle Scholar
  18. 18.
    Vilstrup H, Bucher D, Krog B, Damgard SE. Amino acid clearance in cirrhosis. Eur J Clin Invest 1979;12:197.CrossRefGoogle Scholar
  19. 19.
    Fossi-Fanelli F, Angelico M, Cangiano C, Cascino A, Capocaccia R, Deconciliis D, Riggio O, Capocaccia L. Effect of glucose and/or branched chain amino acid infusion on plasma amino acid inbalance in chronic liver failure. J Parenter Enteral Nutr 1981;5:414.CrossRefGoogle Scholar
  20. 20.
    James JH, Ziparo V, Jepson B, Fischer JE. Hyperammonaemia plasma amino acid inbalance and blood-brain aminoacid transport: A unified theory of portal-systemic encephalopathy. Lancet 1979;2:772–775.PubMedCrossRefGoogle Scholar
  21. 21.
    Zieve L, Olsen EL. Can hepatic coma be caused by a reduction of brain nonadrenaline or dopamine? Gut 1977;18:688–691.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Curzon G, Knott PJ. Environmental, toxicological and related aspects of tryptophan metabolism with particular reference to the central nervous system. CRC Crit Rev Toxicol 1977; September:145–187.Google Scholar
  23. 23.
    Fischer JE, Baldessarini RJ. Pathogenesis and therapy of hepatic coma. In: Progress in Liver Diseases, Vol 5 (Popper H, Schaffner F, eds). New York: Grune and Stratton, 1975, pp. 363–387.Google Scholar
  24. 24.
    Hoyumpa AM, Jr, Schenker S. Perspectives in hepatic encephalopathy. J Lab Clin Med 1982;100:477–487.PubMedGoogle Scholar
  25. 25.
    Michel H, Solere M, Granier P et al. Treatment of cirrhotic hepatic encephalopathy with L-dopa. A controlled trial. Gastroenterology 1980;79:207–211.PubMedGoogle Scholar
  26. 26.
    Uribe M, Farca A, Maquez MA et al. Treatment of chronic portal systemic encephalopathy with bromocriptine. A double blind controlled trial. Gastroenterology 1979;76:1347–1351.PubMedGoogle Scholar
  27. 27.
    Schafer DF, Jones EA. Hepatic encephalopathy and γ-amino-butyric acid neurotransmitter system. Lancet 1982;1:18–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Schafer DF, Jones EA. Potential neural mechanisms in the pathogenesis of hepatic encephalopathy. In: Progress in Liver Diseases, Vol 7 (Popper H, Schaffner F, eds). Orlando: Grune and Stratton, 1982, pp. 615–627.Google Scholar
  29. 29.
    Hoyumpa AM. The unfolding GABA story. Hepatology 1986;6(5): 1042–1044.PubMedCrossRefGoogle Scholar
  30. 30.
    Schafer DF, Fowler JM, Jones EA. Colonic bacteria: A source of γ-aminobutyric acid in blood. Proc Soc Exp Biol Med 1981;167:301–303.PubMedCrossRefGoogle Scholar
  31. 31.
    Minuk GY. Gamma-aminobutyric acid (GABA) production by eight common bacterial pathogens. Scand J Infect Dis 1986;18:465–467.PubMedCrossRefGoogle Scholar
  32. 32.
    van Berlo CLH, deJonge HR, van den Bogaard AEJM, van Eijk HMH, Janssen MA, Soeters PB. γ-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Gastroenterology 1987;92:472–479.Google Scholar
  33. 33.
    Ferenci P, Schafer DF, Schrager R, Jones EA. Metabolism of the inhibitory neurotransmitter γ-Aminobutyric acid in a rabbit model of acute hepatic failure. Hepatology 1981;1:509–512.Google Scholar
  34. 34.
    Minuk GY, Vergalla J, Ferenci P, Jones EA. Identification of an acceptor system of gamma-aminobutyric acid on isolated rat hepatocytes. Hepatology 1984;4:180–185.PubMedCrossRefGoogle Scholar
  35. 35.
