About this Journal Submit a Manuscript Table of Contents
Gastroenterology Research and Practice
Volume 2012 (2012), Article ID 642108, 7 pages
http://dx.doi.org/10.1155/2012/642108
Review Article

Pathogenesis of Hepatic Encephalopathy

1Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, Sniadeckich Street 5, 31-531 Krakow, Poland
2Department of Neurology, Jagiellonian University Medical College, Sniadeckich Street 5, 31-531 Krakow, Poland

Received 14 October 2012; Revised 16 November 2012; Accepted 16 November 2012

Academic Editor: Sergio Morini

Copyright © 2012 Irena Ciećko-Michalska 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. P. Ferenci, A. Lockwood, K. Mullen, R. Tarter, K. Weissenborn, and A. T. Blei, “Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998,” Hepatology, vol. 35, no. 3, pp. 716–721, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. R. Prakash and K. D. Mullen, “Mechanisms, diagnosis and management of hepatic encephalopathy,” Nature Reviews Gastroenterology and Hepatology, vol. 7, no. 9, pp. 515–525, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Weissenborn, J. C. Ennen, H. Schomerus, N. Rückert, and H. Hecker, “Neuropsychological characterization of hepatic encephalopathy,” Journal of Hepatology, vol. 34, no. 5, pp. 768–773, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Duarte-Rojo, J. Estradas, R. Hernández-Ramos, S. Ponce-de-León, J. Córdoba, and A. Torre, “Validation of the Psychometric Hepatic Encephalopathy Score (PHES) for identifying patients with minimal hepatic encephalopathy,” Digestive Diseases and Sciences, vol. 56, no. 10, pp. 3014–3023, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. N. Gitlin, “Subclinical portal-systemic encephalopathy,” American Journal of Gastroenterology, vol. 83, no. 1, pp. 8–11, 1988. View at Scopus
  6. J. Y. Montgomery and J. S. Bajaj, “Advances in the evaluation and management of minimal hepatic encephalopathy,” Current Gastroenterology Reports, vol. 13, no. 1, pp. 26–33, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. F. F. Poordad, “Review article: the burden of hepatic encephalopathy,” Alimentary Pharmacology and Therapeutics, vol. 25, no. 1, pp. 3–9, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Das, R. K. Dhiman, V. A. Saraswat, M. Verma, and S. R. Naik, “Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis,” Journal of Gastroenterology and Hepatology, vol. 16, no. 5, pp. 531–535, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. J. C. Quero and S. W. Schalm, “Subclinical hepatic encephalopathy,” Seminars in Liver Disease, vol. 16, no. 3, pp. 321–328, 1996. View at Scopus
  10. M. Romero-Gómez, F. Boza, M. S. García-Valdecasas, E. García, and J. Aguilar-Reina, “Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy,” American Journal of Gastroenterology, vol. 96, no. 9, pp. 2718–2723, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Habior, E. Kraszewska, A. Goś-Zając et al., “Minimalna encefalopatia u chorych z marskością wątroby—ocena metod diagnostycznych i częstości występowania,” Postępy NaukMedycznych, vol. 11, pp. 769–778, 2008.
