What is Acute Liver Failure (Liver Failure)?

Acute liver failure (ALF) is a serious and sometimes complex condition that results in severe dysfunction of the liver in patients without any prior liver disease. Despite its high risk of sickness and death, strides have been made in medical care and emergency liver transplants to improve survival rates. It’s very important to be aware of this condition, refer patients to a liver transplant specialist early, and ensure they receive the proper supportive care.

Looking forward, it’s hoped that a more thorough understanding of how liver damage occurs and how to manage failures of multiple organs will help improve patient outcomes. ALF is characterized by a sudden, severe injury to the liver that is accompanied by encephalopathy, a condition that affects the brain. Patients also show signs of impaired liver function (measured by an INR of 1.5 or higher). All of this occurs in patients without any prior liver disease, and within 26 weeks or less of falling ill.

What Causes Acute Liver Failure (Liver Failure)?

Determining the cause of Acute Liver Failure (ALF) is very important, as it helps doctors create a treatment plan and predict the outcome. Most commonly, ALF is caused by viral hepatitis and drug-induced hepatitis worldwide. It can also be triggered by factors such as oxygen shortage-induced liver injury, unique blood vessel disorders in the liver, a rare genetic disorder called Wilson disease, eating poisonous mushrooms, widespread infection, autoimmune liver disease, a liver condition during pregnancy, liver complications from a dangerous pregnancy condition, heatstroke, or cancer spreading to the liver.

In the United States, drug-related hepatitis, specifically caused by the overuse of the drug acetaminophen, is responsible for almost half of ALF cases. The harm this drug can do to the liver largely depends on the amount taken. While it is rare, some people might have a unique negative reaction to a drug that can lead to liver damage. Moreover, unintentional usage of medication that damages the liver, like acetaminophen, is more often seen in individuals who abuse alcohol and are malnourished.

In developing countries, the leading culprits of liver failure are Hepatitis A and E. Hepatitis B can be the reason for liver failure due to both fresh infections and due to the reactivation of previous Hepatitis B after the start of treatments that suppress the immune system. Having both Hepatitis B and C infections simultaneously could also cause ALF, but this is rarely seen with Hepatitis C alone. Other viral causes of ALF include herpes simplex virus, cytomegalovirus, Epstein-Barr virus, Parvoviruses, adenovirus, and varicella-zoster virus.

Risk Factors and Frequency for Acute Liver Failure (Liver Failure)

The causes and occurrence rates of Acute Liver Failure (ALF) vary between developed and developing countries. In developing countries, Hepatitis A, B, and E are primarily responsible for ALF, while drug-induced liver injuries are more common in developed nations. Recent studies show that over the past 50 years, ALF due to Hepatitis A and B has decreased, whereas ALF resulting from acetaminophen, a common drug, has increased, particularly in the United States and Western Europe.

  • Hepatitis A, B, and E are the main causes of ALF in developing countries.
  • Drug-induced liver injury is the main cause of ALF in developed countries.
  • Over the past 50 years, occurrences of ALF from Hepatitis A and B have decreased.
  • The number of ALF cases due to acetaminophen has increased, especially in the United States and Western Europe.

Signs and Symptoms of Acute Liver Failure (Liver Failure)

A complete background check can help identify possible causes of liver disease. This can look at the patient’s medical history, their own account, or information from family members. Important details might include:

  • Previous instances of liver disease or liver decompensation (worsening liver function)
  • Any other chronic health conditions the patient has
  • The sequence and duration of the patient’s symptoms – this is particularly important in cases of over-the-counter drug overdose.
  • Potentially harmful habits or risky behaviours
  • Any medications taken recently, or exposure to substances that can damage the liver, including herbal products
  • Family history – especially for conditions like Wilson disease and blood clotting disorders.
  • Any recent surgeries where anesthetics might be the cause of the acute liver failure.