    Minuk GY, Sarjeant EJ. The effect of (a) neomycin and lactulose treatment on systemic and portal serum GABA levels in rats and (b) pH changes on [3H]GABA binding to isolated rat hepatocytes. Proceedings of Sixth International Symposium on Ammonia, Amino Acids and Hepatic Encephalopathy, Maastricht, The Netherlands (in press).Google Scholar
  36. 36.
    Zieve L. Hepatic encephalopathy. In: Diseases of the Liver, 5th ed (Schiff L, Schiff ER, eds). Philadelphia: J.B. Lippincott, Co., 1982, p. 433.Google Scholar
  37. 37.
    Ferenci P, Schafer DF, Kleinberger G, Hoofnagle JH, Jones EA. Serum levels of gamma-aminobutyric acid-like activity in acute and chronic hepatocellular diseases. Lancet 1983;1:811–814.CrossRefGoogle Scholar
  38. 38.
    Minuk GY, Winder A, Burgess ED, Sarjeant EJ. Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy. Hepatolgastroenterology 1985;32:171–174.Google Scholar
  39. 39.
    Minuk GY, Sarjeant EJ, Buchan K. Elevated serum γ-amino-butyric acid levels in children with Reye’s syndrome. J Paed Gastroenterology Nutr 1985;4:528–531.CrossRefGoogle Scholar
  40. 40.
    Maddison JE, Dodd PR, Morrison M, Johnston GAR, Farrell GC. Plasma GABA, GABA-like activity and the brain GABA benzodiazepine receptor complex in rat with chronic hepatic encephalopathy. Hepatology 1987;7:621–628.PubMedCrossRefGoogle Scholar
  41. 41.
    Hare TA, Manyam NVB. Rapid and sensitive ion-exchange fluorometric measurement of γ-Aminobutyric acid in physiological fluids. Anal Biochem 1980;101:349–355.PubMedCrossRefGoogle Scholar
  42. 42.
    Zeneroli ML, Iuliano E, Racagni G et al. Metabolism and brain uptake of γ-minobutyric acid in galactosamine-induced hepatic encephalopathy in rats. J Neurochem 1982;38:1219–1222.PubMedCrossRefGoogle Scholar
  43. 43.
    Loscher W, Frey HH. Transport of GABA at the blood-CSF interface. J Neurochem 1982;38:1072–1079.PubMedCrossRefGoogle Scholar
  44. 44.
    Horowitz ME, Schafer DF, Molnar P et al. Increased blood brain transfer in a rabbit model of acute liver failure. Gastroenterology 1983;84:1003–1011.PubMedGoogle Scholar
  45. 45.
    Bassett ML, Mullen KD, Scholz B et al. Increased brain GABA uptake in pre-coma encephalopathy in a rabbit model of fulminant hepatic failure. Hepatology 1985 (abstract); 5:1032.Google Scholar
  46. 46.
    Tallman JF, Gallager DW. The GABAergic system: A locus of benzodiazepine action. Ann RevNeurosci 1985;8:21–44.PubMedCrossRefGoogle Scholar
  47. 47.
    Harris AR, Allan AM. Functional coupling of γ-Aminobutyric acid receptors to chloride channels in brain membranes. Sciences 1985:228:1108–1110.CrossRefGoogle Scholar
  48. 48.
    Jones EA, Schafer DF, Ferenci P et al. The neurobiology of hepatic encephalopathy. Hepatology 1984;4:1235–1242.PubMedCrossRefGoogle Scholar
  49. 49.
    Baraldi M, Zeneroli ML. Experimental hepatic encephalopathy: Changes in the binding of γ-Aminobutyric acid. Sciences 1982;216:427–428.CrossRefGoogle Scholar
  50. 50.
    Zeneroli ML, Baraldi M, Pinelli G et al. Brain receptor changes in portal-systemic encephalopathy in dogs. Hepatology 1985 (abstract);5:953.CrossRefGoogle Scholar
  51. 51.
    Jones EA. Hepatic encephalopathy update. Viewpoint Dig Dis 1986;18:1–4.Google Scholar
  52. 52.
