Hepatic Encephalopathy

Hepatic disease may lead to symptoms of brain malfunction or encephalopathy ranging from subtle behavioral changes to deep coma (see Chapter 55 ). Such patients often have shunting of blood around the liver, produced surgically or occurring spontaneously. Increases in brain

2916

In the case of catecholamines, the excess precursor material in the brain in hepatic encephalopathy may cause inhibition of the normal synthetic pathway, leading to a reduced content of dopamine and norepinephrine and to increased amounts of trace amines, such as octopamine and phenylethanolamine.

Plasma amino acid profiles are characteristically changed when hepatic failure is present. A common finding is elevation of phenylalanine and methionine levels. The plasma levels of the branched-chain amino acids leucine, isoleucine, and valine are generally decreased in patients with hepatic failure, possibly because of peripheral use of these amino acids in muscle. The levels of plasma amino acids in liver disease relate to competition between some of the same neutral amino acids—phenylalanine, tyrosine, and tryptophan—and of the branched-chain amino acids in penetrating the blood-brain barrier. The neurotransmitter profile is markedly deranged in hepatic encephalopathy. There is increased serotonin, decreased norepinephrine, and to a lesser extent, decreased dopamine in the brain. The level of octopamine, a known false transmitter that may replace dopamine and norepinephrine in the central nervous system, is markedly increased in the brains of animals and in the blood of patients in hepatic coma.

Tyrosine is thought to be the normal precursor of the catecholamines dopamine and norepinephrine. Profound depletion of norepinephrine has been demonstrated in hepatic coma.^[210] Phenylalanine may compete with tyrosine-3- hydroxylase and decrease the conversion of tyrosine to dopa in hepatic encephalopathy. Tyrosine accumulates and becomes decarboxylated to tyramine and then to octopamine.

Aims of Nutritional Support in Liver Failure

If the amino acid levels in plasma are abnormal in patients with hepatic encephalopathy, and if these have a role in the pathophysiology of the disease, a reasonable starting point in therapy is normalization of the plasma amino acid patterns (see Chapter 54 and Chapter 55 ). Therapeutic efforts have been directed at attempting to normalize the brain amino acid concentrations during nutrition support with specific "hepatic failure" solutions. The amino acids tryptophan, tyrosine, and phenylalanine compete with other large neutral amino acids (including the branched-chain amino acids) for passage across the blood-brain barrier. There has been increasing interest in therapeutically altering plasma amino acid concentrations in patients with liver disease by infusing branched-chain amino acid mixtures. The results obtained with these treatments have been ambiguous. Several uncontrolled studies have reported clinical improvement.^[211] Controlled studies have not clarified these situations. For example, Wahren and coworkers^[212] concluded that no effect on encephalopathy could be attributed to the amino acid infusion.

An experimental solution has been developed that appears to be well tolerated by patients with hepatic insufficiency and encephalopathy.^[213] The solution is commercially available as HepatAmine. The solution with reduced aromatic amino acids and increased amounts of branched-chain amino acids was devised to normalize plasma amino acid patterns and to improve encephalopathy. However, standard nutritional support solutions, using reduced protein loads, also appear to work well in treating patients with hepatic failure.