Evaluation and management of hepatic encephalopathy: Current status and future directions

Gut and Liver

Volumn 10, Issue 4, 2016, Pages 509-519

  Suraweera, Duminda ^a   Sundaram, Vinay ^b   Saab, Sammy ^c,d  

^a OLIVE VIEW UCLA MEDICAL CENTER   (United States)

^b CEDARS SINAI MEDICAL CENTER   (United States)

^c UCLA MEDICAL CENTER   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Hepatic encephalopathy; Liver cirrhosis; Liver diseases; Minimal hepatic encephalopathy

Indexed keywords

FLUMAZENIL; GLYCEROL PHENYLBUTYRATE; LACTITOL; LACTULOSE; MACROGOL; METRONIDAZOLE; NEOMYCIN; ORNITHINE ASPARTATE; PLACEBO; PROBIOTIC AGENT; RIFAXIMIN; VANCOMYCIN; ZINC; ANTIINFECTIVE AGENT; DISACCHARIDE;

CALORIC INTAKE; CAREGIVER BURDEN; CLINICAL EVALUATION; CLINICAL FEATURE; COMPUTER ASSISTED RADIOGRAPHY; DISEASE SEVERITY; DRUG EFFICACY; HEALTH CARE UTILIZATION; HEPATIC ENCEPHALOPATHY; HUMAN; LIVER GRAFT; LIVER INJURY; LIVER SUPPORT; NEUROPSYCHOLOGICAL TEST; PATHOGENESIS; PORTOSYSTEMIC ANASTOMOSIS; PROTEIN INTAKE; PSYCHOMETRY; QUALITY OF LIFE; REVIEW; SENSITIVITY AND SPECIFICITY; COMPLICATION; COST OF ILLNESS; FORECASTING; PATIENT ATTITUDE;

ANTI-BACTERIAL AGENTS; COST OF ILLNESS; DISACCHARIDES; FORECASTING; HEPATIC ENCEPHALOPATHY; HUMANS; PATIENT ACCEPTANCE OF HEALTH CARE;

EID: 84978537580     PISSN: 19762283     EISSN: None     Source Type: Journal    
DOI: 10.5009/gnl15419     Document Type: Review

References (100)