    Maddison JE, Dodd PR, Johnston GAR, Farrell GC. Brain γ-Aminobutyric acid receptor binding is normal in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma γ-Aminobutyric acid-like activity. Gastroenterology 1987;93:1062–1068.PubMedGoogle Scholar
  53. 53.
    Zeneroli ML, Ventura E, Baraldi M et al. Visual evoked potentials in encephalopathy induced by galactosamine, ammonia, dimethyldisulfide and octanoic acid. Hepatology 1982;2:532–538.PubMedCrossRefGoogle Scholar
  54. 54.
    Pappas SC, Jones EA. Methods for asserting hepatic encephalopathy. Semin Liver Dis 1983;3:298–307.PubMedCrossRefGoogle Scholar
  55. 55.
    Bassett ML, Mullen KD, Skolnick P et al. GABA and benzodiazepine receptor antagonist ameliorate hepatic encephalopathy in a rabbit model of fulminant hepatic failure. Hepatology 1985(abstract); 5:1032.Google Scholar
  56. 56.
    Baraldi M, Zeneroli ML, Ventura E et al. Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist. Clin Sci 1984;67:167–175.PubMedGoogle Scholar
  57. 57.
    Scollo-Lavizzari G, Steinmann E. Reversal of hepatic coma by benzodiazepine antagonist (Ro 15–1788). Lancet 1985;1:1324.CrossRefGoogle Scholar
  58. 58.
    Bansky G, Meier PJ, Ziegler WH et al. Reversal of hepatic coma by benzodiazepine antagonist (Ro 15–1788). Lancet 1985;1:1324–1325.Google Scholar
  59. 59.
    Moroni F, Riggio O, Carla V, Festuccia V et al. Hepatic encephalopathy: Lack of changes of γ-Aminobutyric acid content in plasma and cerebrospinal fluid. Hepatology 1987;7:816–820.PubMedCrossRefGoogle Scholar
  60. 60.
    Pomier-Layrargues, Bories P, Mirouze D, Giordan J, Feneyrou B, Bellet-Hermann H, Marchai G, Michel H. Brain gamma amino-butyric acid in acute hepatic encephalopathy in dogs following hepatectomy with or without abdominal evisceration. In: Hepatic Encephalopathy in Chronic Liver Failure (Capocaccia L, Fischer JE, Rossi-Fanelli F, ed). New York: Plenum Press, 1984, pp. 127–134.Google Scholar
  61. 61.
    Lavoie J, Giguere JF, Layrargues GP, Butterworth RF. Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J Neurochem 1987;49:692–697.PubMedCrossRefGoogle Scholar
  62. 62.
    Butterworth RF, Giguere JF. Cerebral aminoacids in portasystemic encephalopathy: Lack of evidence for altered γ-Aminobutyric acid (GABA) function. Metabol Brain Dis 1986;1:221–228.CrossRefGoogle Scholar
  63. 63.
    Rzepczynski D, Zieve L, Lindblad S, LaFontaine D. In vivo studies of GABAergic effect in experimental hepatic encephalopathy. Hepatology 1986;6:902–905.PubMedCrossRefGoogle Scholar
  64. 64.
    Levy DE, Bates D, Caronna JJ et al. Prognosis in non-traumatic coma. Ann Intern Med 1981;94:293–301.PubMedCrossRefGoogle Scholar
  65. 65.
    Giguere JF, Butterworth RF. Amino acid changes in regions of the CNS in relation to function in experimental portal-systemic encephalopathy. Neurochem Res 1984;9:1307–1319.Google Scholar
  66. 66.
    Gilbertstadt S, Gilbertstadt H, Buegel B, Collier R, McClain CF, Zieve L. Defective intellectual function in alcoholic cirrhotics and non-cirrhotic alcoholics: Relationship to severity of liver disease. Gastroenterology 1978 (abstract); 74:1037.Google Scholar
  67. 67.
    Elsass P, Lund Y, Ranek L. Encephalopathy in patients with cirrhosis of the liver: a neuropsychological study. Scand J Gastroenterol 1978;13:241–247.PubMedCrossRefGoogle Scholar
  68. 68.
