Liver Failure: Acute and Chronic Damage

Liver failure is a potentially life-threatening condition in which the liver is no longer able to service the body's needs. Liver failure develops in stages, causing early-stage signs like nausea and vomiting before progressing to more serious symptoms like ascites (fluid accumulation in the belly) and jaundice (yellowing of the skin and eyes).

The two forms of liver failure are acute liver failure, in which symptoms develop rapidly, usually in people with no preexisting liver disease, and chronic liver failure, in which symptoms develop gradually as a result of cirrhosis. Liver transplantation is often needed to survive.

This article looks at the causes and symptoms of acute and chronic liver failure, including how the conditions are diagnosed and treated.

Acute vs. Chronic Liver Failure 

Liver failure, also known as hepatic failure, occurs when the liver is no longer able to perform vital bodily functions, including:

• Filtering toxins, byproducts, bacteria, and other harmful substances from the blood
• Producing bile, a digestive fluid that the body needs to break down fat
• Processing, storing, and secreting glucose (blood sugar) as the body requires
• Creating clotting factors that the body needs to clot blood
• Regulating the production of thrombopoietin, which stimulates platelet production

When these and other functions cease, the accumulative effect can be life-threatening, causing other organs (like the pancreas and kidneys) to gradually shut down as well. This can happen with both acute liver failure and chronic liver failure.

Although acute and chronic liver failure are both associated with a high mortality (death) rate, the causes of organ failure are very different.

Acute Liver Failure

Acute liver failure (ALF) is a rare disease. There are only 2,000 to 3,000 cases reported in the United States each year. It typically affects people with no prior liver disease, causing the rapid loss of liver function within days or weeks. In some cases, ALF can become life-threatening within hours if left untreated.

The speed at which ALF progresses can vary. Hyperacute AFL is when symptoms develop within less than 10 days, fulminant ALF is when symptoms appear within 10 to 30 days, and subacute hepatic failure is the onset of symptoms within five to 24 weeks.

The causes of ALF are many but ultimately involve either agent, infection, or disease that severely injures the liver or structures servicing the liver.

Examples include:

• Tylenol (acetaminophen) poisoning: This is the most common cause of ALF. Failure can occur after one very large dose or when overusing the drug over several days.
• Hepatitis A, B, and E: These three forms of viral hepatitis can cause liver inflammation severe enough during early infection to cause liver failure.
• Prescription drugs: Certain hepatotoxic drugs (meaning those toxic to the liver) can cause ALF if overused. These include chemotherapy, antiepileptic drugs, and antibiotics (antibacterial drugs) like flucloxacillin.
• Toxic substances: Many herbal drugs like kava, skullcap, and ephedra are known to be liver poisons. as are the recreational drug ecstasy and the wild death cap mushroom, Amanita phalloides.
• Autoimmune hepatitis: This is a disease in which the immune system targets and attacks healthy liver cells. Severe episodes can lead to ALF.
• Preeclampsia: This is a pregnancy complication characterized by dangerously high blood pressure. Severe cases can cause the liver to rupture, leading to ALF.
• Shock: This is when a steep drop in blood pressure deprives organs of the oxygen they need to survive. When the liver is involved, it can lead to ischemic hepatitis (also known as shock liver).
• Budd-Chiari syndrome: This is a rare disorder that causes blockages in the veins of the liver, leading to deterioration of liver function.
• Wilson's disease: This is an inherited disorder that causes copper to accumulate in the liver and other organs. Over time, the accumulation can cause the liver to shut down.
• Cancer: Lymphoma, a type of blood cancer, can cause hepatomegaly (an enlarged liver) and ALF in rare cases. Metastatic liver cancer (caused when cancer spreads to the liver) can do the same.

Chronic Liver Failure

Chronic liver failure (CLF) is the end stage of chronic liver disease (CLD). It is caused by cirrhosis, the gradual loss of liver function due to progressive scarring of the liver.

If your liver is still functional, you are said to have compensated cirrhosis. But if the damage progresses to where the liver is no longer functional, you are said to have decompensated cirrhosis. Decompensated cirrhosis, in turn, can lead to liver failure and death.

There are several key causes of cirrhosis:

• Alcoholic liver disease: This is liver damage that occurs when excessive alcohol use causes the buildup of fat in the liver, which, over time, leads to liver swelling and fibrosis (scarring).
• Chronic hepatitis B and C: This is when hepatitis B or hepatitis C do not spontaneously clear but instead persist, causing increasing damage to the liver.
• Metabolic dysfunction-associated steatohepatitis (MASH): Formerly known as nonalcoholic steatohepatitis (NASH), this is the buildup of liver fat due to conditions like obesity and diabetes.
  

