Hepatic Encephalopathy

What is Hepatic Encephalopathy?

Hepatic encephalopathy is a condition that might be reversed and usually affects people suffering from advanced liver problems. This condition causes various mental or psychological issues due to the buildup of harmful substances in the blood. Often, this disorder associates with preexisting liver diseases such as cirrhosis, but can also affect individuals without previous liver problems. For these individuals, severe liver failure can cause their brain to swell, leading to a coma in extreme cases. Hepatic encephalopathy in patients with ongoing liver disease might be managed and possibly reversed. However, in sudden or aggressive cases, controlling it can be hard due to widespread brain swelling and injuries to the brainstem structure.

Hepatic encephalopathy symptoms can occur from liver insufficiency or when blood flow is redirected away from the liver. According to the International Society for Hepatic Encephalopathy and Nitrogen Metabolism, the onset of overt hepatic encephalopathy is characterized by instances of disorientation or uncontrolled flapping movements of the hand (known as asterixis). Detecting the onset in patients with advanced liver disease can be tough. Some patients may show minor signs that can only be spotted through specialized tests. This condition is known as minimal hepatic encephalopathy and is present in almost 80% of patients with cirrhosis.

Hepatic encephalopathy can cause symptoms such as confusion, personality changes, disorientation, and reduced awareness. In early stages, patients often have a disrupted sleep pattern, tending to sleep during the day and staying awake at night. As the condition worsens, patients typically experience increasing confusion, lethargy, and personality changes. In advanced stages, hepatic encephalopathy can lead to a coma, a condition known as hepatic coma, which can be deadly. In severe cases among patients with acute liver failure or known cirrhosis, more than 50% die within the first year.

What Causes Hepatic Encephalopathy?

Hepatic encephalopathy, a condition that causes confusion and poor brain function, can occur due to underlying liver disease or issues with certain blood vessels. This condition could happen because of liver infections or due to what is known as a “shunt” – a passageway that redirects blood flow around the liver directly into the body’s general blood circulation. In the latter case, the liver gets bypassed, and harmful substances build up in the body.

Some conditions that can cause sudden liver failure include viral infections affecting the liver, exposure to harmful substances or toxins such as certain mushrooms, substances like acetaminophen, and excessive alcohol consumption. This can also include ischemic liver injury, which is damage to the liver caused by a lack of blood supply, often due to conditions like severe infection or shock. On the other hand, chronic (long-term) liver failure and scarring (cirrhosis) can result from conditions such as long-lasting alcohol abuse, chronic infections with hepatitis B or C, a condition called non-alcoholic fatty liver disease (build-up of fat in the liver), and certain genetic conditions.

For people who are already suffering from liver cirrhosis, hepatic encephalopathy can be caused by a variety of factors. These may include kidney failure, gastrointestinal bleeding (like from swollen blood vessels in the esophagus), constipation, infections, not taking prescribed medications properly, unduly high protein intake, dehydration due to multiple causes (like vomiting, diarrhea, fluid restrictions, water pills, or excessive fluid removal from the abdomen), imbalances in body salts or minerals, alcohol consumption, and use of particular types of painkillers or sedatives.

Having a bypass surgery of the liver blood vessels, or TIPS, can lead to hepatic encephalopathy in about 30% to 50% of individuals with liver cirrhosis. Another trigger can be spontaneous portosystemic shunts – these are natural bypass routes that can open due to liver scarring, directing blood away from the liver and into the general circulation. This can contribute to hepatic encephalopathy and make liver failure worse over time.

Risk Factors and Frequency for Hepatic Encephalopathy

Hepatic encephalopathy is a common complication in those with cirrhosis, with one study suggesting around 44% of cirrhosis patients experiencing it within a 5-year period. Another study found nearly one-third of cirrhosis patients had an advanced stage of the disease, and half of those experienced hepatic encephalopathy.

Chronic liver disease often has a slow, subtle onset, which can unfortunately lead to delays in treatment. This can result in complications like hepatic encephalopathy, and in 2018 alone, an estimated 202,000 cases of it were reported in the United States. However, it’s important to remember that some forms of hepatic encephalopathy are very mild and aren’t easy to detect without special tests. As many as 80% of cirrhosis patients may be affected by these minimal forms of hepatic encephalopathy.

• Approximately 44% of cirrhosis patients develop hepatic encephalopathy within 5 years, according to one study.
• Another study of over 9,000 patients newly diagnosed with cirrhosis found that around one-third had an advanced stage of the disease, and of those, 51% experienced hepatic encephalopathy.
• Chronic liver disease often starts subtly and gradually, which can lead to delayed treatment and complications like hepatic encephalopathy.
• In 2018, around 202,000 cases of hepatic encephalopathy were reported in the US.
• However, these figures might not include mild forms of hepatic encephalopathy, which can affect up to 80% of cirrhosis patients and are not easily detectable without specialized tests.

