Acute on Chronic Liver Failure (Liver Failure)

What is Acute on Chronic Liver Failure (Liver Failure)?

Acute on chronic liver failure, or ACLF, is a sudden worsening of liver function in a person who already has long term liver disease. This condition often leads to other organs failing, increasing the risk of death.

Regardless of the root cause of the ongoing liver damage, doctors following the course of liver disease often see a pattern. The person first has liver disease without noticeable complications which then, over time, leads to a state called cirrhosis — a severe scarring of the liver. Finally, the liver function worsens to the point where more serious symptoms show up, such as fluid build-up in the body (ascites), yellowing of the skin (jaundice), increased blood pressure in the liver (portal hypertension) which can lead to bleeding, and liver-related brain dysfunction (hepatic encephalopathy).

We talk about type-A ACLF when there is a sudden worsening of liver function in a patient who already has long term liver disease. Type-B ACLF is when this sudden worsening of liver function happens in people with cirrhosis, a severe form of liver disease, while type-C ACLF is when there is a sudden worsening of liver function in people who already have cirrhosis and additional serious symptoms.

What Causes Acute on Chronic Liver Failure (Liver Failure)?

ACLF, or acute-on-chronic liver failure, can occur due to a trigger event in someone who already has a liver condition. Several things can lead to this, from liver-related sources like alcohol damage, drug-induced liver damage, viral hepatitis, lack of oxygen to the liver, or liver surgeries, including a certain procedure known as a transjugular intrahepatic portosystemic shunt (TIPS).

In addition to liver-related issues, non-liver-related factors like bacterial infections and significant surgeries can also play a part. Interestingly, in about 40% to 50% of patients, the trigger event that leads to ACLF is not recognized or found.

What specifically triggers ACLF can vary depending on the region in the world, just like it varies for sudden liver failure. In Western countries, alcohol injury and bacterial infections are most commonly associated with triggering ACLF. In contrast, in Asia, in addition to alcohol injury and bacterial infections, the reactivation of chronic hepatitis B and infections from acute hepatitis A and E are the most common factors.

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

Acute on chronic liver failure (ACLF) accounts for about 5% of all hospital stays due to cirrhosis. When compared to the most common reasons for hospitalization, it puts a greater financial burden on the healthcare system. The average cost of an ACLF hospital stay is three times more than a hospital stay for cirrhosis, and five times more than a hospital stay for congestive heart failure.

The estimated death rate for people with ACLF has improved over time. It went down from 65% in 2001 to 50% in 2011. The current global death rate as reported by the European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF consortium) varies between 30% and 50%. The mortality rates in the U.S., according to the North-American Consortium for the Study of End-Stage Liver Disease (NACSELD), range from 27% to 77% depending on the number of organ failures in patients with a poor liver function.

About 30% of people who were hospitalized for ACLF end up being readmitted within 30 days of their discharge.

Signs and Symptoms of Acute on Chronic Liver Failure (Liver Failure)

If someone is showing signs of acute hepatic decompensation (sudden liver failure), doctors will gather certain information to help them understand what might have caused it. They talk to the patient and their family, and look through their medical records to find out:

If the patient has been previously diagnosed with a chronic liver condition, and if so, how much liver scarring (fibrosis) or hardening (cirrhosis) is present
Whether the patient has a history of liver failure before
What other long-term health problems they have
How the patient’s symptoms developed and when they started, including things like general illness, signs of fluid retention, gastrointestinal bleeding, abdominal pain, or changes in mental state
Whether the patient uses harmful substances or has engaged in risky behaviors, like heavy drinking or drug use
Any recent changes in their medications, or if they’ve been using any substances that could harm the liver, including herbal products or over-the-counter painkillers/sedatives
Whether they’ve recently traveled, which could expose them to different types of diseases
If they’ve recently undergone any surgeries, including a TIPS procedure which is a treatment for certain types of liver disease

Doctors will also look for certain signs during a physical exam, including low blood pressure, confusion or other changes in mental state, yellowing of the skin or eyes (jaundice), involuntary flapping or tremor of the hands (asterixis), fever, pain and tenderness in the upper right part of the abdomen, feelings of sickness (nausea), and signs that the body is retaining fluid.