  12. D. Häussinger, “Hepatic encephalopathy,” Acta Gastro-Enterologica Belgica, vol. 73, no. 4, pp. 457–464, 2010. View at Scopus
  13. R. K. Dhiman, V. A. Saraswat, B. K. Sharma et al., “Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for Study of the Liver,” Journal of Gastroenterology and Hepatology, vol. 25, no. 6, pp. 1029–1041, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. P. Amodio, S. Montagnese, A. Gatta, and M. Y. Morgan, “Characteristics of minimal hepatic encephalopathy,” Metabolic Brain Disease, vol. 19, no. 3-4, pp. 253–267, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. O. Cauli, R. Rodrigo, M. Llansola et al., “Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy,” Metabolic Brain Disease, vol. 24, no. 1, pp. 69–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. V. Felipo, A. Urios, E. Montesinos et al., “Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy,” Metabolic Brain Disease, vol. 27, no. 1, pp. 51–58, 2012. View at Publisher · View at Google Scholar
  17. V. Felipo and R. F. Butterworth, “Neurobiology of ammonia,” Progress in Neurobiology, vol. 67, no. 4, pp. 259–279, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. N. J. Abbott, L. Rönnbäck, and E. Hansson, “Astrocyte-endothelial interactions at the blood-brain barrier,” Nature Reviews Neuroscience, vol. 7, no. 1, pp. 41–53, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. R. F. Butterworth, J. F. Giguère, J. Michaud, J. Lavoie, and G. P. Layrargues, “Ammonia: key factor in the pathogenesis of hepatic encephalopathy,” Neurochemical Pathology, vol. 6, no. 1-2, pp. 1–12, 1987. View at Publisher · View at Google Scholar · View at Scopus
  20. R. F. Butterworth, G. Girard, and J. F. Giguere, “Regional differences in the capacity for ammonia removal by brain following portocaval anastomosis,” Journal of Neurochemistry, vol. 51, no. 2, pp. 486–490, 1988. View at Scopus
  21. D. Haussinger, “Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureogenesis in perfused rat liver,” European Journal of Biochemistry, vol. 133, no. 2, pp. 269–275, 1983. View at Scopus
  22. M. D. Norenberg and A. Martinez-Hernandez, “Fine structural localization of glutamine synthetase in astrocytes of rat brain,” Brain Research, vol. 161, no. 2, pp. 303–310, 1979. View at Publisher · View at Google Scholar · View at Scopus
  23. A. T. Blei, S. Olafsson, G. Therrien, and R. F. Butterworth, “Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis,” Hepatology, vol. 19, no. 6, pp. 1437–1444, 1994. View at Publisher · View at Google Scholar · View at Scopus
  24. S. W. Brusilow, R. C. Koehler, R. J. Traystman, and A. J. L. Cooper, “Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy,” Neurotherapeutics, vol. 7, no. 4, pp. 452–470, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Skowrońska and J. Albrecht, “Alterations of blood brain barrier function in hyperammonemia: an overview,” Neurotoxicity Research, vol. 21, no. 2, pp. 236–244, 2012. View at Publisher · View at Google Scholar
  26. A. Srivastava, S. K. Yadav, S. K. Yachha, M. A. Thomas, V. A. Saraswat, and R. K. Gupta, “Pro-inflammatory cytokines are raised in extrahepatic portal venous obstruction, with minimal hepatic encephalopathy,” Journal of Gastroenterology and Hepatology, vol. 26, no. 6, pp. 979–986, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. T. Li, X. Li, W. Zhou, X. Cui, and L. Ma, “Dynamic susceptibility contrast-enhanced first-pass perfusion MR imaging in patients with subclinical hepatic encephalopathy,” Journal of Neuroradiology, vol. 39, no. 5, pp. 290–294, 2012. View at Publisher · View at Google Scholar
  28. N. J. Abbott and I. A. Romero, “Transporting therapeutics across the blood-brain barrier,” Molecular Medicine Today, vol. 2, no. 3, pp. 106–113, 1996. View at Publisher · View at Google Scholar · View at Scopus