CLF is far more common than ALF, with an estimated 4.5 million people in the United States currently living with the disease. Of these, roughly 50,000 die of cirrhosis each year.

Liver Failure Stages and Progression

Liver failure progresses in stages. With acute liver failure, the onset of symptoms is typically swift and severe. With chronic liver failure, the symptoms may be largely unnoticed in the early stages and only become apparent once decompensation occurs.

Although the rate of progression can vary, acute and chronic liver failure develops in four characteristic stages, known as the latency, prodromal, and symptomatic stages.

Latency Stage

Latency refers to the period in which a disease is asymptomatic (without symptoms) but can be detected with diagnostic tests.

The duration of latency can vary, as follows:

• With ALF, the latency period can last anywhere from a few days to several months, but it is rarely longer than six months.
• With CLF, the latency period prior to decompensated cirrhosis may be as short as six months or last for many years.

Prodromal Stage

Prodrome refers to early nonspecific, generalized, or vague symptoms that develop before the characteristic symptoms of a disease become apparent. Many of these symptoms are subclinical, meaning that they are not readily observable.

With liver failure, early prodromal symptoms may include:

• Fatigue
• Weakness
• Nausea
• Loss of appetite
• Joint achiness
• Malaise (a general feeling of unwellness)
• Discomfort or pressure in the upper right abdomen

These symptoms can easily be mistaken for other causes, including dyspepsia (upset stomach) and gastroenteritis (stomach flu).

Symptomatic Stage

Symptoms of liver failure are initially due to the buildup of waste products like bilirubin in the bloodstream and the depletion of bile and clotting factors from the liver.

Over time, other organs (like the kidneys, intestines, and brain) can start to malfunction, leading to progressively worsening symptoms.

Notable symptoms include:

• Dark urine
• Clay-colored stool
• Vomiting
  
• Pruritus (itching)
• Severe upper-right abdominal pain
• Jaundice (yellowing of the skin and eyes)
  
• Peripheral edema (swelling of the feet and ankles due to fluid overload)
• Ascites (a distended belly due to accumulation of fluid)
  

Complications of Liver Failure

The failure of the liver exposes the body to toxins and changes blood circulation throughout the body, placing undue pressure on organs like the brain, kidneys, intestines, and lungs.

This can lead to potentially serious complications like:

• Variceal hemorrhage: Bleeding in the digestive tract caused by increased blood pressure
• Anemia: A drop in red blood cell numbers caused by bleeding in the digestive tract
• Acute kidney failure: Caused by increased blood pressure exerted on the kidneys
• Hepatopulmonary syndrome: Breathing problems caused by high blood pressure in the lungs

Hepatic Encephalopathy

One of the most dread complications of liver failure is hepatic encephalopathy. This occurs when waste products like ammonia cause the swelling of the brain (cerebral edema) and a cascade of neurological and psychiatric symptoms, such as:

• Mental confusion
• Forgetfulness
• Mood swings
• Changes in behavior
• Disorientation
• Loss of fine motor skills, like writing
• Slurred speech
• Tremors or twitching
• Delirium
• Seizures
• Loss of consciousness
• Coma

In people with acute or chronic liver failure, cerebral edema is associated with a high risk of death and an increased likelihood of a liver transplant.

How Do You Know Your Liver Is Failing?

If liver failure is suspected, your healthcare provider will start by reviewing your medical history. They will want to know what medications you may take, how much alcohol you drink, and your personal and family history of liver disease, among other things.

A physical exam will also be performed to look for signs of liver failure, such as upper-right abdominal pain, easy bruising, yellowing of the eyes or skin, or a characteristic "fruity breath" caused by the buildup of ammonia (known as fetor hepaticus).

Based on the initial findings, your healthcare provider may order tests and procedures like:

• Complete blood count (CBC): This is a battery of blood tests that can detect imbalances in red blood cells, white blood cells, and platelets commonly seen with liver failure.
• Liver functions tests (LFTs): This is another battery of blood tests that detect liver injury or inflammation based on increased liver enzymes.
• Prothrombin time (PT): This is a blood test that can detect blood clotting problems based on the clotting time of a sample of blood.
• Viral hepatitis serology: This is a panel of blood tests that screen for hepatitis A, B, and C.
• Abdominal imaging: This includes an abdominal ultrasound or computed tomography (CT) scan to check for hepatomegaly, variceal bleeding, or a blocked hepatic artery or vein.
• Brain imaging; This includes a magnetic resonance imaging (MRI) scan or CT scan to check for signs of brain swelling or bleeding.
• Liver biopsy: This involves the extraction of liver tissues to check for signs of lymphoma, Wilson's disease, autoimmune hepatitis, or cancer.