Signs and Symptoms of Hepatic Encephalopathy

Hepatic encephalopathy is a condition that affects brain function due to liver disease. Diagnosing it involves confirming liver disease through a variety of methods, such as abnormal liver function tests, imaging, or a liver biopsy. Another aspect could be identifying the presence of a “portosystemic shunt”. It’s also crucial to make sure no other conditions are causing similar symptoms – this could include brain lesions, masses, strokes, seizures, and certain infections, among other things.

Getting the patient’s medical history is also very helpful – it can provide important clues about what could be causing liver failure. If the patient is unable to communicate, doctors may talk with family members or friends to gather information. When collecting a patient’s history, doctors consider:

• Symptoms associated with liver failure and complications this might cause, like jaundice, itching, belly bleeding, blood clotting abnormalities, increased belly size, kidney failure, and changes in mental state
• Changes in sleep habits and thinking abilities, which could mean decreased attention span and problems with short-term memory. These issues could, in turn, affect day-to-day activities.
• History of exposure to substances that can hurt the liver, such as alcohol, medications, and some types of herbal medicine. Other dangerous substances could also include certain mushrooms, solvents, or items that contain phosphorus, like fireworks.
• Things that could increase the risk of viral hepatitis, such as travel history, blood transfusions, sexual behavior, or specific occupations
• Family history of liver disease, for example, conditions like Wilson disease or alpha-1 antitrypsin deficiency
• An underlying cause for encephalopathy, such as constipation, infection, use of sedatives, episodes of gastrointestinal bleeding, or conditions leading to dehydration, like diarrhea or vomiting.

During a physical examination, doctors typically see signs of advanced chronic liver disease (often called “decompensated cirrhosis”) in patients with hepatic encephalopathy. Some of these physical signs include:

• Muscle wasting
• Jaundice
• Ascites (fluid build-up in the belly)
• Reddening of the palms
• Swelling
• Spider-like spots on skin
• A distinctive odor from breath known as fetor hepaticus

However, in patients with sudden severe hepatitis who don’t have a history of chronic liver disease, some of these signs could be missing as they need more prolonged liver dysfunction to occur. These patients often show decreased muscle mass, strength, and function, known as sarcopenia, which is closely linked to an increased risk of hepatic encephalopathy.

Patients with hepatic encephalopathy also tend to have changes in cognitive function and muscle performance. Early signs involve reduced awareness of the environment and may include yawning or dozing off episodes. Sleep disturbances – sleeping too much or too little – are common and can appear before other mental or muscular symptoms. Muscle-related symptoms of hepatic encephalopathy range from slow movement, ‘flapping’ of hands when outstretched, slurred speech and lack of coordination, to hyperactive tendon reflexes, and nystagmus (quick, uncontrolled eye movements). Some individuals may display symptoms that resemble Parkinson’s disease, such as stiffness and shaking. In severe cases, reflexes may be lost, and patients can become comatose. Some patients may show focal neurological deficits despite negative findings on brain CT scans or MRIs.

Testing for Hepatic Encephalopathy

If your doctor suspects you have hepatic encephalopathy (a decline in brain function that can occur due to severe liver disease), they will start by assessing crucial signs like your heartbeat, temperature, and your breathing. It’s also important to distinguish between certain physical signs such as asterixis (a flapping tremor of the hand) and uncontrollable shaking that can sometimes be mistaken for conditions related to alcohol withdrawal.

The first test that doctors typically carry out measures ammonia levels in your blood. While ammonia is a substance that can harm your brain, having high ammonia levels in your blood isn’t always necessary for a diagnosis of hepatic encephalopathy. In fact, understanding how your condition changes during treatment is more helpful than relying only on repeating this specific blood test.

Doctors will also perform liver function tests and assess the levels of different elements in your blood. As hepatic encephalopathy is linked to liver disease, the results of these tests can often be abnormal. For example, you might have high levels of bilirubin and certain enzymes (like aspartate aminotransferase and alanine aminotransferase), or it might take longer for your blood to clot (indicated by a longer prothrombin time and higher INR value). Additionally, due to liver dysfunction or the use of certain types of medication (diuretics), you may also have imbalances in your blood sodium and potassium levels.

Another type of test detects the levels of a certain substance, 3-nitrotyrosine, in your blood. Some studies suggested that elevated levels of this substance are common in patients with mild hepatic encephalopathy, and that it can help identify the condition with a fairly high level of accuracy.

The doctor may also carry out psychological tests that assess your mental function. Though these tests are more sensitive than the common brain wave test (EEG) for identifying minor mental function problems, they can be complex and time-consuming, so aren’t used as standard clinical tools.

