According to this classification, hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause. Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema
Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease
Type C (=cirrhosis) occurs in people with cirrhosis - this type is subdivided in episodic, persistent and minimal encephalopathyThe term minimal encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction, but can be demonstrated with neuropsychological studies. 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. Minimal HE
The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test". In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and PSE-Syndrom-Test may be used for this purpose. The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.
There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type.Despite numerous studies demonstrating the central role of ammonia, ammonia levels do not always correlate with the severity of the encephalopathy; it is suspected that this means that more ammonia has already been absorbed into the brain in those with severe symptoms whose serum levels are relatively low. Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol.Numerous other abnormalities have been described in hepatic encephalopathy, although their relative contribution to the disease state is uncertain. Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure. Benzodiazepine-like compounds have been detected at increased levels as well as abnormalities in the GABA neurotransmission system. An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role. Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes.