Hepatic encephalopathy

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released July 20, 1999; last updated July 7, 2019; expires July 7, 2022

This article includes discussion of hepatic encephalopathy and increased GABA neurotransmission. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Hepatic encephalopathy is a reversible brain disorder associated with liver disease or portosystemic shunts. It may be due to hepatotoxicity of drugs. Clinical manifestations vary from confusion, somnolence, and disorientation to stupor and coma. This article describes the diagnosis as well as management of the condition. Medical therapy may suffice in early and less severe cases, but severe acute hepatic failure may require liver transplantation. As an interim measure, cell therapy by transplantation of genetically modified hepatocytes or hematopoietic stem cells may reduce disease and extend survival until a donor becomes available for liver transplant or the patient's own liver recovers function.

Key points


• Hepatic encephalopathy is a potentially reversible metabolic disturbance of the brain in liver disease.


• The most common cause is cirrhosis of the liver, but other hepatotoxic agents may lead to hepatic encephalopathy.


• Manifestations of hepatic encephalopathy range from minimal cognitive deficits to stupor and coma.


• Most of the cases can be managed medically, but liver transplant is required in some cases.

Historical note and terminology

Hepatic encephalopathy is defined as a metabolically induced, potentially reversible functional disturbance of the brain that may occur in acute or chronic liver disease (Cash et al 2010). It is characterized by disturbances of consciousness and other neuropsychiatric manifestations, which are due to metabolic disturbances associated with liver disease or portosystemic shunts. The association between liver disease and mental disorders has been recognized since the time of Hippocrates (Chadwick and Mann 1950). Galen, the Roman physician of the 2nd century, described neurologic and psychiatric symptoms resulting not only from brain diseases but also from diseases of other organs, including the liver (Sherlock 1997). An oil painting by Rubens (1577 to 1640), The Drunken Silen, is exhibited in Munich, Germany, and shows characteristic symptoms of hepatic insufficiency. Morgagni, the father of pathologic anatomy, described the relation between liver failure and mental disorder in the 18th century (Morgagni 1769). The fourth case of his study may have been 1 of hepatic encephalopathy. In this case report, Morgagni described an alcoholic man with a history of abdominal pain and delirium who died in coma. Autopsy showed liver cirrhosis, but the brain was grossly normal. Further studies of hepatic encephalopathy continued in the 19th century. Hepatolenticular degeneration associated with cirrhosis of the liver was described in the early part of the 20th century and was later determined to be a hereditary disorder of copper metabolism (Wilson 1912). The classical works in which the modern concepts of hepatic encephalopathy are based were published in the 1950s (Adams and Foley 1953; Sherlock et al 1954).

Classification. A simplified classification of hepatic encephalopathy is as follows:

(1) Acute hepatic encephalopathy associated with acute liver failure and characterized by cerebral edema and raised intracranial pressure. This is likely to be manifested as hepatic coma.

(2) Subacute or subclinical hepatic encephalopathy associated with hepatic cirrhosis and associated with abnormal findings on neuropsychological testing.

(3) Chronic hepatic encephalopathy associated with hepatic cirrhosis. This classification of hepatic encephalopathy takes several forms. The most common form of presentation is "precipitant-induced encephalopathy" in which cirrhotic patients develop progressive changes of mental function with several precipitating factors. One type is called portal-systemic encephalopathy because of extensive portosystemic shunting or surgical portacaval shunt. Another form is hepatocerebral degeneration, wherein patients present with dementia and extrapyramidal disorders.

The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) consider hepatic encephalopathy to be a continuum ranging from unimpaired cognitive function with intact consciousness through coma and use a grading system of 1 to 3 and recommend classification according to the type of underlying disease, severity of manifestations, time course, and precipitating factors (Vilstrup et al 2014). Accordingly, 3 types of hepatic encephalopathy are traditionally differentiated according to the underlying cause: type A as an essential component of acute liver failure, type B as a consequence of porto-systemic shunts in the absence of liver dysfunction, and type C in patients with liver cirrhosis and porto-systemic bypass.

Patients with chronic hepatic encephalopathy may present with delirium. According to the 1994 DSM-IV criteria, delirium due to liver disease or portosystemic shunting belongs to the section on cognitive disorders because deficits of cognition are the primary symptoms of delirium. Prior to the development of predominant cognitive changes, the patients may be evaluated according to the presenting symptoms, which may be mood disorders, sleep disturbances, or personality changes. If cognitive impairment dominates without impairment of consciousness, the patient is considered to have dementia due to liver disease or portosystemic shunting.

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