Signs of liver disease as found by a physical exam could include low blood pressure, changes in mental status, fever (if the cause is an infection), discomfort or pain in the upper right part of the stomach, symptoms of jaundice (yellowing skin or eyes), and signs of fluid buildup in the body like swelling.

Testing for Acute Liver Failure (Liver Failure)

If your doctor suspects liver damage, they may run several tests. They could check how long it takes your blood to clot, indicated by an INR value of 1.5 or higher. They might also measure your bilirubin and aminotransferases levels to detect liver function abnormalities and check for low platelet and red blood cell counts, low blood sugar, high ammonia levels, and signs of kidney damage. An imbalance of electrolytes in your blood (like low potassium or phosphate) is also common in these cases.

Getting images of different parts of your body would provide vital information too. With pictures of your abdomen, doctors can see if you have conditions like cirrhosis, portal hypertension, liver cancer, blood clots, swollen lymph nodes, or an enlarged spleen. An abdominal ultrasound could provide additional details, especially if there’s possibility of kidney damage or vascular thrombosis.

An MRI or CT scan of your brain can help doctors figure out if physical changes in your brain are causing mental status changes. Similarly, imaging of your chest can help rule out conditions such as fluid overload in your lungs or pneumonia. These details are crucial in determining the best course of treatment.

Treatment Options for Acute Liver Failure (Liver Failure)

Acute liver failure (ALF), a potentially life-threatening condition, requires a comprehensive approach to manage. This includes supportive care, managing complications, treating the underlying cause, and potentially considering a liver transplant. It’s best to treat patients in a hospital with facilities and doctors who specialize in liver transplants.

Supportive and Preventive Care

Patients need careful monitoring to maintain blood flow and fluid balance, while also checking acid-base levels and electrolytes. Any signs of bleeding need monitoring as these patients are at a high risk due to poor blood clotting and platelet function. In cases of active bleeding or before an invasive procedure, transfusion of blood products might be needed. If a patient gets a fever, blood and urine tests should be done and antibiotics started when necessary.

Patients might show signs of a worsening brain disorder caused by liver damage (hepatic encephalopathy). This could cause problems with swallowing and breathing, increasing the risk of inhaling food, stomach acid, or saliva into the lungs (aspiration). If these signs occur, the airway should be maintained by inserting a tube (intubation) and steps taken to avoid brain swelling (cerebral edema). Nutrition is vital with a target of 1.0 to 1.5 g of protein per kilogram of body weight per day. Low blood sugar (hypoglycemia) should also be monitored and treated.

Specific Treatment Based on the Cause

For patients where acetaminophen caused ALF, activated charcoal (if presented within 4 hours of ingestion) and N-acetyl cysteine (NAC) should be quickly administered. For patients with acute or ongoing hepatitis B, nucleotide analogues should be given. If autoimmune hepatitis is suspected, intravenous methylprednisolone may be useful. In patients suspected of mushroom poisoning, gastric lavage, activated charcoal, and intravenous penicillin G can be given.

If liver failure stems from Wilson’s disease or hepatic vein blockage, a liver transplant should be considered.

Patients with liver failure caused by herpes or varicella zoster infection should receive acyclovir. Those with Cytomegalovirus-induced liver failure should be given intravenous ganciclovir. In pregnant patients where acute fatty liver of pregnancy or HELLP syndrome might have caused the ALF, prompt delivery of the fetus is recommended.

Managing Complications

Every effort should be made to prevent multiple organ dysfunction. Complications such as kidney failure may occur and vasopressor therapy with norepinephrine or dopamine might be required to address severe low blood pressure. Dialysis might be considered to help manage the condition pending a potential liver transplant. Infections, including pneumonia, should be treated with broad-spectrum antibiotics.

Metabolic disorders like hypoglycemia and hypophosphatemia need management with continuous glucose infusions and aggressive phosphorus supplementation. Seizure-like activity can be treated with phenytoin or benzodiazepines.

