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Hepatic Encephalopathy: From Metabolic to Neurodegenerative

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Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transplanted patients. Several retrospective studies have shown that patients with a history of HE, particularly overt-HE, had persistent neurological complications even after liver transplantation (LT). These enduring neurological conditions significantly affect patient's quality of life and continue to add to the economic burden of chronic liver disease on health care systems. This review discusses the journey of the brain through the progression of liver disease, entering the invasive surgical procedure of LT and the conditions associated with the post-transplant period. In particular, it will discuss the vulnerability of the HE brain to peri-operative factors and post-LT conditions which may explain non-resolved neurological impairment following LT. In addition, the review will provide evidence; (i) supporting overt-HE impacts on neurological complications post-LT; (ii) that overt-HE leads to permanent neuronal injury and (iii) the pathophysiological role of ammonia toxicity on astrocyte and neuronal injury/damage. Together, these findings will provide new insights on the underlying mechanisms leading to neurological complications post-LT.

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Abbreviations

AT2A:

Alzheimer type II astrocytes

BBB:

Blood–brain barrier

BDL:

Bile-duct ligation

BDNF:

Brain-derived neurotrophic factor

CCl4 :

Carbon tetrachloride

cGMP:

Cyclic guanosine monophosphate

CLD:

Chronic liver disease

CNS:

Central nervous system

EEG:

Electroencephalogram

GS:

Glutamine synthetase

HE:

Hepatic encephalopathy

LT:

Liver transplantation

LTP:

Long-term potentiation

mHE:

Minimal HE

MRI:

Magnetic resonance imaging

NMDA:

N-Methyl-D-aspartate

PCA:

Portocaval anastomosis

TAA:

Thioacetamide

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Acknowledgements

The authors gratefully acknowledge the financial support of Canadian Institutes of Health Research (CIHR). Figures are created with BioRender.com.

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  1. Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, 900, rue Saint-Denis Pavillon R, R08.422, Montreal, QC, H2X-0A9, Canada

    Rafael Ochoa-Sanchez, Farzaneh Tamnanloo & Christopher F. Rose

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  1. Rafael Ochoa-Sanchez
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RO, FT, and CFR, contributed to the review concept and wrote the manuscript review.

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Ochoa-Sanchez, R., Tamnanloo, F. & Rose, C.F. Hepatic Encephalopathy: From Metabolic to Neurodegenerative. Neurochem Res 46, 2612–2625 (2021). https://doi.org/10.1007/s11064-021-03372-4

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