Evolving concepts: The negative effect of minimal hepatic encephalopathy and role for prophylaxis in patients with cirrhosis

Clinical Therapeutics

Volumn 35, Issue 9, 2013, Pages 1458-1473

  Prakash, Ravi K ^a   Kanna, Sowjanya ^a   Mullen, Kevin D ^a  

^a METROHEALTH MEDICAL CENTER   (United States)

Author keywords

Cirrhosis; Hepatic encephalopathy; Lactulose; Minimal; Overt; Probiotics; Rifaximin

Indexed keywords

AMMONIA; BENZODIAZEPINE; LACTITOL; LACTULOSE; METRONIDAZOLE; NEOMYCIN; PAROMOMYCIN; PLACEBO; PROBIOTIC AGENT; RIFAXIMIN; VANCOMYCIN;

ABDOMINAL CRAMP; ABDOMINAL PAIN; ALGORITHM; ANTIBIOTIC RESISTANCE; ATTENTION; BLOATING; BLOOD BRAIN BARRIER; CAREGIVER; CLINICAL PRACTICE; COGNITION; CONSENSUS; DEPTH PERCEPTION; DIARRHEA; ENERGY METABOLISM; FLATULENCE; GASTROINTESTINAL SYMPTOM; HEALTH CARE QUALITY; HEPATIC ENCEPHALOPATHY; HUMAN; LIVER CIRRHOSIS; LIVER TRANSPLANTATION; META ANALYSIS; MICROBIAL ACTIVITY; MOTOR PERFORMANCE; NEPHROTOXICITY; NEUROTRANSMISSION; OTOTOXICITY; OXIDATIVE STRESS; PERIPHERAL NEUROPATHY; PORTOSYSTEMIC ANASTOMOSIS; PRACTICE GUIDELINE; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SOCIAL STATUS; SYSTEMATIC REVIEW;

CIRRHOSIS; HEPATIC ENCEPHALOPATHY; LACTULOSE; MINIMAL; OVERT; PROBIOTICS; RIFAXIMIN;

ANTI-INFECTIVE AGENTS; CLINICAL TRIALS AS TOPIC; GASTROINTESTINAL AGENTS; GASTROINTESTINAL TRACT; HEPATIC ENCEPHALOPATHY; HUMANS; LACTULOSE; LIVER CIRRHOSIS; PROBIOTICS; QUALITY OF LIFE; RIFAMYCINS;

EID: 84884356032     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2013.07.421     Document Type: Review

References (96)

