Hepatic encephalopathy (HE) refers to a complex neuro-psychiatric syndrome that is progressive but potentially reversible and presents as a complication of acute or chronic liver failure. HE significantly impacts the cognitive function direct and indirect mechanisms. The ammonium ion (NH4⁺) in the low millimolar range exerts direct effects on inhibitory and excitatory neurotransmitters through different mechanisms, inactivating chlorine (Cl^-) ejection from neurons, destroying the concentration gradient of this ion across the neuronal membrane and abolishing inhibitory postsynaptic potential results in behavior and personality as well as transient neurological symptoms and electroencephalographic abnormalities. Blood ammonia concentrations are consistently elevated in liver failure. Positron emission tomography (PET) with ¹³NH₃ revealed an increase in the percentage of cerebral metabolism of ammonia. A review included all randomized, controlled, double-blind, and humans’ studies that were published in indexed journals. Most of the cases (76%) were caused by excessive alcohol consumption. In cirrhotic patients, ammonia detoxification takes place less in the liver and more in the skeletal muscle and kidney. In liver, ammonia is converted to urea and then excreted through the kidneys and into the colon. In skeletal muscle and kidney, ammonia is converted to glutamine thus enzymatically removing the ammonia. In addition, astrocytes in the brain also play a role in detoxifying ammonia via glutamine synthetase, the increase in ammonia concentrations passing the blood–brain barrier results in increase in glutamine in the brain and this bring in more water into astrocytes. This swelling of astrocytes leads to cerebral edema and intracranial hypertension, ultimately resulting in neuronal dysfunction. L-ornithine L-aspartate (LOLA) is a substrate for the metabolism and conversion of ammonia to urea and glutamine. L-ornithine L-aspartate was administered parenterally in all the studies; the mean dose was 20 g/d (range 5-40 g/d) and the duration of treatment ranged from 24 h to 7 d.

As compared with compared with an osmotic laxative (oral lactulose) the accumulated number of days of hospitalization for patients who received LOLA was reduced by 40%. Encephalopathy recovery time was 4.32 d vs. 10.15 d, respectively, in patients who received LOLA than in those who received lactulose. The etiology of hepatic encephalopathy is multifactorial and depends not only on the increase in blood ammonia but also on a triggering mechanism (such as infection, bleeding or an electrolyte disorder). Hence, improved neuropsychiatric status and decreased serum levels of ammonia with a low prevalence of adverse effects (less than 5% electrolyte disorder) may encourage the replacement of the osmotic laxative with LOLA which indeed, will reduce the cost of treatment, duration hospital stay and the risk of nosocomial infection.

Source: Pérez Hernández, José Luis et al., Annals of hepatology vol. 10 Suppl 2 (2011): S66-9.