Cerebral edema is a major concern and the most common cause of death in ALF. Steps should be taken to keep the intracranial pressure below 25 mm Hg. Coagulopathy or abnormal blood clotting is also a defining feature of ALF. While bleeding events are rare, routine correction of coagulopathy is not recommended unless there is overt bleeding or before invasive procedures.

Liver Support and Transplantation

Liver transplantation is an option for selected patients, but it’s not readily available and comes with an increased risk of graft complications. Extracorporeal liver-assist devices have seen some use in clinical trials but recent studies showed no survival benefit. Transplant patients are critically ill and are at greater risk of complications, most commonly from infections and sepsis.

  • Sudden onset fatty liver during pregnancy
  • Poisoning from Amanita phalloidesmushroom
  • Toxins from the Bacillus cereus bacteria
  • Inability to digest fructose (Fructose intolerance)
  • Metabolic disorder affecting the ability to process galactose (Galactosemia)
  • A severe pregnancy complication caused by problems with blood cells called HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome
  • Infections from hemorrhagic viruses such as Ebola, Lassa, and Marburg
  • Unexplained allergic reaction to drugs (Idiopathic drug hypersensitivity)
  • A newborn disease related to excess iron storage (Neonatal iron storage disease)
  • Disorder of the metabolism of the amino acid tyrosine (Tyrosinemia)

What to expect with Acute Liver Failure (Liver Failure)

The outcomes for Acute Liver Failure (ALF) patients have significantly improved over the past 50 years. Nowadays, it’s estimated that over 65% of patients, including those who receive liver transplants, survive past the first year. This contrasts with earlier research from the U.S. and Europe, which showed lower one-year survival rates for those with ALF as compared to those with cirrhosis who received transplants.

More recent data from 2012 suggests a more positive outlook, with a survival rate of 79% after one year and a survival rate of 72% at the five-year mark. To predict the outcome for ALF patients, doctors often use several criteria. The most common ones are the King’s College Criteria for ALF resulting from an overdose of acetaminophen and ALF not linked to acetaminophen.

Other helpful criteria for making a prognosis include the Clichy criteria, which consider the presence of hepatic encephalopathy (brain damage caused by liver failure) and a Factor V level (a protein necessary for blood to clot properly) lower than 20 to 30% of normal. A MELD score higher than 30 (this measures severity of chronic liver disease) and an Acute Physiology and Chronic Health Evaluation (APACHE) II score above 15 (which measures the severity of disease for patients admitted to the intensive care unit) also aid prognosis.

Frequently asked questions

Acute Liver Failure (ALF) is a serious condition that causes severe dysfunction of the liver in patients without any prior liver disease. It is characterized by sudden, severe liver injury accompanied by encephalopathy and impaired liver function. ALF occurs within 26 weeks or less of falling ill.

Acute Liver Failure (ALF) can occur due to various causes and its occurrence rates vary between developed and developing countries.

Signs and symptoms of Acute Liver Failure (Liver Failure) can include: - Low blood pressure - Changes in mental status - Fever (if the cause is an infection) - Discomfort or pain in the upper right part of the stomach - Symptoms of jaundice (yellowing skin or eyes) - Signs of fluid buildup in the body like swelling.

ALF can be caused by factors such as viral hepatitis, drug-induced hepatitis, oxygen shortage-induced liver injury, unique blood vessel disorders in the liver, Wilson disease, eating poisonous mushrooms, widespread infection, autoimmune liver disease, liver condition during pregnancy, liver complications from a dangerous pregnancy condition, heatstroke, or cancer spreading to the liver.