Testing for Acute on Chronic Liver Failure (Liver Failure)

Patients with acute hepatic decompensation, a sudden and severe worsening of liver function, often present certain symptoms and lab results. These can include a prolonged INR (a measure of blood clotting time) of 1.5 or higher, increased levels of bilirubin and aminotransferases (liver enzymes), low platelet count and anemia, low blood sugar, high ammonia level, signs of acute kidney injury (such as high creatinine level), and imbalances in electrolytes (like low levels of potassium or phosphorus).

Medical imaging, like scans or X-rays, may be needed to support the observable symptoms and confirm any infection, organ involvement, or organ failure. This could involve imaging of the brain, chest, abdomen, and pelvis. Abdominal imaging, in particular, is crucial to identify signs of high blood pressure in the veins to your liver, liver cancer, blood clot, swollen lymph nodes, or a large spleen. An abdominal ultrasound with Doppler may be considered for patients who may also have kidney injury or vascular thrombosis, which is a blood clot in the vessels. Brain scans can help rule out any physical causes for changes in mental status, and chest imaging can exclude conditions like fluid in the lungs or pneumonia.

Grading Acute-on-chronic liver failure (ACLF) is a way doctors can determine the severity of the condition, which can help predict the patient’s outcome. It’s been validated in various studies and is split into three grades:

– Grade-1 ACLF: This is characterized by a failure in one organ (such as renal, liver, coagulation, circulatory, or lung failure). It may include a serum creatinine level (a measure of kidney function) of 1.5 to 1.9 mg/dL and/or a mild to moderate degree of hepatic encephalopathy (brain trouble due to liver dysfunction). It can also be diagnosed if there’s a brain failure with a serum creatinine level of 1.5 to 1.9 mg/dl.

– Grade-2 ACLF: This is diagnosed when there is a failure in two organs, regardless of which ones.

– Grade-3 ACLF: This diagnosis applies when there is failure in three or more organs, no matter which ones they are.

Treatment Options for Acute on Chronic Liver Failure (Liver Failure)

The aim in treating acute-on-chronic liver failure (ACLF) involves avoiding the factors that could worsen liver function, providing general supportive care, beginning appropriate treatments as soon as possible, and managing any complications that arise. Determining the need for liver support or possible transplant is also vital in managing ACLF. Ideally, patients should be treated at a healthcare center equipped to perform liver transplants.

To avoid worsening liver function, measures include looking out for and treating any infection quickly, maintaining control of hepatitis B and C viruses, and using intravenous albumin for patients with specific bacterial infections. Particularly, people with severe alcohol-induced hepatitis can benefit from a combination of two drugs, Pentoxifylline and N-acetylcysteine, which can help prevent serious kidney complications.

For general care, it’s crucial to regularly monitor blood flow and balance of body fluids, blood acidity, and salt levels, and ensuring that the brain and kidneys receive enough blood supply. Blood clotting should be monitored due to poor platelet function and any signs of liver disease affecting the brain (hepatic encephalopathy) should be watched for to protect the patient from choke hazards which might require breathing tube insertion.

When the cause of ACLF is known, specific treatment options are available. These include supportive care for hepatitis A and E related ACLF as there is currently no effective antiviral treatments. However, for acute or reactivated hepatitis C or B, antivirals or nucleos(t)ide analogs can be administered respectively.

When complications arise, every effort should be made to avoid the progression of organ dysfunction. Kidney failure may present due to dehydration, damage of kidney tissue, or hepatorenal syndrome. Vasopressor therapy could help manage severe low blood pressure and kidney replacement may be considered if liver transplant is on the cards. Kidney replacement therapy is preferred over blood filtration (hemodialysis) in critically ill patients.

