Sunday 13 December 2009, 23:09

Hepatic encephalopathy: a common complication of liver diseases

Symptoms and pathogenesis of hepatic encephalopathy

Hepatic encephalopathy: a common complication of liver diseases

Hepatic encephalopathy (HE) is a clinical syndrome commonly associated with acute and chronic liver dysfunction. More precisely, it is a reversible neuropsychological disorder characterized by variable degrees of motor and cognitive deficits, resulting from the inability of the liver to remove toxins from blood.


Mild, subtle signs of hepatic encephalopathy (decreased attention, irritability, altered personality, reversal of day/night cycle) are found in 70% of patients affected with liver cirrhosis and may have a significant impact on patients’ quality of life and functional ability. More severe symptoms, observable in the late stages of liver disease, include myoclonus, seizures, delirium and coma.


Most of these signs and symptoms are manageable with proper treatment (lactulose as initial treatment and nonabsorbable antibiotics as second-line treatment) and can be reversed by liver transplantation.


The pathogenesis of hepatic encephalopathy has not been fully elucidated. The main pathogenetic factor seems to be an increase of ammonia in plasma and CNS (central nervous system), leading to alterations in neurotransmission. In normal physiological conditions the microbial gut flora produces an enzyme that releases ammonia from ingested proteins. Ammonia is then absorbed from the intestinal tract into the bloodstream and is transported to the liver, where it is converted into urea. In patients affected by hepatic cirrhosis, the filtering and detoxifying function of the liver is compromised: the result is a dramatic increase in blood and brain ammonia levels, leading to sensory and motor dysfunction.


Other factors have been implicated in the pathogenesis of HE. In patients affected with HE, there may be observed an increase in CNS levels of gamma aminobutyric acid (GABA, the main inhibitory neurotransmitter), endogenous benzodiazepine-like compounds, oxygen free radicals, nitric oxide and inflammatory cytokines. Other findings include a decrease in serum-levels of branched-chain amino acids and an increase in brain levels of aromatic amino acids.


All these factors may play a role in the pathogenesis of hepatic encephalopathy, although their exact  mechanisms have still to be established. Thus, the only certain statement we can make at this time is that hepatic encephalopathy is a complex neuropsychological disorder resulting from multiple factors (either independent or interdependent), rather than from a single pathophysiologic mechanism.


By Chiara De Carli

Category: Medical

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