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Journal of Clinical and Experimental Hepatology logoLink to Journal of Clinical and Experimental Hepatology
. 2011 Nov 9;1(2):77–86. doi: 10.1016/S0973-6883(11)60126-6

Pathogenesis, Diagnosis, and Treatment of Hepatic Encephalopathy

Dileep K Atluri 1, Ravi Prakash 1, Kevin D Mullen 1,*
PMCID: PMC3940085  PMID: 25755319

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician.

Keywords: Diagnosis, hepatic encephalopathy, pathogenesis, treatment

Abbreviations: AAA, aromatic amino acid; BAUR, brain ammonia utilization rate; BCAA, branched-chain amino acids; CFF, critical flicker fusion; DBI, diazepam binding inhibitor; DST, digit symbol test; DWI, diffusion weighted imaging; ECAD, extra-corporeal albumin dialysis; EEC, electroencephalogram; FLAIR, fluid attenuation inversion recovery; HE, hepatic encephalopathy; HESA, hepatic encephalopathy scoring algorithm; ICT, inhibitory control test; IL, interleukin; LOLA, L-ornithine L-aspartate; LTT, line tracing test; MARS, molecular adsorbent reticulating system; MHE, minimal hepatic encephalopathy; MRI, magnetic resonance imaging; NAC, N-acetyl cysteine; NO, nitric oxide; NS, neurosteroids; NSAID, non-steroidal anti-inflammatory drugs; ODN, octadecaneuropeptide; OHE, overt hepatic encephalopathy; PTBR, peripheral-type benzodiaze-pine receptor; QOL, quality of life; SDT, serial dotting test; SEDACA, short epoch, dominant activity, and cluster analysis; SIBO, small intestinal bacterial overgrowth; SIRS, systemic inflammatory response syndrome; SOD, Superoxide dismutase; SONIC, spectrum of neurological impairment; TLP, TransLocator Protein; TNF, tumor necrosis factor

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References

  • 1.Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy-definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716–721. doi: 10.1053/jhep.2002.31250. [DOI] [PubMed] [Google Scholar]
  • 2.Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50:2014–2021. doi: 10.1002/hep.23216. [DOI] [PubMed] [Google Scholar]
  • 3.Bajaj JS, Cordoba J, Mullen KD. Review article: the design of clinical trials in hepatic encephalopathy-an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther. 2011;33:739–747. doi: 10.1111/j.1365-2036.2011.04590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Bajaj JS, Saeian K, Schubert CM. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology. 2009;50:1175–1183. doi: 10.1002/hep.23128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Groeneweg M, Quero JC, De Bruijn I. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology. 1998;28:45–49. doi: 10.1002/hep.510280108. [DOI] [PubMed] [Google Scholar]
  • 6.Adams RD, Foley JM. The neurological disorder associated with liver disease. Proc Assoc Res Nerv Ment Dis. 1953;32:198–237. [PubMed] [Google Scholar]
  • 7.Nencki M, Zaleski J. On the quantitation of ammonia in animal fluids and tissues Naunyn Schmiedebergs. Arch Exp Pathol Pharmakol. 1895;36:385–396. [Google Scholar]
  • 8.Nencki M, Pawlow J, Zaleski J. On the content of ammonia in blood within organs and on formation of urea in mammals. Naunyn Schmiedebergs. Arch Exp Pathol Pharmakol. 1896;37:26–51. [Google Scholar]
  • 9.Ehrlich M, Plum F, Duffy TE. Blood and brain ammonia concentrations after portacaval anastomosis. Effects of acute ammonia loading. J Neurochem. 1980;34:1538–1542. doi: 10.1111/j.1471-4159.1980.tb11238.x. [DOI] [PubMed] [Google Scholar]
