Hepatic Encephalopathy

How hepatic encephalopathy happens

The gut produces ammonia and other toxins when bacteria break down protein. Normally the liver removes these before they reach the rest of the body. In cirrhosis the damaged liver clears them poorly, and high pressure in the portal vein (portal hypertension) diverts blood around the liver through shunts. Ammonia reaches the brain, where it causes swelling of support cells (astrocytes), changes nerve signaling and makes the brain sleepy and confused. Inflammation from infection makes this worse.

Doctors describe three kinds:

• Type A: from sudden (acute) liver failure, for example from acetaminophen overdose or acute hepatitis. Brain swelling can be life-threatening.
• Type B: from a portosystemic bypass (shunt) without liver disease. Rare.
• Type C: from cirrhosis. This is by far the most common.

Hepatic encephalopathy symptoms

Symptoms can come on over hours or days, or be present at a low level for a long time.

• forgetfulness, poor concentration and slowed thinking
• sleeping during the day and awake at night (reversed sleep pattern)
• mood changes, irritability, anxiety, apathy or inappropriate behavior
• confusion about time, place or people
• a flapping tremor of the hands when the arms are held out with wrists bent back (asterixis)
• slurred speech, clumsiness and poor handwriting
• a sweet, musty breath odor (fetor hepaticus)
• drowsiness, stupor and, in severe cases, coma

Other signs of liver disease are often present: jaundice, a swollen belly from fluid (ascites), easy bruising and spider veins.

Hepatic encephalopathy stages: symptoms chart

Doctors grade severity using the West Haven criteria.

Minimal and grade 1 are grouped as covert hepatic encephalopathy. Grades 2 to 4 are overt.

Common triggers

Most episodes of overt hepatic encephalopathy in cirrhosis have a trigger that can be found and treated:

• infections, including spontaneous bacterial peritonitis, urinary infections and pneumonia
• bleeding in the gut, often from esophageal varices, because blood in the gut is a large protein load
• constipation
• dehydration, overuse of diuretics, vomiting or diarrhea
• low potassium or sodium
• sedatives, sleeping pills, opioids and some antihistamines
• alcohol
• kidney injury
• a TIPS procedure (a shunt placed to treat portal hypertension)

Diagnosis

There is no single test. Hepatic encephalopathy is diagnosed by finding brain dysfunction in someone with liver disease after excluding other causes. Doctors:

• examine for confusion and asterixis and grade the severity
• look for triggers with blood counts, kidney function, electrolytes, blood sugar, blood and urine cultures, and a sample of belly fluid if ascites is present
• check for other causes of confusion, such as low blood sugar, alcohol withdrawal, Wernicke encephalopathy, head injury and drug toxicity
• may measure blood ammonia. A normal level makes HE less likely, but a high level alone does not prove it
• may order a CT scan of the head, particularly after a fall
• use psychometric tests to detect minimal HE

Treatment

Treat the trigger

Antibiotics for infection, stopping bleeding, correcting fluids and salts, relieving constipation, and stopping sedatives and alcohol.

Lactulose

Lactulose is a syrup sugar that works in the bowel. It draws ammonia into the gut, changes gut bacteria and causes loose stools that carry toxins out. The dose is adjusted to produce 2 to 3 soft bowel movements a day. It is the first-line treatment and is continued long term after an episode to prevent recurrence. Polyethylene glycol is sometimes used instead in hospital.

Rifaximin

An antibiotic that stays mostly in the gut and reduces ammonia-producing bacteria. It is added to lactulose after a recurrence and reduces readmissions to hospital.

Nutrition

Protein should not be restricted. People with cirrhosis need adequate protein (about 1.2 to 1.5 g per kg of body weight a day) and frequent small meals with a late-evening snack to avoid muscle loss. Vegetable and dairy protein may be better tolerated.

Severe cases

Grade 3 or 4 encephalopathy needs hospital and sometimes intensive care, with airway protection. Recurrent or persistent HE is an indication to be assessed for liver transplantation, which cures it.

Outlook and living with it

An episode of overt hepatic encephalopathy marks advanced liver disease and signals a shorter outlook without transplant. Many people recover fully from individual episodes with treatment, but some memory and attention problems can persist. Covert HE affects driving, so people with cirrhosis should discuss whether driving is safe. Family members are often the first to notice early signs such as day-night sleep reversal, and should know to act on them.

Frequently asked questions

What are the first symptoms of hepatic encephalopathy?

Early signs are subtle: forgetfulness, poor concentration, mood or personality change, and sleeping in the day while being awake at night. Family members often notice these before the person does. A shaky, flapping tremor of the outstretched hands is a characteristic early physical sign.

What are the stages of hepatic encephalopathy?

Doctors use the West Haven grades. Minimal HE shows only on special tests. Grade 1 causes mild confusion and sleep problems. Grade 2 adds lethargy, disorientation and a flapping tremor. Grade 3 causes marked confusion and drowsiness. Grade 4 is coma.

Can hepatic encephalopathy be reversed?

Often, yes. Most episodes improve within days once the trigger is treated and lactulose is started. However, it tends to recur while the liver remains damaged, and repeated episodes can leave some lasting thinking problems. A liver transplant can cure it.

Why is lactulose used for hepatic encephalopathy?

Lactulose traps ammonia in the bowel and speeds its removal in loose stools. The aim is 2 to 3 soft bowel movements a day. Skipping lactulose or becoming constipated is a common reason for symptoms to return, so it should be taken consistently.

Should people with hepatic encephalopathy avoid protein?

No. Current guidelines advise against restricting protein. People with cirrhosis need adequate protein to prevent muscle loss, which itself worsens ammonia handling. Eating small meals through the day and a bedtime snack is recommended.