Treating Liver Failure

People with liver failure are typically treated in the intensive care unit (ICU) of a hospital, ideally one that specializes in liver transplants should the condition become serious.

During hospitalization, intravenous (IV) fluids and medications are administered to avoid complications such as respiratory distress, hypoglycemia (low blood sugar), seizures, infections, or kidney failure.

Once stabilized, specific treatments are prescribed based on the known or suspected cause. Examples include:

• Tylenol overdose: Treated with an antidote called N-acetylcysteine (NAC)
• Acute viral hepatitis: Commonly treated with a seven-day course of the antiviral drug Zovirax (acyclovir)
• Autoimmune hepatitis: Commonly treated with the immunosuppressant drug called Imuran (azathioprine)
• Preeclampsia: Treated with antihypertensive drugs to lower blood pressure 
• Budd-Chiari syndrome: Treated with anticoagulants (blood thinners) and intrahepatic shunts to open blocked blood vessels
• Wilson's syndrome: Commonly treated with therapeutic plasma exchange to reduce copper levels in the blood

Liver Transplantation

With the appropriate treatment of ALF, liver transplantation may not be needed. The same is not true for decompensated cirrhosis in which a liver transplant is needed when complications can no longer be managed.

Because a donor liver is not always available, efforts will be needed to manage the condition until one is found. This may involve:

• Intravenous diuretics and a salt-restricted diet to reduce fluid overload
• Antibiotics, considered a mainstay of treatment for acute hepatic encephalopathy
• A drug called Terlivaz (terlipressin) to help lower blood pressure and the risk of kidney failure
• A hypotonic saline IV drip to ease pressure on the brain

A liver transplant may be needed for severe cases of ALF, particularly if cerebral edema is involved. Given that cerebral edema is the main cause of death in people with ALF, anyone with severe hepatic encephalopathy should be regarded as a candidate for a liver transplant.

Living With Liver Failure

Liver failure is a potentially devastating condition, but with the appropriate treatment, people can survive—and even thrive—for many years.

This is especially true with ALF. Due to advances in early diagnosis and treatment, between 25% and 45% of those who experience ALF do not need a liver transplant. Some people may even experience a complete reversal, given the liver's ability to regenerate itself.

Even so, some individuals will eventually need a transplant if significant damage is done. To delay this, the following steps are recommended to preserve liver function:

• Avoid alcohol (and seek alcohol treatment if you can't stop).
• Maintain a healthy weight.
• Avoid Tylenol or other substances toxic to the liver.
• Get the Twinrix vaccine to prevent hepatitis A and hepatitis B.
• Seek curative treatment for hepatitis C.
• Quit cigarettes, which cause the narrowing and hardening of blood vessels.
• Do regular cardiovascular exercise to help lower blood pressure.
• Eat a heart-healthy, low-fat diet.

The same efforts are recommended even if your odds of future transplant are low.

After a Transplant

If you had a liver transplant, additional steps would be taken to reduce the risk of infection and organ rejection. You would be advised to:

• Take your immunosuppressant drugs as prescribed.
• Stay away from people who are sick.
• Keep up to date with all your recommended vaccinations.
• Avoid raw and undercooked food, including unpasteurized milk.
• Protect yourself from soil exposure by wearing socks, shoes, and gloves.
• Avoid pets such as rodents, reptiles, and birds.
• Use repellents and other protection against ticks and mosquitoes.

Summary

Liver failure is a potentially deadly situation when your liver can no longer service the body's needs. Chronic liver failure can develop slowly with the onset of decompensated cirrhosis. Acute liver failure can happen suddenly with the excessive use of Tylenol, liver infections like hepatitis A and B, or liver diseases like autoimmune hepatitis and Wilson's disease.

Symptoms of liver failure often start subtly with nausea and fatigue before progressing to more severe symptoms like jaundice, ascites, and variceal bleeding. Liver failure can rapidly turn deadly if left untreated and may require a liver transplant to survive.