<p>Several studies have elucidated that toxic levels of ammonia in the brain are one of the more prominent features, although the pathophysiology of he is still not fully understood. [7] A healthy liver is able to maintain blood ammonia levels at low levels of 35-50 uM through the urea cycle. However, in cirrhosis, factors and other molecules (e.g., ammonia) that are normally prevented by the body from crossing the blood-brain barrier are able to naturally cross the blood-brain barrier, fill the brain, and stimulate pathophysiological pathways that can have deleterious effects. Neurological damage and cognitive decline due to liver dysfunction are the result of blood-borne factors that affect blood-brain barrier permeability and/or alter blood-brain barrier integrity.[8]</p>
<p>The conduction of nerve impulses is accomplished by means of transmitters. There are two types of neurotransmitters, excitatory and inhibitory, which maintain a physiological balance when normal. Among them, inhibitory neurotransmitters are formed only in the brain. Aromatic amino acids in food, such as tyrosine and phenylpropanoid amino acids, are converted to tyramine and phenylethylamine PEA, respectively, by the action of the decarboxylase enzyme of enterobacteria.</p>
<p>Normally, these two amines are cleared by monoamine oxidase in the liver, but when liver failure occurs, clearance is impaired, and these two amines can enter the brain tissue, where they are formed into amines (β-hydroxytyramine) and phenylethanolamine, respectively, by β-hydroxylase. The latter two are similar in chemical structure to the normal neurotransmitter norepinephrine, but are unable to transmit nerve impulses or have very weak effects, and are therefore called pseudoneurotransmitters. When pseudoneurotransmitters are taken up by brain cells and replace normal transmitters in the synapses, nerve conduction is impaired, and excitatory impulses are not transmitted normally to the cerebral cortex, resulting in abnormal inhibition; impaired consciousness and coma occur. []</p>
<p>In an effort to find out more precisely what risk factors are associated with the development of HE, our team actively communicated with the PI and learned of a related, unpublished study that concluded that patients with higher baseline PEA levels (upper quartile) had a 6.95-fold higher risk of developing HE at 3 months than patients in the lower quartile (p = 0.0017) [].</p>
<p>Normally, these two amines are cleared by monoamine oxidase in the liver, but when liver failure occurs, clearance is impaired, and these two amines can enter the brain tissue, where they are formed into amines (β-hydroxytyramine) and phenylethanolamine, respectively, by β-hydroxylase. The latter two are similar in chemical structure to the normal neurotransmitter norepinephrine, but are unable to transmit nerve impulses or have very weak effects, and are therefore called pseudoneurotransmitters. When pseudoneurotransmitters are taken up by brain cells and replace normal transmitters in the synapses, nerve conduction is impaired, and excitatory impulses are not transmitted normally to the cerebral cortex, resulting in abnormal inhibition; impaired consciousness and coma occur. </p>
<p>In an effort to find out more precisely what risk factors are associated with the development of HE, our team actively communicated with the PI and learned of a related, unpublished study that concluded that patients with higher baseline PEA levels (upper quartile) had a 6.95-fold higher risk of developing HE at 3 months than patients in the lower quartile (p = 0.0017) .</p>
<h3>Current treatments</h3>
<p>Given the specificity of ammonia in the diagnosis and treatment of HE, the general pharmacological approach to HE is broadly directed towards ammonia.</p>