  • 10.Lockwood AH, McDonald JM, Reiman RE. The dynamics of ammonia metabolism in man. Effects of liver disease and hyper-ammonemia. J Clin Invest. 1979;63:449–460. doi: 10.1172/JCI109322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Lockwood AH, Yap EW, Wong WH. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J Cereb Blood Flow Metab. 1991;11:337–341. doi: 10.1038/jcbfm.1991.67. [DOI] [PubMed] [Google Scholar]
  • 12.Szerb JC, Butterworth RF. Effect of ammonium ions on synaptic transmission in the mammalian central nervous system. Prog Neurobiol. 1992;39:135–153. doi: 10.1016/0301-0082(92)90008-3. [DOI] [PubMed] [Google Scholar]
  • 13.Hindfelt B, Plum F, Duffy TE. Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest. 1977;59:386–396. doi: 10.1172/JCI108651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Larsen FS, Strauss G, Moller K, Hansen BA. Regional cerebral blood flow autoregulation in patients with fulminant hepatic failure. Liver Transpl. 2000;6:795–800. doi: 10.1053/jlts.2000.18705. [DOI] [PubMed] [Google Scholar]
  • 15.Vaquero J, Polson J, Chung C. Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology. 2003;125:755–764. doi: 10.1016/s0016-5085(03)01051-5. [DOI] [PubMed] [Google Scholar]
  • 16.Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40:247–254. doi: 10.1016/j.jhep.2003.10.016. [DOI] [PubMed] [Google Scholar]
  • 17.Shawcross DL, Wright G, Olde Damink SW, Jalan R. Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis. 2007;22:125–138. doi: 10.1007/s11011-006-9042-1. [DOI] [PubMed] [Google Scholar]
  • 18.Sharifi Y, Yeoman A, Austin M. Defining the outcomes of severe hepatic encephalopathy in cirrhosis: inflammation is the key. Hepatology. 2008;48(Suppl):1061A. [Google Scholar]
  • 19.Licinio J, Wong ML. Pathways and mechanisms for cytokine signaling of the central nervous system. J Clin Invest. 1997;100:2941–2947. doi: 10.1172/JCI119846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Shawcross DL, Shabbir SS, Taylor NJ, Hughes RD. Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology. 2010;51:1062–1069. doi: 10.1002/hep.23367. [DOI] [PubMed] [Google Scholar]
  • 21.Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology. 2007;46:514–519. doi: 10.1002/hep.21734. [DOI] [PubMed] [Google Scholar]
  • 22.Shawcross DL, Sharifi Y, Canavan JB. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol. 2011;54:640–649. doi: 10.1016/j.jhep.2010.07.045. [DOI] [PubMed] [Google Scholar]
  • 23.Bemeur C, Desjardins P, Butterworth RF. Evidence for oxidative/nitrosative stress in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2010;25:3–9. doi: 10.1007/s11011-010-9177-y. [DOI] [PubMed] [Google Scholar]
  • 24.Ahboucha S, Butterworth RF. The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem Int. 2008;52:575–587. doi: 10.1016/j.neuint.2007.05.004. [DOI] [PubMed] [Google Scholar]
  • 25.Atluri DK, Asgeri M, Mullen KD. Reversibility of hepatic encephalopathy after liver transplantation. Metab Brain Dis. 2010;25:111–113. doi: 10.1007/s11011-010-9178-x. [DOI] [PubMed] [Google Scholar]
  • 26.Ong JP, Aggarwal A, Krieger D. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003;114:188–193. doi: 10.1016/s0002-9343(02)01477-8. [DOI] [PubMed] [Google Scholar]
  • 27.Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol. 2010;7:515–525. doi: 10.1038/nrgastro.2010.116. [DOI] [PubMed] [Google Scholar]
