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Definition

Loss of brain function occurs when the liver is unable to remove toxins from the blood. This is called hepatic encephalopathy (HE). This problem may occur suddenly or it may develop slowly over time.

Causes

An important function of the liver is to make toxic substances in the body harmless. These substances may be made by the body (ammonia), or substances that you take in (medicines).

When the liver is damaged, these "poisons" can build up in the bloodstream and affect the function of the nervous system. The result may be HE.

HE can occur suddenly and you may become ill very quickly. Causes of HE may include:

• Hepatitis A or B infection (uncommon to occur this way)
• Blockage of blood supply to the liver
• Poisoning by different toxins or medicines
• Constipation
• Upper gastrointestinal bleeding

People with severe liver damage often suffer from HE. The end result of chronic liver damage is cirrhosis. Common causes of chronic liver disease are:

• Severe hepatitis B or C infection
• Alcohol abuse
• Autoimmune hepatitis
• Bile duct disorders
• Some medicines
• Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)

Once you have liver damage, episodes of worsening brain function may be triggered by:

• Loss of body fluids (dehydration)
• Eating too much protein
• Low blood potassium or sodium levels
• Bleeding in the intestines, stomach, or food pipe (esophagus)
• Infections
• Kidney problems
• Low oxygen levels in the body
• Shunt placement or complications
• Surgery
• Narcotic pain or sedative medicines

Disorders that can appear similar to HE may include:

• Alcohol intoxication
• Alcohol withdrawal
• Bleeding inside the skull (subdural hematoma)
• Brain disorder caused by lack of vitamin B1 (Wernicke-Korsakoff syndrome)

In some cases, HE is a short-term problem that can be corrected. It may also occur as part of a long-term (chronic) problem from liver disease that gets worse over time.

Symptoms

Symptoms of HE are graded on a scale of grades 1 to 4. They may begin slowly and worsen over time.

Early symptoms may be mild and include:

• Breath with a musty or sweet odor
• Changes in sleep patterns
• Changes in thinking
• Mild confusion
• Forgetfulness
• Personality or mood changes
• Poor concentration and judgment
• Worsening of handwriting or loss of other small hand movements

Severe symptoms may include:

• Abnormal movements or shaking of hands or arms
• Agitation, excitement, or seizures (occur rarely)
• Disorientation
• Drowsiness or confusion
• Behavior or personality changes
• Slurred speech
• Slowed or sluggish movement

People with HE can become unconscious, unresponsive, and possibly enter into a coma.

People are often not able to care for themselves because of these symptoms.

Exams and Tests

Signs of nervous system changes may include:

• Shaking of the hands ("flapping tremor" or asterixis) when trying to hold arms in front of the body and lift the hands
• Problems with thinking and doing mental tasks
• Signs of liver disease, such as yellow skin and eyes (jaundice) and fluid collection in the abdomen (ascites)
• Musty odor to the breath and urine

Tests done may include:

• Complete blood count or hematocrit to check for anemia
• CT scan of the head or MRI
• EEG
• Liver function tests
• Prothrombin time
• Serum ammonia level in the blood 
• Sodium level in the blood
• Potassium level in the blood
• BUN (blood urea nitrogen) and blood creatinine to see how the kidneys are working

Treatment

Treatment of HE depends upon the cause.

If changes in brain function are severe, a hospital stay may be needed.

• Bleeding in the digestive tract must be stopped.
• Infections, kidney failure, and changes in sodium and potassium levels need to be treated.

Medicines are given to help lower ammonia level and improve brain function. Medicines given may include:

• Lactulose to prevent bacteria in the intestines from creating ammonia. It may cause diarrhea.
• Neomycin and rifaximin also reduce the amount of ammonia made in the intestines.
• If the HE improves while taking rifaximin, it should be continued indefinitely.

You should avoid:

• Any sedatives, tranquilizers, and any other medicines that are broken down by the liver
• Medicines containing ammonium (including certain antacids)

Your health care provider may suggest other medicines and treatments. These may have varying results.

Outlook (Prognosis)

The outlook of HE depends on the management of the cause of HE. Chronic forms of the disorder often continue to get worse and come back.

The first two stages of the disease have a good prognosis. Stage three and four have a poor prognosis.

When to Contact a Medical Professional

Contact your provider if you or people around you notice any problems with your mental state or nervous system function. This is important for people who already have a liver disorder. HE can get worse quickly and become an emergency condition.

Prevention

Treating liver problems may prevent HE. Avoiding alcohol and intravenous drugs can prevent many liver disorders.

References

Cameron J. Portal hypertension. In: Cameron J, ed. Current Surgical Therapy. 14th ed. Philadelphia, PA: Elsevier; 2023:413-456.

Garcia-Tsao G. Cirrhosis and its sequelae. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 139.

Mehta SS, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and other systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed. Philadelphia, PA: Elsevier; 2021:chap 94.

Wong MP, Moitra VK. Hepatic encephalopathy. In: Fleisher LA, Roizen MF, Roizen JD, eds. Essence of Anesthesia Practice. 4th ed. Philadelphia, PA: Elsevier; 2018:198-198.

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