1. Bustamante J., Rimola A., Ventura P.J., et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol 1999, 30:890-895.
2. Stewart C.A., Smith G.E. Minimal hepatic encephalopathy. Nat Clin Pract Gastroenterol Hepatol 2007, 4:677-685.
3. Bismuth M., Funakoshi N., Cadranel J.F., Blanc P. Hepatic encephalopathy: from pathophysiology to therapeutic management. Eur J Gastroenterol Hepatol 2011, 23:8-22.
4. Khungar V., Poordad F. Hepatic encephalopathy. Clin Liver Dis 2012, 16:301-320.
5. Patel D., McPhail M.J., Cobbold J.F., Taylor-Robinson S.D. Hepatic encephalopathy. Br J Hosp Med (Lond) 2012, 73:79-85.
6. Haussinger D., Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut 2008, 57:1156-1165.
7. Mullen K.D., Ferenci P., Bass N.M., et al. An algorithm for the management of hepatic encephalopathy. Semin Liver Dis 2007, 27(Suppl 2):32-48.
8. Riordan S.M., Williams R. Gut flora and hepatic encephalopathy in patients with cirrhosis. N Engl J Med 2010, 362:1140-1142.
9. Shawcross D., Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 2005, 62:2295-2304.
10. Riordan S.M., Williams R. Treatment of hepatic encephalopathy. N Engl J Med 1997, 337:473-479.
11. Williams R. Review article: bacterial flora and pathogenesis in hepatic encephalopathy. Aliment Pharmacol Ther 2007, 25(Suppl 1):17-22.
12. Sundaram V., Shaikh O.S. Hepatic encephalopathy: pathophysiology and emerging therapies. Med Clin North Am 2009, 93:819-836. vii.
13. Frederick R.T. Current concepts in the pathophysiology and management of hepatic encephalopathy. Gastroenterol Hepatol (N Y) 2011, 7:222-233.
14. Zamora Nava L.E., Torre D.A. Minimal hepatic encephalopathy. Ann Hepatol 2011, 10(Suppl 2):S50-S54.
15. Montgomery J.Y., Bajaj J.S. Advances in the evaluation and management of minimal hepatic encephalopathy. Curr Gastroenterol Rep 2011, 13:26-33.
16. Prasad S., Dhiman R.K., Duseja A., et al. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 2007, 45:549-559.
17. Butterworth R.F. Editorial: rifaximin and minimal hepatic encephalopathy. Am J Gastroenterol 2011, 106:317-318.
18. Groeneweg M., Quero J.C., De Bruijn I., et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 1998, 28:45-49.
19. Schomerus H., Hamster W. Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain Dis 2001, 16:37-41.
20. Arguedas M.R., DeLawrence T.G., McGuire B.M. Influence of hepatic encephalopathy on health-related quality of life in patients with cirrhosis. Dig Dis Sci 2003, 48:1622-1626.
21. Wein C., Koch H., Popp B., et al. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology 2004, 39:739-745.
22. Bajaj J.S., Hafeezullah M., Hoffmann R.G., Saeian K. Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations. Am J Gastroenterol 2007, 102:1903-1909.
23. Bajaj J.S., Saeian K., Hafeezullah M., et al. Patients with minimal hepatic encephalopathy have poor insight into their driving skills. Clin Gastroenterol Hepatol 2008, 6:1135-1139.
24. Bajaj J.S., Hafeezullah M., Hoffmann R.G., et al. Navigation skill impairment: another dimension of the driving difficulties in minimal hepatic encephalopathy. Hepatology 2008, 47:596-604.
25. Kim Y., Park G., Lee M., Lee J.H. Impairment of driving ability and neuropsychological function in patients with MHE disease. Cyberpsychol Behav 2009, 12:433-436.
26. Bajaj J.S., Saeian K., Schubert C.M., et al. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology 2009, 50:1175-1183.
27. Bajaj J.S., Hafeezullah M., Zadvornova Y., et al. The effect of fatigue on driving skills in patients with hepatic encephalopathy. Am J Gastroenterol 2009, 104:898-905.
28. Roman E., Cordoba J., Torrens M., et al. Minimal hepatic encephalopathy is associated with falls. Am J Gastroenterol 2011, 106:476-482.
29. Bianchi G., Giovagnoli M., Sasdelli A.S., Marchesini G. Hepatic encephalopathy and health-related quality of life. Clin Liver Dis 2012, 16:159-170.
30. Prakash R.K., Brown T.A., Mullen K.D. Minimal hepatic encephalopathy and driving: is the genie out of the bottle?. Am J Gastroenterol 2011, 106:1415-1416.
31. Hartmann I.J., Groeneweg M., Quero J.C., et al. The prognostic significance of subclinical hepatic encephalopathy. Am J Gastroenterol 2000, 95:2029-2034.
32. Stewart C.A., Malinchoc M., Kim W.R., Kamath P.S. Hepatic encephalopathy as a predictor of survival in patients with end-stage liver disease. Liver Transpl 2007, 13:1366-1371.
33. Bajaj J.S., Wade J.B., Gibson D.P., et al. The multi-dimensional burden of cirrhosis and hepatic encephalopathy on patients and caregivers. Am J Gastroenterol 2011, 106:1646-1653.
34. Kappus M.R., Bajaj J.S. Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests). Clin Liver Dis 2012, 16:43-55.
