Department of Surgery, School of Medicine, Complutense University of Madrid, Madrid, Spain.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
INEUROPA (Instituto de Neurociencias del Principado de Asturias), Oviedo, Spain.
Department of Physiology, School of Medicine, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (Idi PAZ), Autonoma University of Madrid, Madrid, Spain.
Laboratory of Neuroscience, Department of Psychology, University of Oviedo, Asturias, Spain.
Hepatic encephalopathy is a severe complication of both chronic and acute liver diseases. The term hepatic encephalopathystems from the belief that hepatic insufficiency is its fundamental etiopathogenic factor. However, most clinical cases show liver failure along with mesenteric venous portal hypertension. This portal hypertension would explain the abnormal mechanical forces suffered by the digestive tract in the early stages of the disorder. These forces could regulate some gut biochemical pathological pathways in a process known as mechanotransduction. Thus, portal hypertension would begin with the establishment of a mechanotransduced afferent or sensory inflammatory gut-brain pathway, resulting in functional and structural changes in the central nervous system. In this review, we will revisit the term "hepatic encephalopathy" in light of new results where portal hypertension occurs before liver failure and is accompanied by brain changes. Moreover, we will point out cellular links that can explain the microbiota, immune, gut, and brain axis disturbances found in this disorder.