The liver is an incredibly important organ, so liver failure is a very serious condition with widespread consequences. Acute liver failure occurs over days to weeks, most commonly due to acetaminophen (Tylenol/paracetamol) overdose or viruses such as hepatitis B.
What is liver failure?
The liver is a large and important organ in the right side of your belly, just under your lower ribs. It is responsible for countless functions from clearing toxins to processing nutrients to producing vital blood proteins.
As a result, liver failure can cause a wide array of symptoms, but the most common are confusion, bleeding, and yellow skin (known as jaundice). When liver failure occurs rapidly (over days to weeks) in someone with no history of liver disease, it is known as acute liver failure. Many things can cause acute liver failure but the most common are acetaminophen (Tylenol/paracetamol) overdose and viral infections such as hepatitis B.
Liver failure is a very serious condition which usually requires admission to an intensive care unit. Some cases resolve with time and supportive care, though many of those who suffer acute liver failure will require a liver transplant.
Acute liver failure is a very serious disease requiring immediate medical attention. It would be prudent to go to the emergency room immediately.
Symptoms of liver failure
Since the liver performs so many important functions, the symptoms of acute liver failure are somewhat vague and widespread. According to a commonly used definition, acute liver failure specifically describes the presence of several lab abnormalities along with the development of altered mental status. Technically referred to as hepatic encephalopathy, this altered cognition can manifest in a variety of ways, such as:
- Excessive drowsiness, decreased consciousness or difficulty to arouse
- Confusion or disorientation
- Tremor, classically with a flapping motion known as asterixis
- Muscle rigidity or spasm
In addition to cognitive changes, a wide array of other symptoms can be seen in acute liver failure, such as:
- Yellowing of the skin or eyes, known as jaundice
- Right-sided abdominal pain, classically just below the right ribs
- Fatigue and malaise
- Nausea and vomiting
- Loss of appetite
- Abdominal distension caused by fluid in the belly known as ascites
While many of these symptoms are vague and not unique to liver failure, the combination of newly yellow (jaundiced) skin or eyes, abdominal distension and altered consciousness is particularly classic for liver failure.
Causes of liver failure
The most common causes of acute liver failure vary worldwide. In the U.S. and much of Europe, acetaminophen overdose is the most common cause, usually as the result of a suicide attempt. Acetaminophen toxicity is very rare at recommended doses, though accidental overdose can occur when multiple medications are taken which each contain acetaminophen.
In other parts of Europe and most of Asia, viral hepatitis is the leading cause of acute liver failure. In particular, infection with hepatitis A, B and E can all lead to acute liver failure, as can some other viruses such as HIV and members of the herpes virus family. Hepatitis A and E are transmitted via the “fecal-oral route” meaning that the infection comes from contaminated food or drink, or certain sexual practices. Hepatitis B is transmitted by contaminated body fluids, often through injection drug use or unsafe sexual practices. It is also an important infection risk for healthcare workers due to the high rate of infection from accidental needlesticks.
In addition to those more common causes, there is a wide array of rarer conditions which can lead to acute liver failure. A handful of other medications can cause liver failure, as can a wide array of toxins.
- Wilson’s disease: This is an inherited metabolic disorder which can cause chronic liver damage but may first present as acute liver failure.
- Autoimmune hepatitis: This is an uncommon cause of acute liver failure in which the body mistakenly attacks itself.
- HELLP syndrome: In pregnant women, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome is a serious complication which involves concurrent blood cell destruction and liver failure.
- Industrial chemicals
- Poisonous mushrooms: Amanita phalloides look similar to some edible ones.
- Herbal supplements: Liver failure has also been associated with various herbal supplements such as kava and ephedra.
- Illnesses that lead to shock: Acute liver failure can result from almost any cause of severe illness that leads to significant impairment of circulation and dangerous drops in blood pressure (known as shock) such as a heart attack or severe systemic infection.
Treatment options and prevention for liver failure
Regardless of the specific cause, certain steps can be taken to help improve outcomes in any case of liver failure. Whenever possible, those suffering from liver failure should be cared for at an advanced-care hospital capable of performing liver transplantation. While survival varies depending on the cause of liver failure, more than half of people suffering most causes of acute liver failure will require liver transplantation to survive. Transfer to a transplant-capable facility should be performed as soon as possible since transportation becomes more dangerous as the disease progresses.