1. Stepanova M, Mishra A, Venkatesan C, Younossi ZM. In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol 2012;10:1034-1041.e1.
2. Parekh PJ, Balart LA. Ammonia and its role in the pathogenesis of hepatic encephalopathy. Clin Liver Dis 2015;19:529-537.
3. Poh Z, Chang PE. A current review of the diagnostic and treatment strategies of hepatic encephalopathy. Int J Hepatol 2012;2012:480309.
4. Brusilow SW. Hyperammonemic encephalopathy. Medicine (Baltimore) 2002;81:240-249.
5. Häussinger D, Kircheis G, Fischer R, Schliess F, vom Dahl S. Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema? J Hepatol 2000;32:1035-1038.
6. Zhang XD, Zhang LJ, Wu SY, Lu GM. Multimodality magnetic resonance imaging in hepatic encephalopathy: an update. World J Gastroenterol 2014;20:11262-11272.
7. Häussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008;57:1156-1165.
8. Reinehr R, Görg B, Becker S, et al. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 2007;55:758-771.
9. Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 2006;44:788-794.
10. Görg B, Qvartskhava N, Bidmon HJ, et al. Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. Hepatology 2010;52:256-265.
11. Ahboucha S, Talani G, Fanutza T, et al. Reduced brain levels of DHEAS in hepatic coma patients: significance for increased GABAergic tone in hepatic encephalopathy. Neurochem Int 2012;61:48-53.
12. Sergeeva OA. GABAergic transmission in hepatic encephalopathy. Arch Biochem Biophys 2013;536:122-130.
13. Jones EA. Ammonia, the GABA neurotransmitter system, and hepatic encephalopathy. Metab Brain Dis 2002;17:275-281.
14. Kerlan RK Jr, LaBerge JM, Baker EL, et al. Successful reversal of hepatic encephalopathy with intentional occlusion of transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol 1995;6:917-921.
15. McCrea M, Cordoba J, Vessey G, Blei AT, Randolph C. Neuropsychological characterization and detection of subclinical hepatic encephalopathy. Arch Neurol 1996;53:758-763.
16. Weissenborn K, Bokemeyer M, Krause J, Ennen J, Ahl B. Neurological and neuropsychiatric syndromes associated with liver disease. AIDS 2005;19 Suppl 3:S93-S98.
17. Montagnese S, De Pittà C, De Rui M, et al. Sleep-wake abnormalities in patients with cirrhosis. Hepatology 2014;59:705-712.
18. Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology 2009;50:2014-2021.
19. Bajaj JS, Schubert CM, Heuman DM, et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology 2010;138:2332-2340.
20. Umapathy S, Dhiman RK, Grover S, Duseja A, Chawla YK. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Am J Gastroenterol 2014;109:1011-1019.
21. Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther 2010;31:537-547.
22. 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.
23. Bajaj JS, Heuman DM, Sterling RK, et al. Validation of encephalapp, smartphone-based stroop test, for the diagnosis of covert hepatic encephalopathy. Clin Gastroenterol Hepatol 2015;13:1828-1835.e1.
24. Sharma P, Sharma BC, Sarin SK. Critical flicker frequency for diagnosis and assessment of recovery from minimal hepatic encephalopathy in patients with cirrhosis. Hepatobiliary Pancreat Dis Int 2010;9:27-32.
25. Montagnese S, Amodio P, Morgan MY. Methods for diagnosing hepatic encephalopathy in patients with cirrhosis: a multidimensional approach. Metab Brain Dis 2004;19:281-312.
26. Bajaj JS, Cordoba J, Mullen KD, et al. 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.
27. Conn HO, Leevy CM, Vlahcevic ZR, et al. 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.
28. Ge PS, Runyon BA. Serum ammonia level for the evaluation of hepatic encephalopathy. JAMA 2014;312:643-644.
29. Bustamante J, Rimola A, Ventura PJ, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol 1999;30:890-895.
30. Christensen E, Krintel JJ, Hansen SM, Johansen JK, Juhl E. Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis: survival and prognostic factors. Scand J Gastroenterol 1989;24:999-1006.
31. Saunders JB, Walters JR, Davies AP, Paton A. A 20-year prospective study of cirrhosis. Br Med J (Clin Res Ed) 1981;282:263-266.
32. Fichet J, Mercier E, Genée O, et al. Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy. J Crit Care 2009;24:364-370.
33. Wong RJ, Gish RG, Ahmed A. Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver Transpl 2014;20:1454-1461.
34. Patidar KR, Thacker LR, Wade JB, et al. Covert hepatic encephalopathy is independently associated with poor survival and increased risk of hospitalization. Am J Gastroenterol 2014;109:1757-1763.
35. Neff GW, Kemmer N, Duncan C, Alsina A. Update on the management of cirrhosis: focus on cost-effective preventative strategies. Clinicoecon Outcomes Res 2013;5:143-152.
