[5] The underlying mechanism is believed to involve the buildup of ammonia in the blood, a substance that is normally removed by the liver.

[1] The mildest form of hepatic encephalopathy is difficult to detect clinically, but may be demonstrated on neuropsychological testing.

[8] The first stage of hepatic encephalopathy is characterised by an inverted sleep-wake pattern (sleeping by day, being awake at night).

[4] More severe forms of hepatic encephalopathy lead to a worsening level of consciousness, from lethargy to somnolence and eventually coma.

Coma and seizures represent the most advanced stage; cerebral edema (swelling of the brain tissue) leads to death.

In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately.

Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy").

This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex.

There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system and the energy supply to other brain cells is decreased.

[4][9] Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol.

Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure.

[4][9] The symptoms of hepatic encephalopathy may also arise from other conditions, such as bleeding in the brain and seizures (both of which are more common in chronic liver disease).

If there is ascites, a diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP).

[4] The severity of hepatic encephalopathy is graded with the West Haven Criteria; this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and dependence on therapy.

[16][18] This is still an important finding, as minimal encephalopathy has been demonstrated to impair quality of life and increase the risk of involvement in road traffic accidents.

[18] The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.

[22] Hepatic encephalopathy type B may arise in those who have undergone a TIPS procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms.

[10] In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management.

[19] In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy.

Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight.

[4][10] Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis.

[23] Side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea.

Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects.

[25] Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy.

The occurrence of hepatic encephalopathy in people with Wilson's disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant.

Many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, Giovanni Battista Morgagni (1682–1771) reported in 1761 that it was a progressive condition.

[29] The West Haven classification was formulated by Professor Harold Conn (1925–2011) and colleagues at Yale University while investigating the therapeutic efficacy of lactulose.