  • 28.Conn HO, Leevy CM, Vlahcevic ZR. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977;72(4 Pt 1):573–583. [PubMed] [Google Scholar]
  • 29.Haussinger D, Cordoba Cardona J, Kircheis G. Definition and assessment of low-grade hepatic encephalopathy. In: Haussinger D, Kircheis G, Schliess F, editors. Hepatic Encephalopathy and Nitrogen Metabolism. Springer-Verlag; Netherlands: 2006. pp. 423–432. [Google Scholar]
  • 30.Kircheis G, Fleig WE, Gortelmeyer R, Grafe S, Haussinger D. Assessment of low-grade hepatic encephalopathy: a critical analysis. J Hepatol. 2007;47:642–650. doi: 10.1016/j.jhep.2007.05.019. [DOI] [PubMed] [Google Scholar]
  • 31.Hassanein TI, Hilsabeck RC, Perry W. Introduction to the hepatic encephalopathy scoring algorithm (HESA) Dig Dis Sci. 2008;53:529–538. doi: 10.1007/s10620-007-9895-0. [DOI] [PubMed] [Google Scholar]
  • 32.Hassanein T, Blei AT, Perry W. Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy. Am J Gastroenterol. 2009;104:1392–1400. doi: 10.1038/ajg.2009.160. [DOI] [PubMed] [Google Scholar]
  • 33.Ortiz M, Cordoba J, Doval E. Development of a clinical hepatic encephalopathy staging scale. Aliment Pharmacol Ther. 2007;26:859–867. doi: 10.1111/j.1365-2036.2007.03394.x. [DOI] [PubMed] [Google Scholar]
  • 34.Weissenborn K, Ennen JC, Schomerus H, Ruckert N, Hecker H. Neuropsychological characterization of hepatic encephalopathy. J Hepatol. 2001;34:768–773. doi: 10.1016/s0168-8278(01)00026-5. [DOI] [PubMed] [Google Scholar]
  • 35.Randolph C, Hilsabeck R, Kato A. Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver Int. 2009;29:629–635. doi: 10.1111/j.1478-3231.2009.02009.x. [DOI] [PubMed] [Google Scholar]
  • 36.Iduru S, Mullen KD. The demise of the pencil? New computer-assisted tests for minimal hepatic encephalopathy. Gastroenterology. 2008;135:1455–1456. doi: 10.1053/j.gastro.2008.09.040. [DOI] [PubMed] [Google Scholar]
  • 37.Bajaj JS, Saeian K, Verber MD. Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy. Am J Gastroenterol. 2007;102:754–760. doi: 10.1111/j.1572-0241.2007.01048.x. [DOI] [PubMed] [Google Scholar]
  • 38.Bajaj JS, Hafeezullah M, Franco J. Inhibitory control test for the diagnosis of minimaI hepatic encephalopathy. Gastroenterology. 2008;135:1591. doi: 10.1053/j.gastro.2008.07.021. 600e1. [DOI] [PubMed] [Google Scholar]
  • 39.Mardini H, Saxby BK, Record CO. Computerized psychometric testing in minimal encephalopathy and modulation by nitrogen challenge and liver transplant. Gastroenterology. 2008;135:1582–1590. doi: 10.1053/j.gastro.2008.06.043. [DOI] [PubMed] [Google Scholar]
  • 40.Kircheis G, Wettstein M, Timmermann L, Schnitzler A, Haussinger D. Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology. 2002;35:357–366. doi: 10.1053/jhep.2002.30957. [DOI] [PubMed] [Google Scholar]
  • 41.Kircheis G, Bode JG, Hilger N, Kramer T, Schnitzler A, Haussinger D. Diagnostic and prognostic values of critical flicker frequency determination as new diagnostic tool for objective HE evaluation in patients undergoing TIPS implantation. EurJ Gastroenterol Hepatol. 2009;21:1383–1394. doi: 10.1097/MEG.0b013e328310e0c3. [DOI] [PubMed] [Google Scholar]
  • 42.Bahamon-Dussan JE, Celesia GG, Grigg-Damberger MM. Prognostic significance of EEG triphasic waves in patients with altered state of consciousness. J Clin Neurophysiol. 1989;6:313–319. doi: 10.1097/00004691-198910000-00002. [DOI] [PubMed] [Google Scholar]
