The Neurobiology of Hepatic Encephalopathy

Abstract

Despite significant recent breakthroughs, with rapid discoveries provided by the twentieth century, hepatic encephalopathy remains an ancestral enigma that accompanies the history of mankind. Much of this is due to the reductionist view that a single process would have primacy over others, with the emphasis on hyperammonemic theory being its greatest example. Since other factors, such as the intestinal microbiota composition, the synergism with neuroinflammation, and the role of glutamatergic and GABAergic tonus balance have been discovered, it has become clear that the traditional and linear view of scientific research allows the understanding of the initial state of multiple dysfunctional systems, but is unable to predict the overall behavior of the disease. As consequence, there is a lack of innovative interventions for controlled clinical trials, making its therapeutic management very limited. The objective of this chapter is to provide a general theoretical overview of the most relevant hypotheses and findings in the neurobiology of hepatic encephalopathy, and how its toxic, metabolic and immunological alterations affect the cellular metabolism and neurotransmission dynamics, causing its characteristic cognitive and motor manifestations.