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Neuroactive amino acids in hepatic encephalopathy

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Abstract

There is abundant evidence to suggest that alterations of excitatory and inhibitory amino acids play a significant role in the pathogenesis of hepatic encephalopathy (HE) in both acute and chronic liver diseases. Brain glutamate concentrations are reduced in patients who died in hepatic coma as well as in experimental HE, astrocytic reuptake of glutamate is compromised in liver failure and postsynaptic glutamate receptors (both NMDA and non-NMDA subclasses) are concomitantly reduced in density. Recent studies in experimental acute liver failure suggest reduced capacity of the astrocytic glutamate transporter in this condition. Together, this data suggests that neuron-astrocytic trafficking of glutamate is impaired in HE. Other significant alterations of neuroactive amino acids in HE include a loss of taurine from brain cells to extracellular space, a phenomenon which could relate both to HE and to brain edema in acute liver failure. Increased concentrations of benzodiazepine-like compounds have been reported in human and experimental HE. Clinical trials with the benzodiazepine antagonist flumazenil reveal a beneficial effect in some patients with HE; the mechanism responsible for this effect, however, remains to be determined.

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  1. Neuroscience Research Unit, Hôpital Saint-Luc, 1058 St-Denis Street, H2X 3J4, Montreal, Québec, Canada

    Roger F. Butterworth

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Butterworth, R.F. Neuroactive amino acids in hepatic encephalopathy. Metab Brain Dis 11, 165–173 (1996). https://doi.org/10.1007/BF02069503

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