Abstract
Hepatic encephalopathy (HE) was characterized in humans 35 years ago and hyperammonemia was proposed from the start as the main factor involved in the pathogenesis of this complication. Thereafter, different therapies were tried in HE, all aimed at reducing blood ammonia. Surprisingly some of them were considered to be efficient in spite of the fact that controlled studies on their efficacy were lacking. Lactulose and neomycin are the best examples of these treatments. On the other hand, other treatments (such as arginine and ornithine) targetted at stimulation of the urea cycle were at first advocated, then neglected in spite of the fact that no scientific data were provided to deny their efficacy. The 1970’s and 1980’s saw the emergence of new pathogenetic theories such as the “false neurotransmitter” and the “GABA” hypotheses. At present, even the keenest supporters of these theories agree that ammonia remains a major determinant in the pathogenesis of HE. Therefore, it may be profitable to reassess the older treatments in the light of new methods developped to evaluate their efficacy. The first step is to determine the natural history of hepatic encephalopathy with multivariate analysis using hepatic function, the extent of portosystemic shunting and the nature of precipitating factors as variables. Such studies allow a stratification according to prognostic variables for future therapeutic trials. The second step is to improve the methods used to evaluate the grade of HE. Clinical assessment of HE is not standardized and is probably biased by poor inter-observer agreement. Measurement of blood ammonia should be performed under strictly defined conditions. New techniques such as evoked potentials should be adequately validated. Moreover, the design of future controlled randomized clinical trials should be markedly improved to allow valid conclusions. The studied population should be carefully defined; the sample size should be adequate since HE resolves itself spontaneously in 40 – 50% of the cases. Finally, the conclusions should rely on adequate statistical analysis which accounts for the influence of confounding variables in the evolution of this still mysterious hepato-neurological entity.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Reference
Adams R.D. and Foley J.M. (1953). The neurological disorder associated with liver disease, in Metabolic and Toxic Diseases of the Nervous System (Merritt H. and Hare C.C. eds), vol. 32, pp. 198–237, Williams and Wilkins, Baltimore, M.D.
Atterbury C.E., Maddrey W.C., and Conn H.O. (1978). Neomycin, sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled double blind clinical trial. Dig. Dis. Sci. 23, 398–406.
Balistreri W.F. and Schuber T.W.K. (1987). Liver disease in infancy and childhood in “Disease of the Liver” 6th Ed. (Schiff L. and Schiff E.R., eds), pp 1337–1426, Lippincott, Philadelphia, P.A.
Bismuth H., Samuel D., Gugeriheim J., Castaing D., Bernuau J., Rueff B and Benhamou J.P. (1987). Emergency liver transplantation for fulminant hepatitis. Ann. Intern. Med. 107, 337–341.
Butterworth R.F., Giguère J.F., Michaud J., Lavoie J., and Pomier-Layrargues G. (1987). Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem. Pathol. 6, 1–12.
Chu N.S., and Yang S.S. (1988). Portal-systemic encephalopathy: alterations in somatosensory and brainstem auditory evoked potentials. J. Neurol. Sci. 84, 41–50.
Conn H.O. (1977). Trail making and number-connection tests in the assessment of mental state in portal systemic encephalopathy. Am. J. Dig. Dis. 22, 541–550.
Dawson A.M., MacLaren J.M. and Sherlock S. (1957). Neomycin in the treatment of hepatic coma. Lancet 2, 1263–1268.
DerSimonian R, Charette B.A., McPeek B., and Mosteller F. (1982). Reporting on methods in clinical trials. New. Engl. J. Med. 306, 1332–1337.
Fisher J.E., and Baldessarini R.J. (1971). False neurotransmitters and hepatic failure. Lancet 2, 75–80.
Heredia D., Caballeria J., Arroyo, V., Ravelli G., and Rodès J. (1987). Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy. A controlled trial. J. Hepatol. 4:293–298.
McDermott W.V., and Adams R.D. (1954). Episodic stupor associated with an Eck fistula in the human with particular reference to the metabolism of ammonia. J. Clin. Invest. 33, 1–9.