  29. N. J. Abbott, “Astrocyte-endothelial interactions and blood-brain barrier permeability,” Journal of Anatomy, vol. 200, no. 6, pp. 629–638, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiology of Disease, vol. 37, no. 1, pp. 13–25, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Wolburg and A. Lippoldt, “Tight junctions of the blood-brain barrier: development, composition and regulation,” Vascular Pharmacology, vol. 38, no. 6, pp. 323–337, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. N. J. Abbott, “Dynamics of CNS barriers: evolution, differentiation, and modulation,” Cellular and Molecular Neurobiology, vol. 25, no. 1, pp. 5–23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. M. D. Norenberg and A. S. Bender, “Astrocyte swelling in liver failure: role of glutamine and benzodiazepines,” Acta Neurochirurgica, vol. 60, pp. 24–27, 1994. View at Scopus
  34. J. O. Clemmesen, F. S. Larsen, J. Kondrup, B. A. Hansen, and P. Ott, “Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration,” Hepatology, vol. 29, no. 3, pp. 648–653, 1999. View at Scopus
  35. P. Desjardins, T. Du, W. Jiang, L. Peng, and R. F. Butterworth, “Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure: role of glutamine redefined,” Neurochemistry International, vol. 60, no. 7, pp. 690–696, 2012. View at Publisher · View at Google Scholar
  36. G. Wright, N. A. Davies, D. L. Shawcross et al., “Endotoxemia produces coma and brain swelling in bile duct ligated rats,” Hepatology, vol. 45, no. 6, pp. 1517–1526, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Wright, Y. Sharifi, and R. Jalan, “Blood-brain barrier in liver failure: are cracks appearing in the wall?” Liver International, vol. 30, no. 8, pp. 1087–1090, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. M. E. Horowitz, D. F. Schafer, P. Molnar, et al., “Increased blood-brain transfer in a rabbit model of acute liver failure,” Gastroenterology, vol. 84, no. 5, part 1, pp. 1003–1011, 1983. View at Scopus
  39. J. H. Nguyen, S. Yamamoto, J. Steers et al., “Matrix metalloproteinase-9 contributes to brain extravasation and edema in fulminant hepatic failure mice,” Journal of Hepatology, vol. 44, no. 6, pp. 1105–1114, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. L. Chavarria, M. Oria, J. Romero-Gimenez, J. Alonso, S. Lope-Piedrafita, and J. Cordoba, “Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure,” Gastroenterology, vol. 138, no. 4, pp. 1566–1573, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. K. Sawara, P. Desjardins, N. Chatauret, A. Kato, K. Suzuki, and R. F. Butterworth, “Alterations in expression of genes coding for proteins of the neurovascular unit in ischemic liver failure,” Neurochemistry International, vol. 55, no. 1–3, pp. 119–123, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. O. Cauli, P. Lpezlarrubia, R. Rodrigo et al., “Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats,” Gastroenterology, vol. 140, no. 2, pp. 638–645, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Lv, H. L. Song, Y. Zhou et al., “Tumour necrosis factor-α affects blood-brain barrier permeability and tight junction-associated occludin in acute liver failure,” Liver International, vol. 30, no. 8, pp. 1198–1210, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. F. Tofteng and F. S. Larsen, “Monitoring extracellular concentrations of lactate, glutamate, and glycerol by in vivo microdialysis in the brain during liver transplantation in acute liver failure,” Liver Transplantation, vol. 8, no. 3, pp. 302–305, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Kato, R. D. Hughes, R. T. Keays, and R. Williams, “Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure,” Hepatology, vol. 15, no. 6, pp. 1060–1066, 1992. View at Publisher · View at Google Scholar · View at Scopus
  46. R. Kumar, Shalimar, and H. Sharma, “Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure,” Clinical Gastroenterology and Hepatology, vol. 10, no. 8, pp. 925–931, 2012.
  47. J. Albrecht and E. A. Jones, “Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome,” Journal of the Neurological Sciences, vol. 170, no. 2, pp. 138–146, 1999. View at Scopus