One widely used test, the Number Connection Test (NCT), is simple to carry out and easy to interpret. This test requires the patient to connect numbers in sequence within a time limit related to their age.

An electroencephalogram (EEG) captures brain wave activity, providing insight into possible changes that could indicate hepatic encephalopathy. However, these findings are not exclusive to this condition. An EEG is useful to rule out other conditions like seizure disorders.

Imaging tests like CT or MRI can be used to help rule out other possible causes of your symptoms, such as brain lesions, tumors, or bleeding. While MRI is better at identifying brain swelling in liver failure, it is not a standard test for diagnosing hepatic encephalopathy. Some MRI images may show an enhanced signal in the basal ganglia (a region of the brain) in patients with hepatic encephalopathy, potentially because of a build-up of the metal manganese. However, it’s important to note that these changes are not always present and are not specific to hepatic encephalopathy.

Treatment Options for Hepatic Encephalopathy

The treatment of hepatic encephalopathy, a condition affecting brain function due to liver disease, usually combines supportive care with therapy to reduce levels of ammonia, a harmful substance often found in high amounts in patients. Key parts of supportive care include maintaining good nutrition, preventing dehydration and electrolyte imbalance, and ensuring patient safety.

Nutrition is important. Rather than limiting protein, patients should receive sufficient calories, with protein making up an appropriate part of the diet. Small meals throughout the day are encouraged to discourage fasting and thereby stop elevated ammonia production. For patients who have difficulty tolerating protein, options like plant-based protein or branched-chain amino acids, a type of amino acid, may be considered. This approach is especially good for patients who have certain procedures and experience hepatic encephalopathy.

Also, it is important to make sure patients stay hydrated and have proper amounts of electrolytes in their bodies. This may involve drinking enough fluids and, in some cases, receiving intravenous fluids to prevent dehydration. Any electrolyte imbalances should be corrected by providing necessary electrolytes.

Patients with clear symptoms need a safe environment as they might be restless and could be a danger to themselves or their caregivers. While addressing restlessness, we need to be aware that sedatives may make the encephalopathy worse and slow recovery. So, their use needs to be cautious in some cases.

Identifying and treating any triggers for hepatic encephalopathy are vital. This could be constipation, infections, electrolyte and metabolic imbalances, dehydration, or use of sedatives, among other factors. Prompt action to correct these triggers is key to effective treatment.

In most hepatic encephalopathy cases, high levels of ammonia are found but that’s not always the case. Whether the ammonia levels are high or not, once hepatic encephalopathy is diagnosed, steps to reduce ammonia should be taken. However, it’s important to remember that the decision to start therapy to reduce ammonia should be based on the patient’s symptoms, not just their blood ammonia levels.

Common medications used to manage the condition include disaccharides like lactulose and lactitol, and the antibiotic rifaximin.

Lactulose works through a variety of ways. It reduces the amount of ammonia in the blood by causing the ammonia to turn into ammonium, a form that doesn’t easily enter the bloodstream. Lactulose also increases the rate of ammonia moving from the blood into the gut, where it’s turned into ammonium. Lastly, it promotes bowel movement, which helps get rid of ammonia. Typically, it is given in a dosage that achieves 2 to 3 soft stools daily. In cases where it can’t be taken orally, it can also be given as an enema. Around 70% to 80% of patients with hepatic encephalopathy show improvement with lactulose treatment.

Rifaximin is an antibiotic that reduces ammonia production by eliminating ammonia-producing bacteria in the colon. It binds to a bacterial enzyme, inhibits bacterial RNA synthesis and can be considered for patients who don’t respond to lactulose or lactitol or have intolerance to these medications.

Neomycin, another antibiotic, was previously explored to reduce ammonia-producing bacteria in the colon. However, studies have shown inconsistent results with neomycin and it carries the risk of side effects. Therefore, neomycin is not commonly used due to limited effectiveness and potential side effects.

For individuals at risk of recurrent hepatic encephalopathy, it is crucial to identify and manage potential triggers. If a trigger cannot be controlled effectively, patients may benefit from ongoing therapy with disaccharides like lactulose or lactitol in combination with rifaximin.

In patients with cirrhosis, a condition that causes scarring of the liver, liver transplantation is usually considered when there are major complications or when the disease has progressed significantly. Importantly, cognitive impairment associated with hepatic encephalopathy appears to be reversible within 5 years following the transplantation procedure. This suggests that successful liver transplantation can significantly improve cognitive function and quality of life.

What else can Hepatic Encephalopathy be?