36. Saab S. Evaluation of the impact of rehospitalization in the management of hepatic encephalopathy. Int J Gen Med 2015;8:165-173.
37. Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol 2012;107:247-252.
38. Riggio O, Ridola L, Pasquale C, et al. Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol 2011;9:181-183.
39. Bajaj JS, Saeian K, Schubert CM, et al. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 2009;50:1175-1183.
40. Kircheis G, Knoche A, Hilger N, et al. Hepatic encephalopathy and fitness to drive. Gastroenterology 2009;137:1706-1715.e9.
41. Román E, Córdoba J, Torrens M, et al. Minimal hepatic encephalopathy is associated with falls. Am J Gastroenterol 2011;106:476-482.
42. Bajaj JS, Wade JB, Gibson DP, et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol 2011;106:1646-1653.
43. Strauss E, Tramote R, Silva EP, et al. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 1992;39:542-545.
44. Amodio P, Bemeur C, Butterworth R, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology 2013;58:325-336.
45. Chadalavada R, Sappati Biyyani RS, Maxwell J, Mullen K. Nutrition in hepatic encephalopathy. Nutr Clin Pract 2010;25:257-264.
46. Bémeur C, Desjardins P, Butterworth RF. Role of nutrition in the management of hepatic encephalopathy in end-stage liver failure. J Nutr Metab 2010;2010:489823.
47. Holecek M. Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications. Nutrition 2013;29:1186-1191.
48. Holecek M. Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy. Nutrition 2015;31:14-20.
49. Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol 2012;27:430-441.
50. Gluud LL, Dam G, Borre M, et al. Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. J Nutr 2013;143:1263-1268.
51. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014;60:715-735.
52. Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev 2004;2:CD003044.
53. Sharma P, Sharma BC, Sarin SK. Predictors of nonresponse to lactulose in patients with cirrhosis and hepatic encephalopathy. Eur J Gastroenterol Hepatol 2010;22:526-531.
54. Bajaj JS, Sanyal AJ, Bell D, Gilles H, Heuman DM. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharmacol Ther 2010;31:1012-1017.
55. Sharma P, Sharma BC, Agrawal A, Sarin SK. Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose. J Gastroenterol Hepatol 2012;27:1329-1335.
56. Bajaj JS, Pinkerton SD, Sanyal AJ, Heuman DM. Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis. Hepatology 2012;55:1164-1171.
57. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010;362:1071-1081.
58. Mullen KD, Sanyal AJ, Bass NM, et al. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol 2014;12:1390-1397.e2.
59. Neff GW, Jones M, Broda T, et al. Durability of rifaximin response in hepatic encephalopathy. J Clin Gastroenterol 2012;46:168-171.
60. Mohammad RA, Regal RE, Alaniz C. Combination therapy for the treatment and prevention of hepatic encephalopathy. Ann Pharmacother 2012;46:1559-1563.
61. Leise MD, Poterucha JJ, Kamath PS, Kim WR. Management of hepatic encephalopathy in the hospital. Mayo Clin Proc 2014;89:241-253.
62. 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.
63. Jiang Q, Jiang XH, Zheng MH, Jiang LM, Chen YP, Wang L. Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta-analysis. Eur J Gastroenterol Hepatol 2008;20:1064-1070.
64. Sharma BC, Sharma P, Lunia MK, Srivastava S, Goyal R, Sarin SK. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol 2013;108:1458-1463.
65. Hawkins RA, Jessy J, Mans AM, Chedid A, DeJoseph MR. Neomycin reduces the intestinal production of ammonia from glutamine. Adv Exp Med Biol 1994;368:125-134.
66. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut 1982;23:1-7.
67. Shavakhi A, Hashemi H, Tabesh E, et al. Multistrain probiotic and lactulose in the treatment of minimal hepatic encephalopathy. J Res Med Sci 2014;19:703-708.
68. Dhiman RK, Rana B, Agrawal S, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 2014;147:1327-1337.e3.
69. Lunia MK, Sharma BC, Sharma P, Sachdeva S, Srivastava S. Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial. Clin Gastroenterol Hepatol 2014;12:1003-1008.e1.
70. Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label, randomized controlled trial of lactulose, probiotics, and no therapy. Am J Gastroenterol 2012;107:1043-1050.
71. Zhao LN, Yu T, Lan SY, et al. Probiotics can improve the clinical outcomes of hepatic encephalopathy: an update meta-analysis. Clin Res Hepatol Gastroenterol 2015;39:674-682.
72. Manning RT, Delp M. Management of hepatocerebral intoxication. N Engl J Med 1958;258:55-62.
73. Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350: electrolyte solution for treatment of overt hepatic encephalopathy. The HELP randomized clinical trial. JAMA Intern Med 2014;174:1727-1733.
74. Laccetti M, Manes G, Uomo G, Lioniello M, Rabitti PG, Balzano A. Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study. Dig Liver Dis 2000;32:335-338.
75. Rockey DC, Vierling JM, Mantry P, et al. Randomized, doubleblind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology 2014;59:1073-1083.
76. Ventura-Cots M, Arranz JA, Simón-Talero M, et al. Safety of ornithine phenylacetate in cirrhotic decompensated patients: an open-label, dose-escalating, single-cohort study. J Clin Gastroenterol 2013;47:881-887.
77. Jover-Cobos M, Khetan V, Jalan R. Treatment of hyperammonemia in liver failure. Curr Opin Clin Nutr Metab Care 2014;17:105-110.
78. Bai M, Yang Z, Qi X, Fan D, Han G. l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a metaanalysis of randomized controlled trials. J Gastroenterol Hepatol 2013;28:783-792.
79. Sundaram V, Shaikh OS. Hepatic encephalopathy: pathophysiology and emerging therapies. Med Clin North Am 2009;93:819-836.
80. Chavez-Tapia NC, Cesar-Arce A, Barrientos-Gutiérrez T, Villegas-López FA, Méndez-Sanchez N, Uribe M. A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy. Nutr J 2013;12:74.
81. Mukund A, Rajesh S, Arora A, Patidar Y, Jain D, Sarin SK. Efficacy of balloon-occluded retrograde transvenous obliteration of large spontaneous lienorenal shunt in patients with severe recurrent hepatic encephalopathy with foam sclerotherapy: initial experience. J Vasc Interv Radiol 2012;23:1200-1206.
82. An J, Kim KW, Han S, Lee J, Lim YS. Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy. Aliment Pharmacol Ther 2014;39:1418-1426.
83. Laleman W, Simon-Talero M, Maleux G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology 2013;57:2448-2457.
84. Zuckerman DA, Darcy MD, Bocchini TP, Hildebolt CF. Encephalopathy after transjugular intrahepatic portosystemic shunting: analysis of incidence and potential risk factors. AJR Am J Roentgenol 1997;169:1727-1731.
85. Forauer AR, McLean GK. Transjugular intrahepatic portosystemic shunt constraining stent for the treatment of refractory postprocedural encephalopathy: a simple design utilizing a Palmaz stent and Wallstent. J Vasc Interv Radiol 1998;9:443-446.
86. Sanyal AJ, Freedman AM, Shiffman ML, Purdum PP 3rd, Luketic VA, Cheatham AK. Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study. Hepatology 1994;20(1 Pt 1):46-55.
87. Riggio O, Merlli M, Pedretti G, et al. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: incidence and risk factors. Dig Dis Sci 1996;41:578-584.
88. Bureau C, Garcia-Pagan JC, Otal P, et al. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology 2004;126:469-475.
89. Yang Z, Han G, Wu Q, et al. Patency and clinical outcomes of transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stents versus bare stents: a meta-analysis. J Gastroenterol Hepatol 2010;25:1718-1725.
90. Riggio O, Nardelli S, Moscucci F, Pasquale C, Ridola L, Merli M. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Clin Liver Dis 2012;16:133-146.
91. Riggio O, Ridola L, Lucidi C, Angeloni S. Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines? Dig Liver Dis 2010;42:462-467.
92. Bai M, Qi X, Yang Z, et al. Predictors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in cirrhotic patients: a systematic review. J Gastroenterol Hepatol 2011;26:943-951.
93. Guevara M, Baccaro ME, Ríos J, et al. Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. Liver Int 2010;30:1137-1142.
94. Riggio O, Masini A, Efrati C, et al. Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol 2005;42:674-679.
95. Fanelli F, Salvatori FM, Rabuffi P, et al. Management of refractory hepatic encephalopathy after insertion of TIPS: longterm results of shunt reduction with hourglass-shaped balloonexpandable stent-graft. AJR Am J Roentgenol 2009;193:1696-1702.
96. Catalina MV, Barrio J, Anaya F, et al. Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure. Liver Int 2003;23 Suppl 3:39-43.
97. Sen S, Mookerjee RP, Cheshire LM, Davies NA, Williams R, Jalan R. Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol 2005;43:142-148.
98. Laleman W, Wilmer A, Evenepoel P, et al. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care 2006;10:R108
99. Bañares R, Nevens F, Larsen FS, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 2013;57:1153-1162.
100. Amodio P. Hepatic encephalopathy. In: Lee SS, Moreau R, eds. Cirrhosis: a practical guide to management. Chichester: John Wiley & Sons, 2015:105-123.