  48. K. D. Mullen, K. M. Szauter, and K. Kaminsky-Russ, “'Endogenous' benzodiazepine activity in body fluids of patients with hepatic encephalopathy,” The Lancet, vol. 336, no. 8707, pp. 81–83, 1990. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Goulenok, B. Bernard, J. F. Cadranel et al., “Flumazenil versus placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis,” Alimentary Pharmacology and Therapeutics, vol. 16, no. 3, pp. 361–372, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. M. D. Norenberg, “Astroglial dysfunction in hepatic encephalopathy,” Metabolic Brain Disease, vol. 13, no. 4, pp. 319–335, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. Y. Itzhak and M. D. Norenberg, “Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [3H]PK 11195,” Neuroscience Letters, vol. 177, no. 1-2, pp. 35–38, 1994. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Itzhak, A. Roig-Cantisano, R. S. Dombro, and M. D. Norenberg, “Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain,” Brain Research, vol. 705, no. 1-2, pp. 345–348, 1995. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Ahboucha, G. P. Layrargues, O. Mamer, and R. F. Butterworth, “Increased brain concentrations of a neuroinhibitory steroid in human hepatic encephalopathy,” Annals of Neurology, vol. 58, no. 1, pp. 169–170, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Ahboucha, G. Talani, T. Fanutza et al., “Reduced brain levels of DHEAS in hepatic coma patients: significance for increased GABAergic tone in hepatic encephalopathy,” Neurochemistry International, vol. 61, no. 1, pp. 48–53, 2012. View at Publisher · View at Google Scholar
  55. O. Cauli, M. Llansola, S. Erceg, and V. Felipo, “Hypolocomotion in rats with chronic liver failure is due to increased glutamate and activation of metabotropic glutamate receptors in substantia nigra,” Journal of Hepatology, vol. 45, no. 5, pp. 654–661, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Groeneweg, J. C. Quero, I. de Bruijn et al., “Subclinical hepatic encephalopathy impairs daily functioning,” Hepatology, vol. 28, no. 1, pp. 45–49, 1998. View at Publisher · View at Google Scholar · View at Scopus
  57. A. P. Sinke, A. R. Jayakumar, K. S. Panickar, M. Moriyama, P. V. B. Reddy, and M. D. Norenberg, “NFκB in the mechanism of ammonia-induced astrocyte swelling in culture,” Journal of Neurochemistry, vol. 106, no. 6, pp. 2302–2311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. M. D. Norenberg, A. R. Jayakumar, K. V. Rama Rao, and K. S. Panickar, “New concepts in the mechanism of ammonia-induced astrocyte swelling,” Metabolic Brain Disease, vol. 22, no. 3-4, pp. 219–234, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Häussinger, F. Schliess, and G. Kircheis, “Pathogenesis of hepatic encephalopathy,” Journal of Gastroenterology and Hepatology, vol. 17, no. 3, pp. S256–S259, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Mardini, F. E. Smith, C. O. Record, and A. M. Blamire, “Magnetic resonance quantification of water and metabolites in the brain of cirrhotics following induced hyperammonaemia,” Journal of Hepatology, vol. 54, no. 6, pp. 1154–1160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. R. García-Martínez and J. Córdoba, “Acute-on-chronic liver failure: the brain,” Current Opinion in Critical Care, vol. 17, no. 2, pp. 177–183, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. 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 · View at Scopus
  63. D. L. Shawcross, G. Wright, S. W. M. Olde Damink, and R. Jalan, “Role of ammonia and inflammation in minimal hepatic encephalopathy,” Metabolic Brain Disease, vol. 22, no. 1, pp. 125–138, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. V. M. Alvarez, K. V. Rama Rao, M. Brahmbhatt, and M. D. Norenberg, “Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes,” Journal of Neuroscience Research, vol. 89, no. 12, pp. 2028–2040, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. K. V. Rama Rao and M. D. Norenberg, “Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy,” Neurochemistry International, vol. 60, no. 7, pp. 697–706, 2012. View at Publisher · View at Google Scholar
  66. K. V. Rama Rao, A. R. Jayakumar, and M. D. Norenberg, “Ammonia neurotoxicity: role of the mitochondrial permeability transition,” Metabolic Brain Disease, vol. 18, no. 2, pp. 113–127, 2003. View at Publisher · View at Google Scholar · View at Scopus
  67. K. V. Rao and M. D. Norenberg, “Cerebral energy metabolism in Hepatic Encephalopathy and hyperammonemia,” Metabolic Brain Disease, vol. 16, no. 1-2, pp. 67–78, 2001. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Zwingmann and R. Butterworth, “An update on the role of brain glutamine synthesis and its relation to cell-specific energy metabolism in the hyperammonemic brain: further studies using NMR spectroscopy,” Neurochemistry International, vol. 47, no. 1-2, pp. 19–30, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Chen and R. A. Swanson, “Astrocytes and brain injury,” Journal of Cerebral Blood Flow and Metabolism, vol. 23, no. 2, pp. 137–149, 2003. View at Scopus