35. Weissenborn K. Psychometric tests for diagnosing minimal hepatic encephalopathy. Metab Brain Dis 2013, 28:227-229.
36. Prakash R., Mullen K.D. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010, 7:515-525.
37. Ferenci P, Lockwood A, Mullen K, et al. 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.
38. Weissenborn K., Ennen J.C., Schomerus H., et al. Neuropsychological characterization of hepatic encephalopathy. J Hepatol 2001, 34:768-773.
39. Randolph C., Hilsabeck R., Kato A., et al. Neuropsychological assessment of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 2009, 29:629-635.
40. Bajaj J.S., Hafeezullah M., Franco J., et al. Inhibitory control test for the diagnosis of minimal hepatic encephalopathy. Gastroenterology 2008, 135:1591-1600.
41. Mardini H., Saxby B.K., Record C.O. Computerized psychometric testing in minimal encephalopathy and modulation by nitrogen challenge and liver transplant. Gastroenterology 2008, 135:1582-1590.
42. Overview and features of the ImPACT test. 2012. Accessed April 16, 2013. http://impacttest.com/about/background.
43. Tsushima M., Tsushima W., Tsushima V., et al. A case control study of impact: a brief and effective web-based neuropsychological assessment battery to diagnose minimal hepatic encephalopathy (MHE). J Hepatol 2010, 52(Suppl):S87. (Abstract).
44. Romero-Gomez M., Cordoba J., Jover R., et al. Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology 2007, 45:879-885.
45. Kircheis G., Wettstein M., Timmermann L., et al. Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology 2002, 35:357-366.
46. Sharma P., Sharma B.C., Sarin S.K. 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.
47. Kircheis G., Fleig W.E., Gortelmeyer R., et al. Assessment of low-grade hepatic encephalopathy: a critical analysis. J Hepatol 2007, 47:642-650.
48. Allampati S., Prakash R., Perzynski A., et al. Does inhibitory control test (ICT) diagnose minimal hepatic encephalopathy (MHE)?. Am J Gastroenterol Suppl 2012, 107(Suppl 1):S190-S191. (Abstract).
49. Karanth P., Chikkanna R., Allampati S., et al. Effect of computer literacy on psychometric test performance in the diagnosis of minimal hepatic encephalopathy. Am J Gastroenterol 2013, 107(Suppl 1):S194. (Abstract).
50. Bajaj J.S., Etemadian A., Hafeezullah M., Saeian K. Testing for minimal hepatic encephalopathy in the United States: an AASLD survey. Hepatology 2007, 45:833-834.
51. Malaguarnera M., Greco F., Barone G., et al. Bifidobacterium longum with fructo-oligosaccharide (FOS) treatment in minimal hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Dig Dis Sci 2007, 52:3259-3265.
52. Sharma P., Sharma B.C., Puri V., Sarin S.K. An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol 2008, 20:506-511.
53. Liu Q., Duan Z.P., Ha D.K., et al. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 2004, 39:1441-1449.
54. Lata J., Jurankova J., Pribramska V., et al. Effect of administration of Escherichia coli Nissle (Mutaflor) on intestinal colonisation, endo-toxemia, liver function and minimal hepatic encephalopathy in patients with liver cirrhosis. Vnitr Lek 2006, 52:215-219.
55. Bajaj J.S., Saeian K., Christensen K.M., et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy. Am J Gastroenterol 2008, 103:1707-1715.
56. Saji S., Kumar S., Thomas V. A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy. Trop Gastroenterol 2011, 32:128-132.
57. Loria A., Escheik C., Gerber N.L., Younossi Z.M. Quality of life in cirrhosis. Curr Gastroenterol Rep 2013, 15:301.
58. Afendy A., Kallman J.B., Stepanova M., et al. Predictors of health-related quality of life in patients with chronic liver disease. Aliment Pharmacol Ther 2009, 30:469-476.
59. Sidhu S.S., Goyal O., Mishra B.P., et al. 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.
60. Bajaj J.S., Heuman D.M., Wade J.B., et al. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology 2011, 140:478-487.
61. Shukla S., Shukla A., Mehboob S., Guha S. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther 2011, 33:662-671.
62. Blei A.T., Cordoba J. Hepatic encephalopathy. Am J Gastroenterol. 2001, 96:1968-1976.
63. Luo M., Li L., Lu C.Z., Cao W.K. Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy: a meta-analysis. Eur J Gastroenterol Hepatol 2011, 23:1250-1257.
64. Agrawal A., Sharma B.C., Sharma P., Sarin S.K. 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.
65. Watanabe A., Sakai T., Sato S., et al. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997, 26:1410-1414.
