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Neuronal cell death in hepatic encephalopathy

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Abstract

It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian) hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy and cerebellar degeneration. In addition, there is evidence to suggest that liver failure contributes to the severity of neuronal loss in Wernicke’s encephalopathy. The long-standing nature of the thalamic and cerebellar lesions, over 80% of which are missed by routine clinical evaluation, together with the probability that they are nutritional in origin, underscores the need for careful nutritional management (adequate dietary protein, Vitamin B1) in liver failure patients. Mechanisms identified with the potential to cause neuronal cell death in liver failure include NMDA receptor-mediated excitotoxicity, lactic acidosis, oxidative/nitrosative stress and the presence of pro-inflammatory cytokines. The extent of neuronal damage in liver failure may be attenuated by compensatory mechanisms that include down-regulation of NMDA receptors, hypothermia and the presence of neuroprotective steroids such as allopregnanolone. These findings suggest that some of the purported “sequelae” of liver transplantation (gait ataxia, memory loss, confusion) could reflect preexisting neuropathology.

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Acknowledgements

Studies from the author’s research unit were made possible by funding from the Canadian Institutes of Health Research and The Canadian Association from the Study of the Liver (CASL).

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  1. Neuroscience Research Unit, Hôpital Saint-Luc (CHUM), 1058 Saint-Denis, Montréal, Quebec, Canada, H2X 3J4

    Roger F. Butterworth

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Correspondence to Roger F. Butterworth.

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F. Butterworth, R. Neuronal cell death in hepatic encephalopathy. Metab Brain Dis 22, 309–320 (2007). https://doi.org/10.1007/s11011-007-9072-3

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