Close monitoring is another vital part of managing acute liver failure. Typically this means being treated in an intensive care unit and getting very frequent blood samples taken to monitor for disease progression and dangerous complications. These tests are extremely important to guide the medical team’s decisions regarding which interventions will be most helpful. In particular, monitoring will be done to assess for bleeding or clotting, electrolyte imbalances, brain swelling (cerebral edema), infection, and failure of other organs such as the kidneys or lungs. In some cases, a sample of liver tissue (known as a biopsy) will be necessary to determine the exact cause of liver failure.
Two common complications of acute liver failure are low blood pressure (hypotension) and swelling of the brain tissue (cerebral edema). Medications known as vasopressors or simply “pressors” are often needed to maintain blood pressure within safe ranges. Several medications may be used to treat brain swelling, as can drains or shunts which serve to release pressure built up within the skull.
For many years, research has been conducted to design a machine which can act as an artificial liver, similar to the way dialysis works in kidney failure. These are known variously as extracorporeal liver support, bioartificial liver support, or hepatic assist devices. Unfortunately, such a machine has proved extremely challenging to design, largely because of the enormous breadth of functions performed by the liver. Some studies have shown significantly improved survival with the use of such devices, while other studies have not. As of 2018, guidelines from professional societies such as the American Gastroenterological Association, the American Association for the Study of Liver Diseases, and the European Association for the Study of the Liver all recommend that such liver support devices only be used in the context of a clinical trial. They do not consider there to be sufficient evidence to recommend the use of such devices as part of routine care of liver failure.
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Treatment for specific causes
As with many conditions, treatment of acute liver failure varies depending on the specific cause. For acetaminophen toxicity, a medication known as n-acetylcysteine (NAC) has long been known to protect the liver and improve survival. However, it is only effective if administered promptly, ideally within hours of the overdose. More recently, some research has suggested that NAC may help with liver failure of other causes as well, though this data has been controversial. Therefore most guidelines currently recommend the use of NAC only for liver failure caused by drug toxicity, or as part of a clinical trial.
For liver failure due to infection with one of the hepatitis viruses, antiviral medications are sometimes used. However, evidence for their efficacy is conflicted and they are not universally recommended. Similar conflicts exist regarding the evidence for treatment of autoimmune hepatitis, mushroom poisoning, and many other causes of acute liver failure. In very broad terms, most instances of liver failure that do not resolve with supportive care will require liver transplantation.
Prevention of acute liver failure varies depending on the particular cause.
- Completely preventable cases: Some things, like acetaminophen overdose, can be completely avoided by only taking medications at the recommended doses and frequency.
- Not preventable cases: Other causes such as Wilson’s disease and autoimmune hepatitis are all but impossible to prevent, but thankfully these conditions are quite rare.
- Prevention for hepatitis A and E: Prevention is most relevant for acute liver failure caused by the hepatitis family of viruses. Since they are transmitted through fecal matter and contaminated food, hepatitis A and hepatitis E can be prevented with good hand hygiene and sanitation. That means washing hands with soap frequently and thoroughly, particularly when after using the toilet and when preparing food. It is also important to only consume food and water from sources known to be safe.
- Prevention for mushrooms: Avoiding consumption of poisonous mushroom is imperative.
- Prevention for hepatitis B: For hepatitis B, prevention consists primarily of avoiding injection drugs and practicing safe sex.
For any of these conditions, early recognition and treatment are important to help prevent the progression to fulminant liver failure.
When to seek further consultation for liver failure
Liver failure is an extremely serious condition which requires prompt treatment. Untreated liver failure has a very poor prognosis and is often fatal even in a previously healthy person. Acute liver failure, in particular, should be treated as soon as possible, ideally in the intensive care unit at a facility capable of performing liver transplantation. Anyone with symptoms concerning for liver failure, or known exposure such as acetaminophen overdose, should call an ambulance or go to an emergency department immediately.