66. Morgan M.Y., Alonso M., Stanger L.C. Lactitol and lactulose for the treatment of subclinical hepatic encephalopathy in cirrhotic patients. A randomised, cross-over study. J Hepatol 1989, 8:208-217.
67. Dhiman R.K., Sawhney M.S., Chawla Y.K., et al. Efficacy of lactulose in cirrhotic patients with subclinical hepatic encephalopathy. Dig Dis Sci 2000, 45:1549-1552.
68. Horsmans Y., Solbreux P.M., Daenens C., et al. Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy. Aliment Pharmacol Ther 1997, 11:165-170.
69. Zeng Z., Li Y.Y. Effects of lactulose treatment on the course of subclinical hepatic encephalopathy. Zhonghua Yi Xue Za Zhi 2003, 83:1126-1129.
70. Sharma P., Sharma B., Agrawal A., Sarin S. Primary prophylaxis of hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose. Am J Gastroenterol 2010, 105(Suppl 1):S104-S105. (Abstract).
71. Bajaj J.S., Sanyal A.J., Bell D., et al. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharmacol Ther 2010, 31:1012-1017.
72. Leevy C.B., Phillips J.A. Hospitalizations during the use of rifaximin versus lactulose for the treatment of hepatic encephalopathy. Dig Dis Sci 2007, 52:737-741.
73. Pantham G., Waghray N., Prakash R., et al. Overt hepatic encephalopathy in cirrhosis: influence of multiple clinical precipitants resulting in hospitalization. Gastroenterology 2012, 142(Suppl 1):S950. (Abstract).
74. Kalaitzakis E., Simren M., Olsson R., et al. Gastrointestinal symptoms in patients with liver cirrhosis: associations with nutritional status and health-related quality of life. Scand J Gastroenterol 2006, 41:1464-1472.
75. Seyan A.S., Hughes R.D., Shawcross D.L. Changing face of hepatic encephalopathy: role of inflammation and oxidative stress. World J Gastroenterol 2010, 16:3347-3357.
76. Maccaferri S., Vitali B., Klinder A., et al. Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. J Antimicrob Chemother 2010, 65:2556-2565.
77. Bajaj J.S., Heuman D.M., Sanyal A.J., et al. Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy. PLoS One 2013, 8:e60042.
78. Xifaxan (rifaximin) tablets [package insert]. Raleigh, NC: Salix Pharmaceuticals, Inc; 2012.
79. Mullen K., Prakash R. Rifaximin for the treatment of hepatic encephalopathy. Expert Rev Gastroenterol Hepatol 2010, 4:665-677.
80. Brigidi P., Swennen E., Rizzello F., et al. Effects of rifaximin administration on the intestinal microbiota in patients with ulcerative colitis. J Chemother 2002, 14:290-295.
81. DuPont H.L., Jiang Z.D., Okhuysen P.C., et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers' diarrhea. Ann Intern Med 2005, 142:805-812.
82. Bass N.M., Mullen K.D., Sanyal A., et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med 2010, 362:1071-1081.
83. Testa R., Eftimiadi C., Sukkar G.S., et al. A non-absorbable rifamycin for treatment of hepatic encephalopathy. Drugs Exp Clin Res 1985, 11:387-392.
84. Grande L., Jover M., Fobelo M., et al. Double-blinded crossover trial analyzing the usefulness of rifaxamin in the treatment of minimal hepatic encephalopathy (MHE): an interim analysis. J Hepatol 2010, 52(Suppl):S206-S207. (Abstract).
85. Healthcare Cost & Utilization Project (HCUP). 2012. Accessed March 22, 2012. http://www.ahrq.gov/data/hcup/.
86. Fichet J., Mercier E., Genee O., et al. Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy. J Crit Care 2009, 24:364-370.
87. Bajaj J.S., Schubert C.M., Heuman D.M., et al. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology 2010, 138:2332-2340.
88. Campagna F., Biancardi A., Montagnese S., et al. Incomplete reversal of cognitive dysfunction after liver transplantation in individuals who had had overt hepatic encephalopathy before liver transplantation. J Hepatol 2010, 52(Suppl):S187. (Abstract).
89. Garcia-Martinez R., Rovira A., Alonso J., et al. Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume. Liver Transpl 2011, 17:38-46.
90. 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.
91. Quero Guillen J.C., Groeneweg M., Jimenez S.M., et al. Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?. Rev Esp Enferm Dig 2002, 94:544-557.
92. Bajaj J.S. Management options for minimal hepatic encephalopathy. Expert Rev Gastroenterol Hepatol 2008, 2:785-790.
93. Ortiz M., Jacas C., Cordoba J. Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 2005, 42(Suppl 1):S45-S53.
94. Bajaj J.S., Pinkerton S.D., Sanyal A.J., Heuman D.M. Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis. Hepatology 2012, 55:1164-1171.
95. Amodio P., Montagnese S., Merkel C. Attention: minimal hepatic encephalopathy and road accidents. Hepatology 2012, 55:985-987.
96. Bajaj J.S., Cordoba J., Mullen K.D., 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.