Hepatic encephalopathy (HE) or portosystemic encephalopathy (PSE)

The pathophysiology of hepatic encephalopathy is complex. Often many different mechanisms contribute to the neurological decline in patients with liver disease: metabolic encephalopathy, brain atrophy or edema, or a mixture of all of these factors. The metabolic encephalopathy is mostly caused by increased ammonia levels which causes an inflow of certain amino acids to the brain, affecting the synthesis of neurotransmitters. Ammonia may also affect the electric activity of neurons and increase the osmolality of astrocytes, causing brain edema. The end result of these complex metabolic abnormality is the activation of inhibitory pathways (mostly related to GABA) and the suppression of excitatory pathways (related to glutamate and cathecolamines).

CAUSES:

Any cause of liver disease (multiple etiologies such as infection, autoimmune, drugs, alcoholism)

Portal-systemic shunts

Precipitating factors include:

Constipation
Gastrointestinal bleeding
Infection (SBP or UTI)
Hypokalemia
Metabolic alkalosis
Renal failure
Hypovolemia
Hypoxia
Hypnotic use
Hypoglycemia
Cancer
Thrombosis of hepatic or portal vein

SIGNS & SYMPTOMS:

The symptoms may affect consciousness, intellectual function, behavior or the neuromuscular system. Particular changes may include:

Impaired attention, delayed reaction time and memory loss
Sleep disorders (insomnia or hypersomnia)
Movement disorders: Asterixis, Bradykinesia, Myoclonus

TYPES AND GRADES:

Hepatic encephalopathy may be classified in 4 different ways.

It can be classified according to the symptoms in different grades.

Grade 0 – Minimal hepatic encephalopathy (also known as CHE and previously known subclinical hepatic encephalopathy); lack of detectable changes in personality or behavior; minimal changes in memory, concentration, intellectual function, and coordination; asterixis is absent.
Grade 1 – Trivial lack of awareness; shortened attention span; impaired addition or subtraction; hypersomnia, insomnia, or inversion of sleep pattern; euphoria, depression, or irritability; mild confusion; slowing of ability to perform mental tasks
Grade 2 – Lethargy or apathy; disorientation; inappropriate behavior; slurred speech; obvious asterixis; drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time
Grade 3 – Somnolent but can be aroused; unable to perform mental tasks; disorientation about time and place; marked confusion; amnesia; occasional fits of rage; present but incomprehensible speech
Grade 4 – Coma with or without response to painful stimuli

It may also be classified according to the underlying disease:

Type A: Resulting from acute liver failure
Type B: Resulting from portosystemic shunting
Type C: Resulting from cirrhosis

It can also be classified according to the time course:

Episodic HE
Recurrent HE (<6 months between episodes)
Persistent HE (changes that are always present)

Finally, it may be classified regarding the presence or absence of a trigger:

Precipitated
Nonprecipitated

DIAGNOSIS:

The diagnosis is mostly clinical and should be considered when there is no other obvious cause of neurological dysfunction (change in the behavior/cognition/consciousness) in a patient with liver disease.

The onset of disorientation or asterixis characterizes hepatic encephalopathy. Some patients may have subtle findings often only identified by specialized tests, a condition called minimal hepatic encephalopathy.

Patients with hepatic encephalopathy usually have alterations in their bilirubin, albumin and PT/INR due to the underlying liver disease.

Ammonia levels may be elevated, but elevated levels are not necessarily required to establish the diagnosis.

TREATMENT:

Patients with mild hepatic encephalopathy may be managed outpatient, whereas patients with more prominent altered mental status may need hospital admission.

Precipitating causes (infection, thrombosis, medications, hypoxia, electrolyte abnormalities) should be identified and managed as soon as possible.

Protein should not be removed from the diet (removal increases mortality). If animal protein worsens the symptoms, vegetable protein may be used as a substitute.

The treatment for the encephalopathy itself involves reducing the ammonia levels in the blood. This can be done through the use of lactulose (20-40g/day, divided in 3-4 doses to produce 2-3 bowel movements), lactiol or rifamixin (400mg PO TID or 550mg PO BID). Other treatments that exist include neomycin (not first line), branched-chain amino acids (BCAA) and ornithine-aspartate.

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