Rifaximin reduces EEG relative beta power in patients with minimal hepatic encephalopathy: preliminary findings
Plasma benzodiazepine-like compounds (Bzd-L-Cs) are detectable in normal subjects, and their concentration increases in patients with progressive chronic liver disease. Bzd-L-Cs may precipitate hepatic encephalopathy (HE). The intestinal bacterial flora has been implicated in the production of Bzd-L-Cs and treatment with rifaximin may reduce their levels in patients with cirrhosis. Bzd-L-Cs increase EEG beta activity. We determined whether rifaximin treatment reduces EEG beta activity in patients with cirrhosis and minimal HE (mHE).
Eleven one-week courses of treatment, 8 rifaximin 600 to 1200 mg/day and 3 placebo, were randomly and blindly assigned to 5 cirrhotic patients with mHE (abnormal number connection test, symbol digit test or EEG).
After treatment, the relative beta power of the EEG decreased in the rifaximin-treated group (Wilcoxon paired test: Z = 2.1, p = 0.03), but not in the placebo-treated group (Z = 1.07, p NS). The EEG mean dominant frequency did not change. Psychometric tests did not change significantly; there was a trend for NCT to improve in the rifaximin-treated group (Wilcoxon paired test: Z = 1.7, p = 0.08).
In conclusion, the reduction of EEG beta activity in rifaximin-treated patients with mHE is compatible with previous observations that demonstrated a decrease in Bzd-L-C blood levels in patients with cirrhosis, who underwent rifaximin treatment.
KeywordsPlacebo Hepatitis Urea Creatinine Manes
Availone R, Zeneroli ML, Venturini I, Corsi L, Schreier P, Kleinschnitz M et al.
Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy. Gut 1998; 42: 861–867.CrossRefGoogle Scholar
Baraldi M, Availone R, Corsi L, Venturini I, Baraldi C and Zeneroli ML. Endogenous benzodiazepines. Therapie 2000; 55: 143–146.PubMedGoogle Scholar
Barbaro G, Di Lorenzo G, Soldini M, Marziali M, Bellomo G, Belloni G et al.
Flumazenil for hepatic coma in patients with liver cirrhosis: an Italian multicentre double-blind, placebo-controlled, crossover study. Eur J Emerg Med 1998; 5: 213–218.PubMedCrossRefGoogle Scholar
Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, Bellomo G, Belloni G et al.
Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo-controlled, cross-over study. Hepatology 1998; 28: 374–378.PubMedCrossRefGoogle Scholar
Gyr K, Meier R, Haussler J, Bouletreau P, Fleig WE, Gatta A et al.
Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study. Gut 1996; 39: 319–324.PubMedCrossRefGoogle Scholar
Pomier-Layrargues G, Giguere JF, Lavoie J, Perney P, Gagnon S, D’Amour M et al.
Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial. Hepatology 1994; 19: 32–37.PubMedGoogle Scholar
Laccetti M, Manes G, Uomo G, Lioniello M, Rabitti PG and 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.PubMedCrossRefGoogle Scholar
Zeneroli ML, Venturini I, Stefaneiii S, Farina F, Miglioli RC, Minelli E et al.
Antibacterial activity of rifaximin reduces the levels of benzodiazepine-like compounds in patients with liver cirrhosis. Pharmacol Res 1997; 35: 557–560.PubMedCrossRefGoogle Scholar
Joy RM, Hance AJ, and Killam KF, Jr. A quantitative electroencephalographic comparison of some benzodiazepines in the primate. Neuropharmacology 1971; 10: 483–497.PubMedCrossRefGoogle Scholar
Klem GH, Luders HO, Jasper HH and Elger C. The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999; 52: 3–6.PubMedGoogle Scholar
Amodio P, Marchetti P, Del Piccolo F, de Tourtchaninoff M, Varghese P, Zuliani C et al.
Spectral versus visual EEG analysis in mild hepatic encephalopathy. Clin Neurophysiol 1999; 110: 1334–1344.PubMedCrossRefGoogle Scholar
Amodio P, Wenin H, Del Piccolo F, Mapelli D, Montagnese S, Pellegrini A et al.
Variability of Trailmaking Tests, Symbol Digit Test and Line Trait Test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clin Exp Res 2002; 14: 116–131.Google Scholar
Basile AS, Jones EA and Skolnick P. The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands. Pharmacol Rev 1991; 43: 27–71.PubMedGoogle Scholar
Jones EA and Basile AS. Does ammonia contribute to increased GABA-ergic neurotransmission in liver failure? Metab Brain Dis 1998; 13: 351–360.PubMedCrossRefGoogle Scholar
Mullen KD and Jones EA. Natural benzodiazepines and hepatic encephalopathy. Semin Liver Dis 1996; 16: 255–264.PubMedCrossRefGoogle Scholar
Bauer G. EEG, drugs effects, and central nervous system poisoning. In: Niedermeyer E, Lopes Da Silva F (Eds). Electroencephalography. Basic Principles, Clinical Applications, and Related Fields. Baltimore: Williams & Wilkins, 1993: 631–642.Google Scholar
Parsons-Smith BG, Summerskill WHJ, Dawson AM and Sherlock S. The electroencephalograph in liver disease. Lancet 1957; 2: 867–871.CrossRefGoogle Scholar
Gillis JC and Brogden RN. Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 1995; 49: 467–484.PubMedCrossRefGoogle Scholar
Puxeddu A, Quartini M, Massimetti A and Ferrieri A. Rifaximin in the treatment of chronic hepatic encephalopathy. Curr Med Res Opin 1995; 13: 274–281.PubMedCrossRefGoogle Scholar
Pedretti G, Calzetti C, Missale G and 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.PubMedGoogle Scholar
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