    Rikkers L, Jenko P, Rudman D, Freides D. Subclinical hepatic encephalopathy: Detection, prevalence and relationship to nitrogen metabolism. Gastroenterology 1978;75:462–469.PubMedGoogle Scholar
  69. 69.
    Conn HO. Trailmaking and number-connection test in the assessment of mental state in portal systemic encephalopathy. Dig Sci Dis 1977;22:541–550.CrossRefGoogle Scholar
  70. 70.
    Parsons-Smith BG, Summerskill WHJ, Dawson AM, Sherlock S. The electroencephalograph in liver disease. Lancet 1957;2:867–871.CrossRefGoogle Scholar
  71. 71.
    Yaar I, Shapiro MB, Pottala EW. Spectral analysis of the EEG in hepatic encephalopathy treated with levodopa. Electroencephalog Clin Neurophysiol 1981;52:617–625.CrossRefGoogle Scholar
  72. 72.
    MacGillivray BB. The EEG in liver diseases. In: Handbook of EEG and Clinical Neurophysiology, Vol 15 (MacGillivray BB, ed). Amsterdam: Elsevier, pp. 26–50.Google Scholar
  73. 73.
    Cobb WA, Dawson GD. The latency and form in many of the occipital potentials evoked by bright flashes. J Physiol 1960;152:108–121.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Schafer DF, Pappas SC, Brody LE, Jacobs R, Jones EA. Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas. Gastroenterology 1984;86:540–545.PubMedGoogle Scholar
  75. 75.
    Zeneroli ML, Ventura E, Baraldi M et al. Visual evoked potentials in encephalopathy induced by galactosamine, ammonia, dimethyldisulfide and octanoic acid. Hepatology 1982;2:532–538.PubMedCrossRefGoogle Scholar
  76. 76.
    Pappas C, Ferenci P, Schafer DF, Jones EA. Visual evoked potential in a rabbit model of hepatic encephalopathy. II. Comparisons of hyperammonemic encephalopathy, postictal coma, and coma induced by synergistic neurotoxins. Gastroenterology 1984;86:546–551.PubMedGoogle Scholar
  77. 77.
    Conn HO. The hepatic coma syndrome. Warren-Teed GI Tract 1974;4:18–23.Google Scholar
  78. 78.
    Greenberger NJ, Carley J, Schenker S, Bettinger I, Stamnes C, Beyer P. Effect of vegetable and animal protein diets in chronic hepatic encephalopathy. Am J Dig Dis 1977;22:845.PubMedCrossRefGoogle Scholar
  79. 79.
    Sherlock S, Summerskill WHJ, White LP, et al. Portal systemic encephalopathy. Neurological complications of liver disease. Lancet 1954;2:453–457.CrossRefGoogle Scholar
  80. 80.
    Swart GR, Frenkel M, van de Berg JWO. Minimum protein requirements in advanced liver disease; a metabolic study of the effect of oral branched chain amino acids. In: Metabolism and Clinical Implications of Branched Chain Amino and Keto Acids (Walser M, Williamson JR, eds). New York: Elsevier, 1981, pp. 427–432.Google Scholar
  81. 81.
    Dawson AM, McLaren J, Sherlock S. Neomycin in the treatment of hepatic coma. Lancet 1957;2:1263–1268.CrossRefGoogle Scholar
  82. 82.
    Fast BB, Wolfe SJ, Stormont J, Davidson CS. Antibiotic therapy in the management of hepatic coma. Arch Intern Med 1958;101:467–475.CrossRefGoogle Scholar
  83. 83.
    Bircher J, Muller J, Guggenheim P, Haemmerli UP. Treatment of chronic portal systemic encephalopathy with lactulose. Lancet 1966;1:890–892.PubMedGoogle Scholar
  84. 84.
    Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy: A double blind clinical trial. N Engl J Med 1969;281:408–412.PubMedCrossRefGoogle Scholar
  85. 85.
    Simmons F, Goldstein H, Boyle JD. A controlled clinical trial of lactulose in hepatic encephalopathy. Gastroenterology 1970;59:827–832.PubMedGoogle Scholar
  86. 86.