If a person is showing symptoms of hepatic encephalopathy, the physician will consider several potential diagnoses. The possible conditions that might be causing the symptoms can be grouped into several categories:

• Conditions related to the brain: these could include a subdural hematoma, intracranial hemorrhage, tumor, stroke, or abscess
• Other processes occurring within the central nervous system: these could include meningitis, Wernicke encephalopathy, or post-seizure encephalopathy
• Metabolic causes: these could include low blood sugar (hypoglycemia), a lack of oxygen (anoxia), intoxication from alcohol, or withdrawal from alcohol
• Effects related to drugs: these could include antipsychotics, sedatives, or antidepressants

This isn’t an exhaustive list, but it provides an idea of the diverse range of conditions that might initially present with similar symptoms to hepatic encephalopathy. It’s important for the physician to carefully review these alternatives and carry out appropriate medical tests to determine what’s causing the patient’s symptoms.

What to expect with Hepatic Encephalopathy

People with chronic liver disease who have experienced a condition known as hepatic encephalopathy (a decline in brain function as a result of severe liver disease) are often at risk of it recurring. Even after receiving treatment, these individuals may still have ongoing neurological problems despite seeming mentally normal.

The severity of these ongoing problems tends to be higher in individuals who have had multiple severe instances of hepatic encephalopathy. This condition is also very serious and often indicates a poor outlook for those with liver failure.

Research involving patients with hepatic encephalopathy who were admitted to the hospital showed that slightly less than half (44%) were still living at 12 months, and about a third (35%) were still living after two years.

Possible Complications When Diagnosed with Hepatic Encephalopathy

Hepatic encephalopathy, a condition that affects the brain and is tied to liver disease, can cause various complications. Some people might become agitated, potentially posing a danger to themselves or others who are helping them. Seizures are another issue that could rise. Even with clinical improvements, some people may continue to experience problems in their cognitive function.

Another serious aspect is that individuals with recurrent episodes of this condition could see their chances of survival drop within a 12 to 24 month period. Patients experiencing an acute and severe form of liver failure might also face brain swelling, seizures, and a shift in brain tissue known as brain herniation.

Complications:

• Agitation, posing a potential risk to the patient and caregivers
• Seizures
• Residual cognitive impairment, even after clinical improvement
• Decreased survival rates for those with recurrent episodes within 12 to 24 months
• Brain swelling, seizures, and brain tissue shift in acute severe liver failure

Recovery from Hepatic Encephalopathy

A research study found that 7.2% of patients with a liver disease called cirrhosis developed a condition called hepatic encephalopathy after undergoing surgery not related to the liver. Hepatic encephalopathy is a deterioration in brain function that occurs as a result of severe liver disease. It can have negative effects post-surgery.

Therefore, it’s very important to improve the patient’s pre-surgery condition using a score referred to as the Child-Turcotte-Pugh (CTP) score, which measures the severity of cirrhosis. It’s also important to address any problems with fluid dynamics in the body (hemodynamic) and metabolism before considering elective (non-emergency) surgery. This helps reduce the risk of developing hepatic encephalopathy after the surgery. Using anesthetics that are less damaging to the liver can also contribute to better results.

After surgery and during the recovery period, it’s crucial to keep a close eye on any abnormalities in electrolyte levels. Electrolytes are minerals in the body that have an electric charge, like potassium and sodium, which are vital for heart and nerve function.

Preventing constipation and infections is also important. Special attention should be given to nutrition. Making sure patients get enough calories is important, and limiting protein should be avoided. It is crucial to avoid medications that could damage the kidneys (nephrotoxic) or the liver (hepatotoxic). Sedatives, which are drugs that calm or soothe, should be used very cautiously.

Preventing Hepatic Encephalopathy

Patients who are at risk of developing a condition known as hepatic encephalopathy, which affects brain function due to liver disease, need to be well-educated about this condition. They should understand the various aspects such as its symptoms, what can trigger its onset, how to manage it long-term, and when to seek help. Both these patients and their families should be well-informed and stay alert.

Here are some important points that patients and their families need to keep in mind:

* It’s crucial to spot the early warning signs of hepatic encephalopathy. These signs could include changes in your sleep patterns, becoming easily confused, or having a shortened attention span.

It’s also important to be aware of what can potentially trigger hepatic encephalopathy. This can include things like infections, constipation, medications that make you sleepy, bleeding in your digestive tract, and not drinking enough fluids.

You should also make sure to avoid things that can harm your liver, such as alcohol and certain herbal medications. It’s essential to take your prescribed medications as your doctor instructs. For example, if you’ve been prescribed a medication named lactulose, it’s important that you have at least 2 to 3 bowel movements per day. If you’re on a medication called rifaximin, you should stick to your treatment plan. This is because these medications work best when taken correctly.

Lastly, it’s important to seek immediate medical help if symptoms worsen. Examples of troubling symptoms can include fever, increased belly swelling, increased yellowing of the skin and eyes (known as jaundice), difficulty staying awake or noticeable changes in mental status.