Sepsis, a severe reaction to infection, should be addressed with broad-spectrum antibiotics. In all patients, metabolic disorders and cerebral edema (swelling in the brain) should be monitored and managed carefully.

Hypoglycemia and various electrolyte imbalances are expected due to liver failure and should be continuously treated. Impaired mental state or seizures could indicate life-threatening complications and should be managed promptly.

The progression of a patient’s condition during their hospital stay can dictate whether they may need a liver transplant. Although liver transplants are the only definitive treatment for ACLF, only 10-25% of those on the waitlist get to receive it, while 50-75% may die waiting. Devices that can assist liver function have been tested in clinical trials but have not significantly improved survival rates.

When assessing possible health conditions, the following could be considered:

Overdose of Acetaminophen (paracetamol)
A special liver condition happening during pregnancy (Acute Fatty Liver of Pregnancy)
Poisoning from a specific type of mushroom (Amanita Phalloides)
Poisoning from a bacterium called Bacillus Cereus
A liver condition that prevents bile from flowing properly (Cholestasis)
Serious diseases caused by viruses such as Ebola, Lassa, or Marburg
A genetic disorder affecting how your body processes a sugar called galactose (Galactosemia)
A severe pregnancy complication marked by liver damage and high blood pressure (HELLP Syndrome)
Excessive breakdown of red blood cells (Hemolysis)
Overreaction of the immune system to an allergen (Hypersensitivity)
A rare disease in newborns caused by too much iron (Neonatal Iron Storage Disease)
Severe inflammation of the liver (Severe Acute Hepatitis)
A genetic disorder affecting how the body processes an amino acid called tyrosine (Tyrosinemia)

It’s crucial for medical professionals to accurately diagnose the condition by considering all these possibilities and conducting the necessary tests.

What to expect with Acute on Chronic Liver Failure (Liver Failure)

The CLIF organ failure score is a tool used to predict the chances of survival in patients suffering from chronic liver failure (ACLF). Basically, the higher the score (which indicates multiple organ failures), the higher the risk. If a patient’s CLIF score is above 64, doctors immediately consider liver transplantation as an option.

The cause of the triggering event that leads to ACLF does not affect the prognosis – or what doctors can predict about the outcome of the disease. Infections are the most common cause of ACLF, and these patients are often removed from the liver transplant list, resulting in worse health outcomes. Also, patients with respiratory failure generally have the poorest outcomes.

It’s important to know that ACLF is a condition that can get better, get worse, or evolve slowly over time. This fluctuating nature of the syndrome provides a possible window of opportunity for a liver transplant.

Frequently asked questions

Acute on chronic liver failure, or ACLF, is a sudden worsening of liver function in a person who already has long term liver disease.

Acute on chronic liver failure (ACLF) accounts for about 5% of all hospital stays due to cirrhosis.

Signs and symptoms of Acute on Chronic Liver Failure (Liver Failure) include: - Low blood pressure - Confusion or other changes in mental state - Yellowing of the skin or eyes (jaundice) - Involuntary flapping or tremor of the hands (asterixis) - Fever - Pain and tenderness in the upper right part of the abdomen - Feelings of sickness (nausea) - Signs that the body is retaining fluid In addition to these signs and symptoms, doctors will gather certain information to help them understand what might have caused the liver failure. They will talk to the patient and their family, and look through their medical records to find out if the patient has been previously diagnosed with a chronic liver condition, the extent of liver scarring or hardening, whether the patient has a history of liver failure before, and what other long-term health problems they have. Doctors will also inquire about how the patient's symptoms developed and when they started, including any general illness, signs of fluid retention, gastrointestinal bleeding, abdominal pain, or changes in mental state. They will also ask about the patient's substance use or engagement in risky behaviors, recent changes in medications or use of substances that could harm the liver, recent travel history, and any recent surgeries, including a TIPS procedure.

