Acute Hepatic Failure

Acute hepatic failure is a rare but life-threatening condition where the liver rapidly loses its ability to function within days or weeks, leading to serious complications that can affect the entire body.

Table of contents

• What is Acute Hepatic Failure?
• Common Causes
• Signs and Symptoms
• How It Is Diagnosed
• Serious Complications
• Treatment Options
• Outlook and Survival

What is Acute Hepatic Failure?

Acute hepatic failure, also called acute liver failure, is a medical emergency where the liver suddenly stops working properly in someone who previously had a healthy liver. This condition develops rapidly, usually within days or weeks, rather than over months or years like chronic liver disease^[1].

The liver is one of your essential organs that performs hundreds of vital functions in your body. When it fails suddenly, your body can no longer remove toxins from the blood, make proteins that help blood clot, or process nutrients from food properly^[5]. This rapid loss of function distinguishes acute hepatic failure from chronic liver failure, which develops slowly over time.

The condition is defined by the presence of problems with blood clotting (with an international normalized ratio, or INR, greater than 1.5) and mental confusion or changes (called encephalopathy) that develop within 26 weeks of the first signs of liver problems in someone without previous liver disease^[2].

Doctors classify acute hepatic failure into different types based on how quickly symptoms develop. Hyperacute failure occurs within 7 days, acute failure develops within 1 to 4 weeks, and subacute failure takes more than 4 weeks to develop^[2]. The speed at which the disease progresses affects both treatment options and chances of recovery.

Common Causes

The causes of acute hepatic failure vary depending on where you live. In the United States, taking too much acetaminophen (found in medications like Tylenol) is the most common cause, followed by viral hepatitis^[4]. Acetaminophen poisoning can happen when people accidentally take too much by using multiple medicines containing this ingredient at the same time, or when the regular dose doesn’t seem to work and more is taken^[11].

Other important causes include:

• Viral hepatitis: Infections with hepatitis viruses, particularly hepatitis A, B, and E, can sometimes cause sudden liver failure^[1].
• Medications and drugs: Various prescription medicines including antibiotics, anti-inflammatory drugs, and anticonvulsants can trigger acute liver failure^[11].
• Herbal supplements: Common herbs such as aloe vera, chaparral, comfrey, ephedra, and kava can be toxic to the liver^[11].
• Poisonous mushrooms: Eating certain types of poisonous mushrooms can cause rapid liver damage^[11].
• Wilson’s disease: This rare inherited condition causes copper to build up in the liver^[2].
• Autoimmune hepatitis: The body’s immune system mistakenly attacks the liver^[2].
• Blood vessel problems: Conditions like Budd-Chiari syndrome block blood flow in liver veins^[11].
• Cancer: Cancer that starts in or spreads to the liver can cause acute liver failure^[11].
• Hepatic ischemia: When blood flow to the liver is severely reduced, liver cells can die quickly^[4].

In some cases, doctors cannot identify the exact cause despite thorough investigation^[4].

Signs and Symptoms

The symptoms of acute hepatic failure can develop quickly and affect many parts of the body. Early symptoms often include general feelings of illness that may not immediately point to liver problems^[4].

Common early symptoms include:

• Extreme tiredness and feeling generally unwell^[1]
• Nausea and vomiting^[1]
• Loss of appetite^[5]
• Pain in the upper right part of the abdomen^[1]

As the condition progresses, more specific signs of liver failure appear:

• Jaundice: Yellowing of the skin and the white parts of the eyes, caused by the buildup of a substance called bilirubin^[1]
• Swelling of the abdomen due to fluid buildup (called ascites)^[1]
• Mental confusion, disorientation, or changes in behavior^[1]
• Extreme sleepiness or difficulty staying awake^[1]
• Trembling or shaking, especially of the hands^[1]
• Breath that smells musty or sweet^[1]
• Easy bruising or bleeding problems^[5]

Because acute hepatic failure can develop so rapidly, it is critical to seek medical attention immediately if you or someone you know suddenly develops yellowing of the eyes or skin, pain in the upper abdomen, or unusual changes in mental state or behavior^[1].

The condition can affect multiple organ systems as it progresses. Symptoms typically start with a period of fatigue, nausea, vomiting, right upper abdominal pain, and jaundice, followed by problems in multiple organs throughout the body^[4].

How It Is Diagnosed

Diagnosing acute hepatic failure requires several tests and examinations. The most important step is to identify the cause quickly, because certain conditions need immediate and specific treatment^[6].

All patients with signs of moderate or severe sudden liver problems should have immediate measurement of how long it takes their blood to clot (called prothrombin time) and careful evaluation of their mental status. If blood clotting is abnormal or mental state changes are present, hospital admission is necessary^[6].

Blood tests are essential for diagnosis and include:

• Tests to measure how long blood takes to clot (prothrombin time or INR)^[9]
• Liver function tests that measure levels of enzymes and other substances produced by the liver^[6]
• Blood counts to check for low platelets^[6]
• Tests to measure ammonia levels, which often become very high^[6]
• Blood sugar levels, which may become dangerously low^[6]
• Tests to identify specific causes like hepatitis viruses, drug levels, or Wilson’s disease^[4]

Imaging tests help doctors see the liver and identify possible causes:

• Ultrasound examination uses sound waves to create pictures of the liver and can show liver damage^[9]
• CT scans (computerized tomography) provide detailed images of the liver and blood vessels^[9]
• MRI (magnetic resonance imaging) can look for specific causes like blood vessel blockages or tumors^[9]

In some cases, a liver biopsy may be needed to help determine why the liver is failing. This involves removing a small piece of liver tissue for examination under a microscope. Because people with acute hepatic failure have problems with bleeding, a special type of biopsy called a transjugular liver biopsy may be performed through a vein in the neck rather than directly through the abdomen^[9].