  70. M. D. Norenberg, “The role of astrocytes in hepatic encephalopathy,” Neurochemical Pathology, vol. 6, no. 1-2, pp. 13–33, 1987. View at Publisher · View at Google Scholar · View at Scopus
  71. R. F. Butterworth, “Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy,” Neurochemistry International, vol. 57, no. 4, pp. 383–388, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. M. D. Norenberg, “A light and electron microscopic study of experimental portal systemic (ammonia) encephalopathy. Progression and reversal of the disorder,” Laboratory Investigation, vol. 36, no. 6, pp. 618–627, 1977. View at Scopus
  73. L. Sokoloff, “Relation between physiological function and energy metabolism in the central nervous system,” Journal of Neurochemistry, vol. 29, no. 1, pp. 13–26, 1977. View at Scopus
  74. A. H. Lockwood, E. W. H. Yap, and W. H. Wong, “Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy,” Journal of Cerebral Blood Flow and Metabolism, vol. 11, no. 2, pp. 337–341, 1991. View at Scopus
  75. K. Weissenborn, M. Bokemeyer, B. Ahl et al., “Functional imaging of the brain in patients with liver cirrhosis,” Metabolic Brain Disease, vol. 19, no. 3-4, pp. 269–280, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. Y. Yazgan, Y. Narin, L. Demirturk et al., “Value of regional cerebral blood flow in the evaluation of chronic liver disease and subclinical hepatic encephalopathy,” Journal of Gastroenterology and Hepatology, vol. 18, no. 10, pp. 1162–1167, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. G. Pomier-Layrargues, L. Spahr, and R. F. Butterworth, “Increased manganese concentrations in pallidum of cirrhotic patients,” The Lancet, vol. 345, no. 8951, p. 735, 1995. View at Scopus
  78. D. Krieger, S. Krieger, O. Jansen, P. Gass, L. Theilmann, and H. Lichtnecker, “Manganese and chronic hepatic encephalopathy,” The Lancet, vol. 346, no. 8970, pp. 270–274, 1995. View at Scopus
  79. G. P. Layrargues, D. Shapcott, L. Spahr, and R. F. Butterworth, “Accumulation of manganese and copper in pallidum of cirrhotic patients: role in the pathogenesis of hepatic encephalopathy?” Metabolic Brain Disease, vol. 10, no. 4, pp. 353–356, 1995. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Spahr, R. F. Butterworth, S. Fontaine et al., “Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms,” Hepatology, vol. 24, no. 5, pp. 1116–1120, 1996. View at Publisher · View at Google Scholar · View at Scopus
  81. R. E. Tarter, S. L. Sandford, A. L. Hays, J. P. Carra, and D. H. van Thiel, “Hepatic injury correlates with neuropsychologic impairment,” International Journal of Neuroscience, vol. 44, no. 1-2, pp. 75–82, 1989. View at Scopus
  82. R. E. Tarter, A. M. Hegedus, and D. H. van Thiel, “Nonalcoholic cirrhosis associated with neuropsychological dysfunction in the absence of overt evidence of hepatic encephalopathy,” Gastroenterology, vol. 86, no. 6, pp. 1421–1427, 1984. View at Scopus
  83. R. K. Dhiman and Y. K. Chawla, “Minimal hepatic encephalopathy,” Indian Journal of Gastroenterology, vol. 28, no. 1, pp. 5–16, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Kulisevsky, J. Pujol, C. Junque, J. Deus, J. Balanzó, and A. Capdevila, “MRI pallidal hyperintensity and brain atrophy in cirrhotic patients: two different MRI patterns of clinical deterioration?” Neurology, vol. 43, no. 12, pp. 2570–2573, 1993. View at Scopus
  85. E. E. Powell, M. P. Pender, J. B. Chalk et al., “Improvement in chronic hepatocerebral degeneration following liver transplantation,” Gastroenterology, vol. 98, no. 4, pp. 1079–1082, 1990. View at Scopus
  86. A. Gupta, R. K. Dhiman, S. Kumari et al., “Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy,” Journal of Hepatology, vol. 53, no. 5, pp. 849–855, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. D. W. Jun, K. T. Kim, O. Y. Lee et al., “Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients,” Digestive Diseases and Sciences, vol. 55, no. 5, pp. 1465–1471, 2010. View at Publisher · View at Google Scholar · View at Scopus