Branched-Chain Amino Acids in the Treatment of Severe Hepatic Encephalopathy

The most characteristic feature of the plasma amino acid (AA) profile in chronic liver failure is the rise in the three aromatic AA (AAA), phenylalanine (PHE), tyrosine (TYR) and free tryptophan (F. TRY) and the fall in the three branched-chain AA (BCAA), valine (VAL) leucine (LEU) and isoleucine (ILEU).1,2 These alterations of plasma AA are in turn responsible for brain accumulation of AAA. In fact, blood-brain entry of AAA is increased either because of a decreased competition by BCAA which use the same transport system across the blood-brain-barrier (BBB)3 or because an increased activity of the transport system itself.4,5 Brain accumulation of AAA may profoundly alter the synthesis of neurotransmitters leading to a depletion of putative neurotransmitters, norepinephrine and dopamine, and an accumulation of false neurotransmitters (such as octopamine and phenylethanolamine)6,7,8 or inhibitory neurotransmitters (such as serotonin).9 The false neurotransmitters hypothesis offers an appealing explanation for the neurologic disorders and coma that complicate chronic liver failure.