ACLF can occur due to a trigger event in someone who already has a liver condition. Several things can lead to this, including liver-related sources like alcohol damage, drug-induced liver damage, viral hepatitis, lack of oxygen to the liver, or liver surgeries. Non-liver-related factors like bacterial infections and significant surgeries can also play a part. In some cases, the trigger event is not recognized or found. The specific triggers for ACLF can vary depending on the region in the world.

The doctor needs to rule out the following conditions when diagnosing Acute on Chronic Liver Failure (Liver Failure): 1. Overdose of Acetaminophen (paracetamol) 2. A special liver condition happening during pregnancy (Acute Fatty Liver of Pregnancy) 3. Poisoning from a specific type of mushroom (Amanita Phalloides) 4. Poisoning from a bacterium called Bacillus Cereus 5. A liver condition that prevents bile from flowing properly (Cholestasis) 6. Serious diseases caused by viruses such as Ebola, Lassa, or Marburg 7. A genetic disorder affecting how your body processes a sugar called galactose (Galactosemia) 8. A severe pregnancy complication marked by liver damage and high blood pressure (HELLP Syndrome) 9. Excessive breakdown of red blood cells (Hemolysis) 10. Overreaction of the immune system to an allergen (Hypersensitivity) 11. A rare disease in newborns caused by too much iron (Neonatal Iron Storage Disease) 12. Severe inflammation of the liver (Severe Acute Hepatitis) 13. A genetic disorder affecting how the body processes an amino acid called tyrosine (Tyrosinemia)

The types of tests that are needed for Acute on Chronic Liver Failure (Liver Failure) include: - Lab tests: These may include measuring levels of bilirubin, aminotransferases, platelet count, blood sugar, ammonia, creatinine, and electrolytes. - Imaging tests: Medical imaging such as scans or X-rays may be needed to support observable symptoms and confirm any infection, organ involvement, or organ failure. This could involve imaging of the brain, chest, abdomen, and pelvis. - Abdominal ultrasound with Doppler: This may be considered for patients who may also have kidney injury or vascular thrombosis. - Grading Acute-on-chronic liver failure (ACLF): Doctors may use a grading system to determine the severity of the condition, which can help predict the patient's outcome. This involves assessing the failure of different organs and measuring serum creatinine levels. - Specific tests for known causes: If the cause of ACLF is known, specific treatment options may be available, such as antiviral treatments for hepatitis C or B.

The treatment for Acute on Chronic Liver Failure (ACLF) involves avoiding factors that worsen liver function, providing general supportive care, initiating appropriate treatments as soon as possible, and managing any complications that arise. It is important to determine the need for liver support or possible transplant. Measures to avoid worsening liver function include treating infections promptly, controlling hepatitis B and C viruses, and using intravenous albumin for specific bacterial infections. General care includes monitoring blood flow, body fluid balance, blood acidity, salt levels, and ensuring adequate blood supply to the brain and kidneys. Specific treatment options are available depending on the cause of ACLF. Complications should be managed to prevent organ dysfunction, and sepsis should be addressed with broad-spectrum antibiotics. Continuous treatment is necessary for hypoglycemia and electrolyte imbalances. The progression of the patient's condition may determine the need for a liver transplant, although the availability of liver transplants is limited.

The text does not mention any specific side effects when treating Acute on Chronic Liver Failure (ACLF). However, it does mention various complications that can arise and need to be managed, such as infection, kidney failure, sepsis, metabolic disorders, cerebral edema, hypoglycemia, electrolyte imbalances, impaired mental state, and seizures. These complications can have serious consequences and should be addressed promptly. Additionally, the text mentions that liver transplants, which are the only definitive treatment for ACLF, have a low rate of availability, with only 10-25% of those on the waitlist receiving a transplant.

The prognosis for Acute on Chronic Liver Failure (ACLF) varies depending on the number of organ failures and the severity of liver function. The estimated death rate for ACLF ranges from 30% to 50% globally, and in the U.S., it can range from 27% to 77% depending on the number of organ failures. Patients with a CLIF organ failure score above 64 are immediately considered for liver transplantation.

A hepatologist or a gastroenterologist.