title: Current trends in the treatment of hepatic encephalopathy.
abstract: Hepatic encephalopathy (HE) is a common reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction and significant morbidity and mortality. Although a clear pathogenesis is yet to be determined, elevated ammonia in the serum and central nervous system are the mainstay for pathogenesis and treatment. Management includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, hepatocellular carcinoma, dehydration, hypotension, and use of benzodiazepines, psychoactive drugs, and/or alcohol). Clinical trials have established the efficacy of lactulose and lactitol enemas in the treatment of acute hepatic encephalopathy. Extensive clinical experience has demonstrated the efficacy of oral lactulose and lactitol with the goal of two to three soft bowel movements a day for the treatment of chronic HE. However, lactulose and lactitol have significant gastrointestinal side effects. For patients unable to tolerate lactulose or lactitol or who still have persistent chronic HE with lactulose or lactitol, neomycin, metronidazole and rifaximin are second-line agents. More recent data supports the benefits of rifaximin used solely and as an additional agent with fewer side effects than neomycin or metronidazole. Newer therapies being investigated in humans with clinical promise include nitazoxanide, the molecular adsorbent recirculating system (MARS), L-ornithine phenylacetate, sodium benzoate, and/or sodium phenylacetate and Kremezin((R)) (AST-120).
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Mohamad Rasm
authors.initials: MR
authors.lastname: Al Sibae
authors.forename: Brendan M
authors.initials: BM
authors.lastname: McGuire
references.citation: J Hepatol. 1995 Jul;23(1):39-46
references.pmid: 8530808
references.citation: J Neural Transm Suppl. 1978;(14):87-94
references.pmid: 290744
references.citation: Gastroenterology. 1977 Apr;72(4 Pt 1):573-83
references.pmid: 14049
references.citation: Hepatology. 1987 Jul-Aug;7(4):639-43
references.pmid: 3301614
references.citation: Gastroenterology. 1989 Oct;97(4):1033-42
references.pmid: 2506095
references.citation: Hepatology. 2005 Nov;42(5):1158-65
references.pmid: 16250033
references.citation: Hepatology. 2002 Mar;35(3):716-21
references.pmid: 11870389
references.citation: Lancet. 1991 May 25;337(8752):1250-3
references.pmid: 1674063
references.citation: Ann Intern Med. 1963 Jan;58:1-24
references.pmid: 13978712
references.citation: AJNR Am J Neuroradiol. 1998 Oct;19(9):1681-6
references.pmid: 9802491
references.citation: Gut. 1982 Jan;23(1):1-7
references.pmid: 7035298
references.citation: Ther Apher Dial. 2007 Jun;11(3):189-95
references.pmid: 17498000
references.citation: Am J Gastroenterol. 2001 Jul;96(7):1968-76
references.pmid: 11467622
references.citation: Hepatology. 1997 Mar;25(3):551-6
references.pmid: 9049197
references.citation: Hepatology. 2007 Apr;45(4):879-85
references.pmid: 17393525
references.citation: Am J Gastroenterol. 1986 Jul;81(7):540-3
references.pmid: 3717115
references.citation: Hepatology. 1990 Jun;11(6):1083-4
references.pmid: 2142117
references.citation: Gut. 1978 Nov;19(11):1068-73
references.pmid: 730076
references.citation: Med Hypotheses. 2007;69(5):1064-9
references.pmid: 17467190
references.citation: Gastroenterology. 1979 Jun;76(6):1347-51
references.pmid: 374177
references.citation: Hepatogastroenterology. 1992 Dec;39(6):542-5
references.pmid: 1483668
references.citation: J Hepatol. 1999 May;30(5):890-5
references.pmid: 10365817
references.citation: Hepatology. 1992 Jul;16(1):138-44
references.pmid: 1618465
references.citation: Hepatology. 1994 Jul;20(1 Pt 1):46-55
references.pmid: 8020904
references.citation: J Hepatol. 1998 May;28(5):856-64
references.pmid: 9625322
references.citation: Cochrane Database Syst Rev. 2001;(4):CD002798
references.pmid: 11687160
references.citation: Eur J Med. 1993 Aug-Sep;2(7):414-6
references.pmid: 8258031
references.citation: Hepatology. 1996 May;23(5):1084-92
references.pmid: 8621138
references.citation: Hepatology. 1997 Jun;25(6):1351-60
references.pmid: 9185752
references.citation: Cochrane Database Syst Rev. 2004;(2):CD003044
references.pmid: 15106187
references.citation: Hepatology. 2007 Mar;45(3):549-59
references.pmid: 17326150
references.citation: Hepatology. 2004 May;39(5):1441-9
references.pmid: 15122774
references.citation: J Intern Med. 1993 May;233(5):385-92
references.pmid: 8068051
references.citation: Am J Physiol. 1991 Aug;261(2 Pt 1):C310-8
references.pmid: 1872373
references.citation: Metab Brain Dis. 2004 Dec;19(3-4):331-43
references.pmid: 15554425
references.citation: Hepatology. 1987 Nov-Dec;7(6):1278-84
references.pmid: 3315932
references.citation: J Hepatol. 2007 Jul;47(1):67-73
references.pmid: 17459511
references.citation: Hepatogastroenterology. 2005 Jan-Feb;52(61):203-7
references.pmid: 15783031
references.citation: Hepatology. 2002 Feb;35(2):357-66
references.pmid: 11826409
references.citation: Can J Surg. 1979 May;22(3):274-7
references.pmid: 436029
references.citation: J Hepatol. 2001 May;34(5):768-73
references.pmid: 11434627
references.citation: Hepatology. 1997 Apr;25(4):820-7
references.pmid: 9096582
references.citation: Clin Gastroenterol Hepatol. 2005 Feb;3(2):184-91
references.pmid: 15704053
references.citation: Hepatology. 2007 Dec;46(6):1853-62
references.pmid: 17975845
references.citation: Hepatology. 2004 Jul;40(1):73-9
references.pmid: 15239088
references.citation: Hepatology. 1991 Apr;13(4):812-3
references.pmid: 1826283
references.citation: J Pediatr. 2001 Jan;138(1 Suppl):S46-54; discussion S54-5
references.pmid: 11148549
references.citation: J Hepatol. 2003 Jan;38(1):51-8
references.pmid: 12480560
references.citation: Pharmacotherapy. 2008 Aug;28(8):1019-32
references.pmid: 18657018
references.citation: N Engl J Med. 1997 Aug 14;337(7):473-9
references.pmid: 9250851
references.citation: Semin Liver Dis. 1996 Aug;16(3):235-44
references.pmid: 8989809
references.citation: J Hepatol. 2004 Jul;41(1):38-43
references.pmid: 15246205