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.
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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
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DOI: https://doi.org/10.1007/978-1-4612-4506-3_33
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