Mendenhall C.L., Rauster S., Marshall L., and Weesner R. (1986). A new therapy for portal systemic encephalopathy. Am. J. Gastroenterol. 81, 540–543.
Michel H., Bories P., Aubin J.P., Pomier-Layrargues G., Bauret P., and Bellet-Herman H. (1985). Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients. Liver 5, 282–289.
Michel H., Solere M., Granier P., Cauvet J.P., Bali J.P. and Bellet-Herman H. (1980). Treatment of cirrhotic hepatic encephalopathy with L Dopa. A controlled trial. Gastroenterology 79, 207–211.
Morgan M.Y., and Hawley K.E. (1987). Lactitol vs lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind randomized trial. Hepatology 7, 1278–1284.
Morgan M.H., Read A.E., and Speller D.C. (1983). Treatment of hepatic encephalopathy with metronidazole. Gut 23, 1–7.
Mullen K.D., Martin J.V., Mendelson W.B., Bassett M.L. and Jones E.A. (1988). Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy. Lancet 1, 457–459.
Najarian J.S. and Harper H.A. (1956). A clinical study of the effect of arginine on blood ammonia. Am. J. Med. 21, 832–842.
Orlandi F., Freddara U., Candelaresi M.T., Morettini A., Corazza G.R., Di Simone A., Dubrilla G., and Cavallini G. (1981). Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy. A randomized clinical study. Dig. Dis. Sci. 26, 498–506.
Pirotte J., Guffen M., and Devos J. (1974). Comparative study of basal arterial ammonemia and of orally-induced hyperammonemia in chronic portal systemic encephalopathy treated with neomycin, lactulose and an association of neomycin and lactulose. Digestion 10, 435–444.
Reynolds T.B., Redeker A.G., and Davis P. (1958). A controlled study of the effects of L arginine on hepatic encephalopathy. Am. J. Med. 25, 359–367.
Sandford N.L., and Saul R.E. (1988). Assessment of hepatic encephalopathy with visual evoked potential compared with conventional methods. Hepatology 8, 1094–1098.
Schafer D.F., and Jones E.A. (1982). Hepatic encephalopathy and the gamma-aminobutyric acid neiirctransmitter system. Lancet 1, 18–19.
Simmons F., Goldstein H., and Boyle J.D. (1970). A controlled clinical trial of lactulose in hepatic encephalopathy. Gastroenterology 59, 827–832.
Tobe B.A. (1961). Observations on the use of L arginine and L glutamate in the treatment of hepatic encephalopathy. Can. Med. Assoc. J. 85, 591–603.
Zieve L., Doizaki W.M., and Zieve F.J. (1974). Synergism between mercaptans and ammonia or fatty acids in the production of coma: a possible role for mercaptans in the pathogenesis of hepatic coma. J. Lab. Clin. 83, 16–28.
Zieve L. (1982). Hepatic encephalopathy in Diseases of the Liver, 5th Ed (Schiff L., and Sniff E.R., eds) p. 433–459, Lippincott, Philadelphia, P.A.
Zieve L., Lyftogt C., and Raphael D. (1986). Ammonia toxicity: comparative protective effects of various arginine and ornithine derivatives, aspartate, benzoate and carbanyl glutamate. Metab. Brain Dis. 1, 25–35.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 The Humana Press Inc.
About this chapter
Cite this chapter
Layrargues, G.P., Giguère, JF., Lavoie, J., Butterwarth, R.F. (1989). Treatment of Hepatic Encephaiopathy. New Perspectives on Old Ideas.. In: Butterworth, R.F., Layrargues, G.P. (eds) Hepatic Encephalopathy. Experimental Biology and Medicine, vol 22. Humana Press. https://doi.org/10.1007/978-1-4612-4506-3_33
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4506-3_33
Publisher Name: Humana Press
Print ISBN: 978-1-4612-8851-0
Online ISBN: 978-1-4612-4506-3
eBook Packages: Springer Book Archive