  • 43.Montagnese S, Jackson C, Morgan MY. Spatio-temporal decomposition of the electroencephalogram in patients with cirrhosis. J Hepatol. 2007;46:447–458. doi: 10.1016/j.jhep.2006.10.015. [DOI] [PubMed] [Google Scholar]
  • 44.Amodio P, Pellegrini A, Ubiali E. The EEG assessment of low-grade hepatic encephalopathy: comparison of an artificial neural network-expert system (ANNES) based evaluation with visual EEG readings and EEG spectral analysis. Clin Neurophysiol. 2006;117:2243–2251. doi: 10.1016/j.clinph.2006.06.714. [DOI] [PubMed] [Google Scholar]
  • 45.Cordoba J, Sanpedro F, Alonso J, Rovira A. 1H magnetic resonance in the study of hepatic encephalopathy in humans. Metab Brain D/s. 2002;17:415–429. doi: 10.1023/a:1021926405944. [DOI] [PubMed] [Google Scholar]
  • 46.Rovira A, Alonso J, Cordoba J. MR imaging findings in hepatic encephalopathy. AJNRAm J Neuroradiol. 2008;29:1612–1621. doi: 10.3174/ajnr.A1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Conn H, Lieberthal M. The Hepatic Coma Syndromes and Lactulose. Williams and Wilkins; Baltimore: 1979. [Google Scholar]
  • 48.van Leeuwen PA, van Berlo CL, Soeters PB. New mode of action for lactulose. Lancet. 1988;1:55–56. doi: 10.1016/s0140-6736(88)91033-1. [DOI] [PubMed] [Google Scholar]
  • 49.Camma C, Fiorello F, Tine F, Marchesini G, Fabbri A, Pagliaro L. Lactitol in treatment of acute hepatic encephalopathy. A meta-analysis. Dig Dis Sci. 1993;38:916–922. doi: 10.1007/BF01295920. [DOI] [PubMed] [Google Scholar]
  • 50.Uribe M, Campollo O, Vargas F. Acidifying enemas (lactitol and lactose) vs nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial. Hepatology. 1987;7:639–643. doi: 10.1002/hep.1840070404. [DOI] [PubMed] [Google Scholar]
  • 51.Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. BMJ. 2004;328:1046. doi: 10.1136/bmj.38048.506134.EE. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Cordoba J, Minguez B, Vergara M. Treatment of hepatic encephalopathy. Lancet. 2005;365:1384–1385. doi: 10.1016/S0140-6736(05)66366-0. author reply 5-6. [DOI] [PubMed] [Google Scholar]
  • 53.Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007;45:549–559. doi: 10.1002/hep.21533. [DOI] [PubMed] [Google Scholar]
  • 54.Strauss E, Tramáte R, Silva EP. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology. 1992;39:542–545. [PubMed] [Google Scholar]
  • 55.Mas A, Rodes J, Sunyer L. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38:51–58. doi: 10.1016/s0168-8278(02)00350-1. [DOI] [PubMed] [Google Scholar]
  • 56.Pedretti G, Calzetti C, Missale G, Fiaccadori F. Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial. Ital J Gastroenterol. 1991;23:175–178. [PubMed] [Google Scholar]
  • 57.Bass NM, Mullen KD, Sanyal A. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071–1081. doi: 10.1056/NEJMoa0907893. [DOI] [PubMed] [Google Scholar]
  • 58.Mullen K, Prakash R. Rifaximin for the treatment of hepatic encephalopathy. Expert Rev Gastroenterol Hepatol. 2010;4:665–677. doi: 10.1586/egh.10.78. [DOI] [PubMed] [Google Scholar]
  • 59.Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982;23:1–7. doi: 10.1136/gut.23.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Basu AP, Rayapudi K, Estevez J, Brown RS. A pilot study utilizing nitazoxanide for hepatic encephalopathy in Chronic Liver Disease Program and Abstracts of the 59th Annual Meeting of the American Association for the Study of Liver Diseases (Abstract). 2008(October 31-November 4):1742.