    Bircher J, Haemmerli UP, Scolio-Lavizzari G, Hoffman K. Treatment of chronic portal-systemic encephalopathy with lactulose. Report of six patients and review of the literature. Am J Med 1971;51:148–159.PubMedCrossRefGoogle Scholar
  87. 87.
    Uribe M, Campollo O, Vargas F, Ravelli GP, Mundo F, Zapata L, Gil S, Garcia-Ramos G. Acidifying enemas (lactitol and lactulose) vs nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: A double-blind randomized clinical trial. Hepatology 1987;7(4):639–643.PubMedCrossRefGoogle Scholar
  88. 88.
    Weber FL. Therapy of portal-systemic encephalopathy: The practical and the promising. Gastroenterology 1981;81:174–177.PubMedGoogle Scholar
  89. 89.
    Pirotte J, Guffens JM, Devos J. Comparative study of basal arterial ammonaemia and of orally induced hyperammonaemia in chronic portal systemic encephalopathy treated with neomycin, lactulose and association of neomycin and lactulose. Digestion 1974;10:435–444.PubMedCrossRefGoogle Scholar
  90. 90.
    Conn HO, Lieberthal MM. Lactulose and neomycin: Combined therapy. In: The Hepatic Coma Syndromes and Lactulose. Baltimore: Williams and Wilkins, 1978, pp. 340–345.Google Scholar
  91. 91.
    Weber FL, Fresard KM, Lally BR. Effect of lactulose and neomycin on urea metabolism in cirrhotic subjects. Gastroenterology 1982;82:213–217.PubMedGoogle Scholar
  92. 92.
    Castell DO, Moore EW. Ammonia absorption from the human colon. The role of non-ionic diffusion. Gastroenterology 1971;60:33–42.PubMedGoogle Scholar
  93. 93.
    Herlong HF, Maddrey WC, Walser M. The use of orthinine salt of branched-chain keto acids in portal-systemic encephalopathy. Ann Intern Med 1980;93:545–550.PubMedCrossRefGoogle Scholar
  94. 94.
    Eriksson LS, Persson A, Wahren J. Branched-chain amino acids in the treatment of chronic hepatic encephalopathy. Gut 1982;23:801–806.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    McGhee A, Henderson JM, Milliken WJ, Bleir J. Comparison of the effect of hepaticaid and casein modular diets on encephalopathy, plasma amino acids and nitrogen balance in cirrhotic patients. Ann Surg 1983;197:288–293.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Michel H, Solere M, Granier P, Cavvet G, Bali JP, Pons F, Bellet-Hermann H. Treatment of cirrhotic hepatic encephalopathy with L-dopa. A controlled trial. Gastroenterology 1980;79:207–211.PubMedGoogle Scholar
  97. 97.
    Morgan MH, Read AE, Speller DCE. Treatment of hepatic encephalopathy with metronidazole. Gut 1982;23:1–7.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Loft S, Sonne J, Dossing M, Andreasen PB. Metronidazole pharmacokinetics in patients with hepatic encephalopathy. Scand J Gastroenterol 1987;22:117–123.PubMedCrossRefGoogle Scholar
  99. 99.
    Heredia D, Caballeria J, Arroyo V, Ravelli G, Rodes J. Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE). J Hepatol 1987;4:293–298.PubMedCrossRefGoogle Scholar
  100. 100.
    Mendenhall CL, Rouster S, Marshall L, Weesner R. A new therapy for portal systemic encephalopathy. Am J Gastroenterol 1986;81(7):540–543.PubMedGoogle Scholar
  101. 101.
    Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves hepatic encephalopathy: Results of a randomized controlled trial. Lancet 1984;493.Google Scholar
  102. 102.
    Singh HK, Gulati A, Srimal RC, Dhawan BN. Effect of Ro 15–1788 on dizepam, GABA and pentobarbitone induced EEG changes in rabbits. Indian J Med Res 1986;83:633–641.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Gerald Y. Minuk
    • 1
  1. 1.Department of MedicineUniversity of ManitobaWinnipegCanada

Personalised recommendations