Doctors also gather important information from the patient’s history, including all medications (including over-the-counter drugs and herbal supplements), possible exposure to hepatitis viruses, history of autoimmune diseases, substance use, and any previous liver problems^[4].

The pattern of liver enzyme abnormalities can provide clues about the cause. Very high levels of certain enzymes (≥3000 IU/L) may suggest viral hepatitis, acetaminophen overdose, or reduced blood flow to the liver^[4].

Serious Complications

Acute hepatic failure can lead to several life-threatening complications that affect different parts of the body.

Brain swelling (cerebral edema) is the most dangerous complication and the major cause of death in patients with acute hepatic failure. When the liver fails, toxic substances like ammonia build up in the blood and reach the brain. This causes brain cells to swell, increasing pressure inside the skull^[4]. Brain swelling is seen in about 80% of patients with the most severe level of mental confusion and can lead to brain herniation and death^[4]. The faster the liver failure develops, the higher the risk of brain swelling^[2].

Bleeding problems (coagulopathy) occur because the liver normally produces most of the proteins needed for blood clotting. When it fails, patients can develop dangerous bleeding^[8].

Kidney failure is another common complication. The kidneys may stop working properly as the liver failure progresses^[8].

Infections are common because the immune system doesn’t work as well when the liver fails. Patients become more susceptible to bacterial and fungal infections^[8].

Low blood sugar (hypoglycemia) can occur because the liver normally helps maintain blood sugar levels. When it fails, blood sugar can drop to dangerous levels^[6].

Blood pressure and breathing problems may develop as the condition affects the heart and lungs. Blood pressure may drop too low, and patients may have difficulty getting enough oxygen^[8].

These complications require intensive medical care and close monitoring in a hospital intensive care unit^[9].

Treatment Options

People with acute hepatic failure need treatment in an intensive care unit, ideally at a medical center that can perform liver transplants if necessary^[9]. The treatment focuses on supporting the body’s functions while the liver tries to recover, preventing complications, and treating the underlying cause when possible.

Specific treatments for the cause:

For acetaminophen overdose, a medication called N-acetylcysteine can help stop further liver damage if given early enough^[14]. For certain types of poisoning, such as from mushrooms, specific treatments may be available. For viral hepatitis or autoimmune hepatitis, specific medications may be used^[9].

Managing brain swelling:

Preventing and treating brain swelling is critical. Patients are positioned with their head elevated. Medications may be given to reduce brain swelling. In severe cases, machines may be used to help patients breathe, and medications to reduce ammonia levels may be administered^[14].

Preventing infections:

Because patients with acute hepatic failure are at high risk for infections, doctors carefully monitor for signs of infection and may give antibiotics or antifungal medications^[14].

Managing bleeding:

Medications to protect the stomach lining (such as proton pump inhibitors) are given to all patients to prevent bleeding in the digestive tract. If serious bleeding occurs, blood products may be given^[14].

Nutritional support:

Patients need careful management of their nutrition and blood sugar levels. Feeding through a tube may be necessary if patients cannot eat^[14].

Fluid and blood pressure management:

Careful monitoring and adjustment of fluids and medications are needed to maintain proper blood pressure and organ function^[14].

Liver transplantation:

For many patients with severe acute hepatic failure, a liver transplant is the only cure^[1]. When the liver is too damaged to recover on its own, replacing it with a healthy donor liver can be life-saving. Liver transplant is considered the cornerstone of therapy for patients not responding to other treatments^[16]. In Western countries, liver transplantation has become the standard of care for most patients with this condition^[21].

The decision about whether someone needs a liver transplant is made by a team of specialists who consider many factors, including the cause of liver failure, how quickly the condition is progressing, and whether complications are developing^[4].

Outlook and Survival

The outlook for patients with acute hepatic failure depends on several factors, including the cause of the liver failure, how quickly it develops, and whether a liver transplant is available.

Overall survival rates have improved significantly over the past few decades. Survival increased from about 20% to greater than 60% due to improvements in intensive care and the availability of liver transplantation^[4]. However, without treatment, the mortality rate remains high, and transplant-free survival for all patients is only about 50% according to large studies^[4].

The speed of disease development affects prognosis. Patients with hyperacute liver failure (developing within 7 days) generally have a better chance of recovery with medical management alone, despite having a higher risk of brain swelling. In contrast, those with subacute liver failure (developing over 5 to 26 weeks) have a poorer prognosis without liver transplant, though they have a lower risk of brain swelling^[16].

The cause of liver failure also influences survival. Some causes respond better to medical treatment than others^[4].

For patients who receive a liver transplant, outcomes are generally good. One-year survival rates after transplant exceed 80% in many medical centers^[2].

The time between the first appearance of jaundice and the development of mental confusion is an important indicator of prognosis^[2]. Early recognition of the condition and transfer to a specialized medical center with transplant facilities is critical for improving survival^[16].

For patients who survive, whether through recovery or transplantation, the outlook is generally good, as this is an acute condition and survivors typically recover completely without lasting effects^[21].

• Liver

fulminant hepatic failure, acute liver failure