The doctor needs to rule out the following conditions when diagnosing Acute Liver Failure (Liver Failure): 1. Sudden onset fatty liver during pregnancy 2. Poisoning from Amanita phalloides mushroom 3. Toxins from the Bacillus cereus bacteria 4. Inability to digest fructose (Fructose intolerance) 5. Metabolic disorder affecting the ability to process galactose (Galactosemia) 6. A severe pregnancy complication caused by problems with blood cells called HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome 7. Infections from hemorrhagic viruses such as Ebola, Lassa, and Marburg 8. Unexplained allergic reaction to drugs (Idiopathic drug hypersensitivity) 9. A newborn disease related to excess iron storage (Neonatal iron storage disease) 10. Disorder of the metabolism of the amino acid tyrosine (Tyrosinemia)

The types of tests that may be needed to diagnose Acute Liver Failure (Liver Failure) include: - Blood tests to measure clotting time (INR value), bilirubin levels, aminotransferases levels, platelet and red blood cell counts, blood sugar levels, ammonia levels, and signs of kidney damage - Imaging tests such as abdominal ultrasound, MRI, or CT scan to assess the liver and other organs for conditions like cirrhosis, liver cancer, blood clots, swollen lymph nodes, or an enlarged spleen - Brain imaging (MRI or CT scan) to determine if physical changes in the brain are causing mental status changes - Chest imaging to rule out conditions like fluid overload in the lungs or pneumonia These tests are important for diagnosing and determining the best course of treatment for Acute Liver Failure.

Acute liver failure (ALF) is treated through a comprehensive approach that includes supportive care, managing complications, treating the underlying cause, and potentially considering a liver transplant. Supportive care involves careful monitoring of blood flow, fluid balance, acid-base levels, and electrolytes. Bleeding is a high risk in ALF patients, so monitoring and transfusion of blood products may be necessary. Patients with ALF may develop hepatic encephalopathy, which can lead to swallowing and breathing problems. In these cases, maintaining the airway and preventing brain swelling are important. Nutrition and blood sugar levels should be monitored and treated. Specific treatments are based on the cause of ALF, such as administering activated charcoal and N-acetyl cysteine for acetaminophen-induced ALF, or giving antiviral medications for viral infections. Managing complications, such as kidney failure or metabolic disorders, is crucial. Liver transplantation may be considered for selected patients, but it comes with increased risks.

When treating Acute Liver Failure (ALF), there can be several side effects and complications. These include: - Bleeding: Patients with ALF are at a high risk of bleeding due to poor blood clotting and platelet function. Monitoring for signs of bleeding is important, and transfusion of blood products may be needed in cases of active bleeding or before invasive procedures. - Hepatic Encephalopathy: ALF can cause a brain disorder called hepatic encephalopathy, which can lead to problems with swallowing and breathing. This increases the risk of inhaling food, stomach acid, or saliva into the lungs (aspiration). Steps should be taken to maintain the airway and avoid brain swelling. - Nutritional Issues: Nutrition is vital for patients with ALF, with a target of 1.0 to 1.5 g of protein per kilogram of body weight per day. Low blood sugar (hypoglycemia) should also be monitored and treated. - Complications: ALF can lead to multiple organ dysfunction, including kidney failure. Vasopressor therapy may be required to address severe low blood pressure, and dialysis might be considered. Infections, such as pneumonia, should be treated with broad-spectrum antibiotics. - Metabolic Disorders: Metabolic disorders like hypoglycemia and hypophosphatemia need management with continuous glucose infusions and aggressive phosphorus supplementation. Seizure-like activity can be treated with medications like phenytoin or benzodiazepines. - Cerebral Edema: Cerebral edema, or brain swelling, is a major concern and the most common cause of death in ALF. Steps should be taken to keep intracranial pressure below 25 mm Hg. - Coagulopathy: ALF is associated with abnormal blood clotting (coagulopathy). Routine correction of coagulopathy is not recommended unless there is overt bleeding or before invasive procedures. - Transplantation: Liver transplantation is an option for selected patients with ALF, but it comes with an increased risk of graft complications. Transplant patients are critically ill and are at greater risk of complications, most commonly from infections and sepsis.

The prognosis for Acute Liver Failure (ALF) has significantly improved over the past 50 years. Currently, it is estimated that over 65% of patients, including those who receive liver transplants, survive past the first year. More recent data from 2012 suggests a survival rate of 79% after one year and a survival rate of 72% at the five-year mark.

A liver transplant specialist.

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