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Hepatic Encephalopathy

What is hepatic encephalopathy?

Hepatic encephalopathy (HE) is a disorder of mental activity, neuromuscular function and consciousness that occurs as a result of either chronic or acute liver failure. This complex neuropsychiatric syndrome is primarily caused by metabolic abnormalities. The syndrome may occur spontaneously or be induced by some precipitating factor and may be reversible, either by improvement in liver function, correction of the precipitating factors or the administration of therapy. However, HE can eventually lead to coma and especially in acute liver failure, may be fatal.

What are the different types of hepatic encephalopathy?

  1. Acute or subacute encephalopathy - is generally rapidly progressive over the short course and is a complication of acute liver disease. This type of HE most often occurs in patients with acute fulminant viral hepatitis, toxic hepatitis and Reye's syndrome and is a sign of terminal liver failure.

  2. Acute or subacute recurrent encephalopathy - more than one episode of HE in a patient with chronic disease with cirrhosis, with periods in between without any observable HE. Specific precipitating factors can usually be identified in association with the recurrent episodes. Even though coma may develop, it is rarely fatal.

  3. Chronic recurrent encephalopathy - multiple recurrences of observable HE, requiring continuous therapy to decrease or prevent the development of symptoms during intervening periods. Usually this type of HE is found in patients who are cirrhotic with an extensive portal collateral circulation with shunts either surgical or spontaneously evolving.

  4. Chronic permanent encephalopathy or myelopathy - permanent neurological abnormalities unresponsive to therapy and forming part of the spectrum of acquired hepatocerebral degeneration and may include a myelopathy. This condition is very rare.

What are the symptoms of hepatic encephalopathy?

There are four different stages of symptoms that can occur. The abnormalities that reflect mental and personality changes are distinguished from those reflecting neuromuscular functions.

In Stage 1, the symptoms include mild confusion, short attention span, nightmares and poor night time sleep with daytime sleepiness, restlessness, depression, aimless wandering, anxiety and irritability.

In Stage 2, the mental and personality changes include obvious drowsiness, obvious personalty change, gross impairment of ability to do mental tasks, slow response, disobedience, sullenness and disorientation for time and place.

In Stage 3, the symptoms include bizarre behaviour, occasional fits of rage, confusion, speech that is incomprehensible, paranoia and anger.

In Stage 4, coma is either responsive or unresponsive.

How is hepatic encephalopathy diagnosed?

The diagnosis of HE is made primarily by recognition of neuropsychiatric changes occurring in a patient with known liver disease. In a patient with cirrhosis, whose liver disease has been followed for some time, the diagnosis becomes readily apparent with development of several of the symptoms mentioned above. When confronted with a patient who presents with an encephalopathy or a patient known to have a history of previous or current liver disease and who has neurological impairment, it is very important that attention should be paid to neurological symptoms such as personality changes, hypersomnia, reversal of sleep pattern, presence of precipitating factors such as gastrointestinal bleeding, use of sedative hypnotic drugs, etc. The presence of a flapping tremor is also an important physical finding in a patient with HE. There is no specific diagnostic test, improvement with treatment is the usual method of diagnosis.

What is the pathogenesis of hepatic encephalopathy?

The precise pathogenesis of hepatic encephalopathy still remains unknown. However, a number of substances or mechanisms have been implicated. These substances include ammonia, mercaptans, free fatty acids, amino acid imbalance, altered GABA neurotransmission, other neurotransmitter changes, synaptic plasma membrane changes and false neurotransmitters. The disorders that occur when the liver fails are so complex that it is conceivable (and quite likely) that HE results from the complicated interplay of many of the factors mentioned above.

What is the treatment for hepatic encephalopathy?

The most important aspect of management is the prompt recognition and correction of precipitating factors, when possible. These factors include kidney failure, use of sedatives or narcotics, GI bleeding, hypokalemia/alkalosis, dietary protein increase, infection, constipation and exacerbation of liver disease. The importance of recognizing and correcting any precipitating factors in patients with HE cannot be overemphasized.

Every patient with alcoholic cirrhosis and presumed HE should receive thiamine upon admission to hospital. Additional therapeutic measures include dietary protein restriction and lactulose and occasionally additional neomycin or metronidazole therapy. 

The use of L-Dopa or bromocriptine is reserved for patients who do not respond to more conventional therapies, even though, in general, these two therapies are not effective in most patients. Patients with chronic encephalopathy are encouraged to eat vegetable rather than animal protein.

Branched-chain amino acid (BCAA) therapy, administered either orally or intravenously, remains the most controversial treatment. Available data about BCAA are conflicting and do not support its routine use.

Newer therapies include lactilol, a disaccharide compound quite similar to lactulose. It is reported to be as effective as lactulose or neomycin but is associated with a decreased incidence of severe diarrhea and other side effects. In many patients with chronic liver disease, liver transplantation entirely reverses HE. Thus, liver transplantation may be considered in some patients with hepatic encephalopathy.