  • 61.Holecek M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition. 2010;26:482–490. doi: 10.1016/j.nut.2009.06.027. [DOI] [PubMed] [Google Scholar]
  • 62.Les I, Doval E, Garcia-Martinez R. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol. 2011;106:1081–1088. doi: 10.1038/ajg.2011.9. [DOI] [PubMed] [Google Scholar]
  • 63.Ndraha S, Hasan I, Simadibrata M. The effect of L-ornithine L-aspartate and branch chain amino acids on encephalopathy and nutritional status in liver cirrhosis with malnutrition. Acta Med Indones. 2011;43:18–22. [PubMed] [Google Scholar]
  • 64.Naylor CD, O'Rourke K, Detsky AS, Baker JP. Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy. A meta-analysis. Gastroenterology. 1989;97:1033–1042. doi: 10.1016/0016-5085(89)91517-5. [DOI] [PubMed] [Google Scholar]
  • 65.Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev. 2003 doi: 10.1002/14651858.CD001939. CD001939. [DOI] [PubMed] [Google Scholar]
  • 66.Rose C, Michalak A, Pannunzio P. L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis. 1998;13:147–157. doi: 10.1023/a:1020613314572. [DOI] [PubMed] [Google Scholar]
  • 67.Kircheis G, Nilius R, Held C. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology. 1997;25:1351–1360. doi: 10.1002/hep.510250609. [DOI] [PubMed] [Google Scholar]
  • 68.Stauch S, Kircheis G, Adler G. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol. 1998;28:856–864. doi: 10.1016/s0168-8278(98)80237-7. [DOI] [PubMed] [Google Scholar]
  • 69.Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet. 1984;2:493–495. doi: 10.1016/s0140-6736(84)92567-4. [DOI] [PubMed] [Google Scholar]
  • 70.Marshall AW, Jakobovits AW, Morgan MY. Bromocriptine-associated hyponatraemia in cirrhosis. Br Med J (Clin Res Ed) 1982;285:1534–1535. doi: 10.1136/bmj.285.6354.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16:138–144. doi: 10.1002/hep.1840160123. [DOI] [PubMed] [Google Scholar]
  • 72.Als-Nielsen B, Gluud LL, Gluud C. Benzodiazepine receptor antagonists for hepatic encephalopathy. Cochrane Database Syst Rev. 2004 doi: 10.1002/14651858.CD002798.pub2. CD002798. [DOI] [PubMed] [Google Scholar]
  • 73.Loguercio C, Abbiati R, Rinaldi M, Romano A, Del Vecchio Blanco C, Coltorti M. Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J Hepatol. 1995;23:39–46. doi: 10.1016/0168-8278(95)80309-2. [DOI] [PubMed] [Google Scholar]
  • 74.Cordoba J, Lopez-Hellin J, Planas M. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41:38–43. doi: 10.1016/j.jhep.2004.03.023. [DOI] [PubMed] [Google Scholar]
  • 75.Bianchi GP, Marchesini G, Fabbri A. Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison. J Intern Med. 1993;233:385–392. doi: 10.1111/j.1365-2796.1993.tb00689.x. [DOI] [PubMed] [Google Scholar]
  • 76.Bajaj JS. Minimal hepatic encephalopathy matters in daily life. World J Gastroenterol. 2008;14:3609–3615. doi: 10.3748/wjg.14.3609. 21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Schmid M, Peck-Radosavljevic M, Konig F, Mittermaier C, Gangl A, Ferenci P. A double-blind, randomized, placebo-controlled trial of intravenous L-ornithine-L-aspartate on postural control in patients with cirrhosis. Liver Int. 2010;30:574–582. doi: 10.1111/j.1478-3231.2010.02213.x. [DOI] [PubMed] [Google Scholar]
  • 78.Bajaj JS, Saeian K, Christensen KM. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol. 2008;103:1707–1715. doi: 10.1111/j.1572-0241.2008.01861.x. [DOI] [PubMed] [Google Scholar]
  • 79.Sidhu SS, Goyal O, Mishra BP, Sood A, Chhina RS, Soni RK. Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial) Am J Gastroenterol. 2011;106:307–316. doi: 10.1038/ajg.2010.455. [DOI] [PubMed] [Google Scholar]
  • 80.Seyan AS, Hughes RD, Shawcross DL. Changing face of hepatic encephalopathy: role of inflammation and oxidative stress. World J Gastroenterol. 2010;16:3347–3357. doi: 10.3748/wjg.v16.i27.3347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Gupta A, Dhiman RK, Kumari S. Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. J Hepatol. 2010;53:49–55. doi: 10.1016/j.jhep.2010.05.017. [Epub 2010 Jul 17.] [DOI] [PubMed] [Google Scholar]

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