Acute on Chronic Liver Failure
Acute on chronic liver failure is a serious medical condition where the liver suddenly stops working properly in people who already have long-term liver disease. This sudden breakdown can happen quickly and affects not only the liver but also other vital organs in the body, making it a life-threatening emergency.
Table of contents
- What is Acute on Chronic Liver Failure?
- How Does This Condition Differ from Other Types of Liver Problems?
- Signs and Symptoms
- What Triggers This Condition?
- What Happens in the Body?
- How is it Diagnosed?
- Severity Levels
- Treatment and Management
- Outlook and Survival
- Prevention Strategies
What is Acute on Chronic Liver Failure?
Acute on chronic liver failure, often shortened to ACLF, is a distinct medical condition that develops when someone with ongoing liver disease experiences a sudden and severe worsening of their condition[1]. This is not just a gradual decline but rather a rapid breakdown that happens over days or weeks[2].
The condition is characterized by sudden failure of the liver combined with failure of one or more other organs in the body. These organ failures develop quickly and create a dangerous situation with high short-term death rates[1][4]. The liver is no longer able to perform its essential functions, and the problems spread beyond just the liver itself.
Different medical organizations around the world have created slightly different definitions of this condition. The Asian Pacific Association for the Study of the Liver focuses on liver-centered problems and includes patients who may not yet have severe scarring of the liver. The North American Consortium concentrates on patients who already have cirrhosis (severe liver scarring) and then develop failures in other organs. The European Association for the Study of the Liver takes a broader approach, considering both liver and non-liver triggers and looking at six different organ systems that might fail[1][4].
How Does This Condition Differ from Other Types of Liver Problems?
It’s important to understand how acute on chronic liver failure differs from other liver conditions. Acute liver failure happens suddenly in someone who previously had a healthy liver, usually due to poisoning or a severe viral infection. This type occurs within days or weeks in people with no prior liver disease[5].
Chronic liver failure is the end stage of long-term liver disease that develops gradually over months or years. It follows cirrhosis, where scar tissue has built up over time and prevents the liver from functioning properly[11][14].
Acute on chronic liver failure sits between these two conditions. It occurs in patients who already have chronic liver disease or cirrhosis, but then something triggers a sudden, rapid decline. Unlike simple acute decompensation of cirrhosis, which is a general worsening of end-stage liver disease, acute on chronic liver failure is specifically characterized by massive inflammation throughout the body and multiple organ failures[3][8].
Signs and Symptoms
People with acute on chronic liver failure can experience a wide range of symptoms that affect many parts of the body. The condition often begins with general symptoms such as pain in the upper right part of the belly, extreme tiredness, nausea, vomiting, and loss of appetite[11][14].
As the condition progresses, more specific signs of liver damage appear. Jaundice, which is yellowing of the skin and the whites of the eyes, develops as bile and other toxins build up in the blood. The abdomen may become swollen with fluid, a condition called ascites. Dark-colored urine is another common sign[5][11].
Mental symptoms can occur when the liver fails to remove toxins from the blood, leading to hepatic encephalopathy. This can cause confusion, disorientation, drowsiness, and changes in personality or behavior. Some people develop tremors or a flapping motion of the hands called asterixis[5][8].
When other organs begin to fail, additional symptoms appear. Kidney failure may cause decreased urination and fluid buildup. Problems with blood circulation can lead to dangerously low blood pressure. Breathing difficulties may develop if the lungs are affected. Fever often indicates an infection, which is a common trigger of this condition[8].
What Triggers This Condition?
Acute on chronic liver failure can be triggered by various events in people who already have underlying liver disease. The most common trigger is bacterial infection, which occurs in many patients[3][4]. These infections can develop in different parts of the body and overwhelm the already weakened liver.
Bleeding, particularly from enlarged veins in the esophagus called varices, can precipitate the condition. Alcohol-associated hepatitis, which is inflammation of the liver caused by heavy alcohol use, is another important trigger[3].
Viral infections can also spark acute on chronic liver failure. Acute hepatitis A or hepatitis E infection may trigger the condition. In areas where hepatitis B is common, reactivation of this virus is frequently responsible[4].
Reduced blood flow to the liver, known as hepatic ischemia, can cause the sudden deterioration. Importantly, in more than 40 percent of patients, doctors cannot identify a specific trigger event, yet the condition still develops[3].
What Happens in the Body?
The underlying process that drives acute on chronic liver failure is complex and involves intense inflammation throughout the entire body. In people with cirrhosis, the liver’s normal structure is disrupted, creating increased pressure in the blood vessels that supply it, a condition called portal hypertension. This increased pressure damages the gut lining, making it easier for bacteria and bacterial products to pass through[3].
When bacteria or bacterial components called pathogen-associated molecular patterns cross from the intestine into the body, they trigger a strong immune response. Additionally, damaged cells release substances called damage-associated molecular patterns. Together, these create an intense wave of inflammation that spreads throughout the body[2][3].
In patients with cirrhosis, there is already a background state of chronic immune system problems called cirrhosis-associated immune deficiency. When the acute trigger occurs on top of this, the immune system can become overactivated and then exhausted, similar to what happens in severe sepsis. This is sometimes called immune paralysis or immune exhaustion[3].
The severe inflammation causes multiple problems. It can damage tissues directly through immune system attacks, reduce blood flow to organs causing tissue hypoperfusion, and impair the function of mitochondria, which are the energy-producing structures inside cells. The combination of these effects leads to organ failures throughout the body[2][3].
How is it Diagnosed?
Diagnosing acute on chronic liver failure requires careful evaluation of patients who have underlying liver disease and present with sudden worsening of their condition. The diagnosis is based on specific criteria that assess both liver function and other organ systems[1].
