Hepatic encephalopathy

Hepatic encephalopathy is a serious brain disorder that occurs when a damaged liver can no longer remove toxins from the blood, causing confusion, personality changes, and impaired thinking that can progress to coma or death without treatment.

Table of contents

• What is hepatic encephalopathy?
• Other names for this condition
• Body parts affected
• Types of hepatic encephalopathy
• How hepatic encephalopathy develops
• Signs and symptoms
• Grading system
• Common triggers
• How it is diagnosed
• Treatment approaches
• What to expect
• Information for caregivers

What is hepatic encephalopathy?

Hepatic encephalopathy is brain dysfunction caused by liver dysfunction. The word “encephalopathy” means brain dysfunction, and “hepatic” means related to the liver^[1].

This condition affects your central nervous system (the brain and spinal cord) and changes how you think, feel, and act. It happens when your liver cannot filter harmful substances called toxins (poisonous substances) from your blood as it normally should. When these toxins build up in your bloodstream and reach your brain, they can damage nerve cells and the supporting cells in your brain^[1][9].

Hepatic encephalopathy usually develops in people with advanced liver disease, especially when liver functions begin to fail. Up to 4 out of 5 people living with cirrhosis (severe scarring of the liver) may eventually develop some form of hepatic encephalopathy^[4][5].

portosystemic encephalopathy, HE

Body parts affected

• Brain
• Liver
• Blood vessels
• Intestines

Types of hepatic encephalopathy

Healthcare providers classify hepatic encephalopathy into three main types based on what causes it^[2][7]:

Type A results from acute liver failure, which is a sudden and severe loss of liver function that happens quickly, within days or weeks. This is a unique and highly serious situation.

Type B happens when blood that should flow through the liver instead bypasses it through an abnormal connection called a portosystemic shunt. In these cases, there is no major liver disease, but toxins are not being filtered because blood is not reaching the liver properly.

Type C occurs in people who have cirrhosis or chronic liver failure. This is the most common type and can be further described as happening suddenly (acute), lasting a long time (chronic), or coming and going in episodes.

How hepatic encephalopathy develops

Your liver plays a vital role in keeping your body healthy. It removes toxic substances from your blood, including harmful compounds produced in your intestines and other organs. When your liver becomes severely damaged, the number of working liver cells decreases, and some blood may be diverted around the liver before toxins are removed. This is called portal-systemic shunting^[9].

One of the main toxins that builds up is ammonia, which is formed by bacteria in your intestines as they break down proteins. Normally, your liver processes and removes ammonia from your blood. In people with advanced liver disease, ammonia accumulates and affects brain cells called astrocytes, which are supporting cells for nerve cells. This accumulation changes the chemistry inside your brain and disrupts normal brain function^[8][9].

Another substance that can accumulate is manganese, a metal that can be deposited in certain brain areas and may cause structural changes that contribute to symptoms^[9].

Many conditions can damage your liver enough to cause hepatic encephalopathy. The most common underlying liver diseases include^[2]:

• Cirrhosis from chronic alcohol use
• Chronic hepatitis C or hepatitis B (viral infections that damage the liver over many years)
• Metabolic dysfunction-associated steatohepatitis, previously known as NASH (severe inflammation caused by excess fat in the liver)
• Autoimmune liver diseases (conditions where the immune system attacks the liver)

Signs and symptoms

Hepatic encephalopathy can show up in many different ways. Not everyone will have every symptom. The condition can affect your^[1]:

• Mood and personality
• Behavior and impulse control
• Memory, concentration, and thinking
• Consciousness and sleep patterns
• Coordination and motor functions
• Ability to care for yourself

Symptoms may appear suddenly or develop gradually. They may be steady and lasting, or they may come and go in episodes. They can get better or worse depending on your overall health condition^[1].

Early signs that you or someone close to you might notice include subtle changes in short-term memory, concentration, mood swings such as anxiety or unusual happiness, and difficulty with tasks that require fine movements like writing^[1][5].

As the condition progresses, symptoms become more obvious and may include clear personality changes, inappropriate or out-of-character behaviors, confusion about what day it is or where you are, slurred speech, lethargy, and drowsiness. Some people develop a distinctive sign called asterixis, which is an involuntary flapping movement of the hands when the wrists are extended^[1][8].

In severe cases, people can experience extreme drowsiness, severe confusion or memory loss, disorientation in both time and place, and eventually loss of consciousness or coma^[1].

Often, family members or friends notice the first signs of hepatic encephalopathy before the person experiencing it does. The condition can sometimes be mistaken for dementia or depression^[5].

Grading system

Healthcare providers use a grading system called the West Haven Criteria to classify the severity of hepatic encephalopathy. It grades symptoms on a scale from 0 to 4^[1][11]:

Grade 0: Subtle changes in short-term memory, concentration, and reaction time that are only recognizable to you or those closest to you, or that might show up on specialized psychological tests. This stage is sometimes called minimal or covert hepatic encephalopathy.

Grade 1: Mild confusion or forgetfulness, mood swings like feeling unusually happy or anxious, difficulties with simple math like adding and subtracting, difficulties with fine motor skills like writing, and sleeping during the day while being awake at night.

Grade 2: Clear personality changes, inappropriate or out-of-character behaviors, lethargy and lack of interest, disorientation about what day or year it is, and slurred speech.

Grade 3: Slow thinking and sluggish movements, disorientation about where you are, drowsiness and loss of general awareness, severe confusion or memory loss, and involuntary twitching or tremors.

Grade 4: Total loss of consciousness, also called coma.

Stages 0 to 1 are sometimes called minimal hepatic encephalopathy because symptoms may not be outwardly noticeable. Stages 2 to 4 are called overt hepatic encephalopathy and feature more obvious symptoms^[1].