Blood tests play a crucial role in diagnosis. Doctors measure liver function through tests that check levels of bilirubin (a waste product processed by the liver), albumin (a protein made by the liver), and clotting factors like INR (international normalized ratio). These help determine how well the liver is working[8].
To evaluate other organs, additional blood tests measure kidney function through creatinine and blood urea nitrogen (BUN). Blood tests also check sodium levels, platelet counts, and markers of infection or inflammation. Blood gases may be analyzed to assess acid-base balance and lactate levels[8].
According to the European criteria, six organ systems are assessed: the liver itself, kidneys, brain, blood clotting system, circulation, and lungs. The evaluation uses a specialized scoring system called the CLIF-C Organ Failure score, which is a modified version of the Sequential Organ Failure Assessment (SOFA) score[4][8].
For the liver, bilirubin levels are measured. Kidney function is assessed through creatinine levels. Brain function is evaluated by checking for hepatic encephalopathy using a grading system. Blood clotting is measured through INR. Circulation is assessed by blood pressure and the need for medications to support it. Lung function is evaluated by oxygen levels in the blood and whether mechanical breathing support is needed[8].
Severity Levels
Acute on chronic liver failure is classified into different grades based on the number and type of organ failures present. This grading helps doctors predict outcomes and make treatment decisions[4].
Grade 1 ACLF includes patients with single kidney failure, or patients with single failure of another organ (liver, circulation, lungs, or brain) combined with kidney or brain problems that don’t quite meet the criteria for full failure[4].
Grade 2 ACLF is diagnosed when two organs have failed[4].
Grade 3 ACLF is the most severe level and occurs when three or more organs have failed[4].
Each increasing grade corresponds to higher short-term death rates. Patients with Grade 1 ACLF have approximately 22 percent mortality at 28 days. This increases to higher rates for Grade 2, and Grade 3 patients face mortality rates as high as 76 percent at 28 days[3].
The CLIF-C ACLF score combines organ failure measurements with age and white blood cell count to calculate an overall score that helps predict survival and guide decisions about treatment intensity, including whether liver transplantation should be considered[8].
Treatment and Management
Currently, there is no specific cure for acute on chronic liver failure other than liver transplantation. Management focuses on supportive care for failing organs and treating any identified triggers[2][10].
Patients often require intensive care in specialized units. If an infection triggered the condition, appropriate antibiotics are given. When bleeding has occurred, measures are taken to stop it and replace lost blood[1].
Kidney support may be needed through renal replacement therapy or dialysis when the kidneys fail. Medications called vasopressors may be necessary to maintain adequate blood pressure when circulation fails. If breathing becomes severely impaired, mechanical ventilation might be required[1][10].
Fluid management is carefully balanced—too much fluid can worsen swelling and lung problems, while too little can reduce blood flow to organs. Nutritional support is important, as patients with liver failure have increased metabolic needs[1].
For hepatic encephalopathy, medications like lactulose or rifaximin may be used to reduce toxin levels in the blood. Close monitoring for infections is essential, as these patients have weakened immune systems[10].
Various bridging strategies and artificial liver support systems have been studied, though none has become standard treatment. These include devices that temporarily perform some liver functions while waiting for transplantation or recovery[10].
Liver transplantation remains the only definitive treatment for many patients with acute on chronic liver failure. Studies have shown that while these patients face high risk while waiting for a transplant, their survival rates after receiving a transplant are good, making them suitable candidates. However, not all patients are eligible due to factors like uncontrolled infections or other medical contraindications[10].
Outlook and Survival
Acute on chronic liver failure carries a very high risk of death in the short term. The outlook depends heavily on the number of failing organs and the grade of ACLF[1][2].
Without liver transplantation, mortality rates are substantial. Even with the best supportive care, patients face high 28-day death rates that increase with each grade of severity. The condition represents a dynamic situation where patients can sometimes improve with treatment of the precipitating cause and supportive care, but many will continue to deteriorate[2][4].
For patients who receive a liver transplant, the prognosis improves significantly, with good long-term survival rates. However, the challenge is identifying appropriate candidates and having a donor liver available in time[2][10].
Some patients who survive the acute episode may have ongoing organ dysfunction or progress to end-stage liver disease requiring eventual transplantation. The recovery process can be prolonged and may require extended rehabilitation[10].
Prevention Strategies
Preventing acute on chronic liver failure focuses on managing the underlying chronic liver disease and avoiding known triggers. For patients with known liver disease, regular medical follow-up is essential[1].
Vaccination against hepatitis A and hepatitis B is important, as these viral infections can trigger acute on chronic liver failure. Avoiding alcohol is critical for all patients with chronic liver disease, especially those with alcohol-related liver damage. Even small amounts of alcohol can cause further harm to an already damaged liver[1].
Patients should avoid medications and substances that can damage the liver, called hepatotoxic agents. This includes certain over-the-counter medications and herbal supplements. Before taking any new medication, patients should consult their healthcare provider[1].
Preventing infections is crucial since they are the most common trigger. This includes prompt treatment of any infections, good hygiene practices, and sometimes preventive antibiotics in high-risk situations. Early recognition and treatment of complications like bleeding can help prevent progression to acute on chronic liver failure[1][10].
Regular monitoring by healthcare providers allows for early detection of worsening liver function, enabling interventions before acute on chronic liver failure develops. Patients should seek immediate medical attention if they develop symptoms like increasing confusion, yellowing of the skin, fever, or worsening abdominal swelling[10].
- Liver
- Kidneys
- Brain
- Lungs
- Circulatory system
- Blood clotting system