Common triggers

Even if you have liver disease, hepatic encephalopathy often develops or worsens because of a specific trigger. Recognizing and treating these triggers is an important part of managing the condition^[3][8].

The most common triggers include^[8][14]:

• Infections, especially spontaneous bacterial peritonitis (an infection of fluid in the abdomen), urinary tract infections, and pneumonia. Infections are the most frequent cause of hepatic encephalopathy episodes.
• Gastrointestinal bleeding, which increases the amount of protein-containing blood in your intestines that bacteria can break down into ammonia.
• Dehydration from excessive use of diuretics (water pills), overuse of laxatives, or large-volume fluid removal from the abdomen.
• Constipation or not taking prescribed medications like lactulose or rifaximin.
• Electrolyte imbalances, especially low sodium or potassium levels.
• Kidney problems, which prevent proper removal of toxins.
• Medications that affect the brain, especially opioids, sedatives, or sleeping pills.
• Eating too much protein at once.

Less common triggers include procedures that create connections between blood vessels (such as a TIPS procedure), alcohol use, and blood clots in veins^[2][17].

How it is diagnosed

Hepatic encephalopathy is considered a diagnosis of exclusion, which means doctors must rule out other possible causes of confusion or altered behavior before confirming this condition^[3].

Your doctor will start by looking at your medical history, current symptoms, and medication use. They will perform a physical examination and look for signs of liver disease and brain dysfunction^[11].

Several tests may be used to help diagnose hepatic encephalopathy and rule out other conditions^[11]:

Blood tests check for ammonia levels, electrolytes, glucose, markers of infection, and signs of kidney or liver problems. These tests also help identify whether alcohol, medications, or other conditions might be causing symptoms.

Psychological and neuropsychological tests assess thinking skills, memory, motor coordination, and reaction time. Tests might involve naming as many animals as you can think of in one minute, or tasks using pencil and paper to measure hand coordination and speed.

Imaging tests such as CT scans or MRI may be done to look at the liver, blood vessels, and brain. These help rule out stroke, bleeding in the brain, or other structural problems.

Electroencephalogram (EEG) measures electrical activity in the brain and can help healthcare professionals understand the severity of the condition.

Doctors will also check for infections by doing tests such as removing and testing abdominal fluid if present, chest X-rays, urine tests, and blood cultures. Finding and treating infections is critical because they are the most common trigger^[8].

Treatment approaches

Treatment of hepatic encephalopathy focuses on three main goals: identifying and treating triggers, lowering ammonia levels in the blood, and providing supportive care^[3][13].

Finding and treating triggers is the most important first step. This includes treating any infections with antibiotics, stopping gastrointestinal bleeding, correcting dehydration and electrolyte imbalances, and reviewing all medications to stop those that might be contributing to confusion^[8].

Lowering ammonia levels is typically done with medications. The two main treatments are^[15]:

Lactulose is a sweet-tasting liquid that works in several ways. When it reaches your colon, bacteria break it down into acids that trap ammonia in a form that cannot be absorbed. It also works as a laxative, causing frequent bowel movements that help remove ammonia from your body more quickly. Lactulose has been used since the 1960s and remains a cornerstone of treatment^[15].

Rifaximin is an antibiotic that stays in your intestines and changes the types of bacteria living there, reducing the bacteria that produce ammonia. It is often used together with lactulose^[15].

In severe cases, patients may need a procedure called polyethylene glycol preparation, similar to what is used before a colonoscopy, to rapidly clear the intestines^[14].

Supportive care includes providing proper nutrition, avoiding sedating medications that can worsen symptoms, and in some cases providing breathing support if consciousness is severely impaired^[14].

For people with recurrent episodes that do not respond to standard treatments, or for those with very advanced liver disease, liver transplantation may be the best long-term solution^[13].

What to expect

Hepatic encephalopathy can improve with treatment, but it can be life-threatening without proper care. Any symptoms of obvious hepatic encephalopathy are serious and require prompt medical attention to prevent the condition from worsening or causing permanent damage^[1].

If you see severe symptoms like extreme drowsiness, severe confusion or memory loss, disorientation about where you are or what day it is, or involuntary movements, treatment is especially urgent. Severe hepatic encephalopathy can advance to coma or death^[1].

The development of hepatic encephalopathy negatively affects survival. People who develop encephalopathy severe enough to require hospitalization have a survival probability of about 42% at one year and 23% at three years^[7].

However, with proper treatment and management of triggers, many people experience improvement. The key is recognizing symptoms early, seeking prompt medical care, taking prescribed medications as directed, and working closely with your healthcare team to identify and avoid triggers^[13].

Dietary changes are also important. Contrary to old beliefs, protein restriction is no longer recommended for people with hepatic encephalopathy. Instead, eating regular, balanced meals with adequate protein and calories throughout the day helps maintain nutritional status and may improve outcomes^[22].

Information for caregivers

Caring for someone with hepatic encephalopathy can be difficult and may feel like a full-time job. Caregivers often notice the first signs of the condition before the person experiencing it does, and they play a crucial role in recognizing when symptoms are worsening^[4][19].

As a caregiver, it is important to watch for changes in behavior, personality, sleep patterns, and ability to perform daily tasks. Keep track of symptoms and share this information with healthcare providers. Make sure medications are taken as prescribed, especially lactulose and rifaximin, as skipping doses can trigger episodes^[19].

Help monitor for signs of infection, dehydration, or gastrointestinal bleeding, and seek medical care promptly if these occur. Encourage regular, balanced meals and help ensure adequate nutrition^[19].

Caring for someone with hepatic encephalopathy is emotionally and physically demanding. It is essential to take care of yourself as well. Seek support from family, friends, healthcare providers, or support groups. Taking breaks and asking for help when needed will help you provide better care over the long term^[19].