By Christine Zink, MD 

 Medically reviewed by Jordana Haber Hazan, MD

Hepatitis is inflammation of the liver, either short-term or chronic. Sometimes, hepatitis can be so severe that it leads to liver failure.1

Fulminant hepatitis is a severe form of acute liver failure found in people without prior liver problems or chronic hepatitis.2 The liver failure develops over several weeks and is associated with confusion or coma. People with fulminant hepatitis have a poor prognosis and often do not recover unless they receive a liver transplant.

This article discusses the differences between fulminant hepatitis and regular hepatitis, as well as its causes, symptoms, and treatment.

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FG Trade / Getty Images

Function of the Liver

The liver has many essential functions. In fact, almost all of our blood passes through the liver.3

The liver also:4

  • Helps convert nutrients in the diet into useful substances

  • Converts toxic substances into harmless substances that are eventually eliminated through the bowels

  • Functions as a storage unit for fats and helps break them down to produce energy

  • Breaks down proteins to create the building blocks of cells

  • Produces proteins that are important in blood clotting to stop regular bleeding

When the liver malfunctions, the body suffers from a buildup of toxins, fails at producing needed proteins for other organ systems to work, and cannot remove waste products through the process of metabolism.

What Is Fulminant Hepatitis Compared to Hepatitis?

Fulminant hepatitis is acute liver failure associated with confusion or coma that occurs in a few days to weeks from the inciting event. It occurs in people without prior liver disease.2

Fulminant hepatitis is also known as:

  • Fulminant hepatic failure

  • Acute hepatic necrosis

  • Fulminant hepatic necrosis

The liver is made up of cells called hepatocytes. Hepatitis is inflammation and swelling of the liver that leads to hepatocyte damage and malfunction. 

There are lots of different ways that the liver responds to an injury or event. Sometimes people develop hepatitis quickly, whereas at other times, it can take months or years for the inflammation to develop.

In addition, some forms of hepatitis are mild and short-lived, only lasting a few days or weeks. Other forms, however, may be chronic. Some people can live with mild to moderate liver inflammation for a long time.

Fulminant hepatitis differs in that it is acute, meaning it occurs very quickly. It is also severe to the point that a person develops liver failure.5 It is considered one of the worst kinds of hepatitis.

Alcohol Use and Hepatitis

Fulminant hepatitis is not diagnosed in people who drink large amounts of alcohol. People with liver disease due to alcohol use usually have a long history of drinking and develop hepatitis slowly. 

What Causes Fulminant Hepatitis?

There are many causes of hepatitis. Not all are associated with fulminant hepatitis, but there is a lot of overlap.

The most common causes of fulminant hepatitis are:5

  • Overdose, specifically of Tylenol (acetaminophen)

  • Viral hepatitis (particularly hepatitis B)

Generally, viruses are the most common cause of fulminant hepatitis worldwide, whereas Tylenol overdose is more common in the United States and the United Kingdom.5 Overdose can be both accidental or intentional.

In general, the causes of fulminant hepatitis can be divided into viruses, toxins, and other rare causes.

Viruses

The most common viruses associated with fulminant hepatitis are:5

  • Hepatitis A virus

  • Hepatitis B virus (the leading viral cause of fulminant hepatitis)

  • Hepatitis E virus

  • Varicella-zoster virus (causes chicken pox and shingles)

  • Herpes simplex virus (causes oral herpes and genital herpes)

  • Dengue virus (a mosquito-borne virus)

  • Parvovirus B19 (causes fifth disease)

  • Epstein-Barr virus (a type of herpes virus that can cause mononucleosis)

Usually, when healthcare providers diagnose fulminant hepatitis, they assume hepatitis A, B, or E as the likely cause. Fulminant hepatitis is rarely associated with the other listed viruses.

Fulminant Hepatitis and Hepatitis B Virus

Fulminant hepatitis can develop from acute hepatitis B infection but can also occur in people who have reactivated chronic hepatitis B. Fulminant hepatitis from hepatitis B infection results in death or liver transplantation 80% of the time.5

Toxins/Drugs

The toxins or drugs most associated with fulminant hepatitis include:5

  • Tylenol (acetaminophen) overdose

  • Certain poisonous mushrooms, like Amanita phalloides

  • Certain antibiotics

  • Ecstasy (synthetic drug that alters mood)

  • Antituberculous antibiotics (medicines that treat tuberculosis)

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and Advil or Motrin (ibuprofen)

  • Iron supplement overdose

  • Certain Chinese herbal medicines

  • Chlorpromazine (used to treat psychotic disorders)

  • Ondansetron (anti-nausea medication)

  • Stavudine (used to treat human immunodeficiency virus, or HIV)

Tylenol (acetaminophen) overdose is by far the most common cause of fulminant hepatitis among these toxins.5

Other Causes

Other factors are known to cause fulminant hepatitis as well, including:

  • Wilson’s disease (an inherited disorder in which copper accumulates in the liver)

  • Metastatic cancer (cancer that has spread from one part of the body to elsewhere in the body), leukemia, or lymphoma

  • Autoimmune hepatitis

  • Heatstroke

  • Budd-Chiari syndrome (a blockage of the veins inside the liver)

  • Reye’s syndrome (rare but serious illness that can cause brain and liver damage)

  • Ischemic liver failure due to severe cardiovascular disease or sepsis (severe infection in the blood)

  • HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome during pregnancy

  • Fatty infiltration of the liver

Most Common Causes

In the United States, nearly half of fulminant hepatitis cases are from accidental or intentional Tylenol overdose.5 The next most common cause of fulminant hepatitis is “indeterminate causes,” which means healthcare providers do not find a definite answer. There are some cases of drug-related fulminant hepatitis, hepatitis B- or A-related disease, autoimmune hepatitis, and Wilson’s disease.5 However, all other causes are infrequent.

Symptoms

Fulminant hepatitis is associated with nonspecific symptoms, such as:1

  • Fever

  • Fatigue

  • Loss of appetite

  • Nausea and vomiting

  • Abdominal pain

More specific symptoms that suggest acute liver disease include:1

  • Dark urine

  • Abdominal swelling and distention

  • Clay-colored bowel movements

  • Itching

  • Jaundice (yellowing of skin and whites of the eyes)

  • Confusion or coma

Fulminant hepatitis is diagnosed through a physical exam and laboratory tests evaluating liver function. Healthcare providers also spend time determining the cause of fulminant hepatitis, because knowing the cause influences disease management.

How Is Viral Hepatitis Contracted?

Hepatitis A virus is spread through contact with contaminated food or water. Hepatitis B virus is spread through contact with an infected person’s blood or bodily fluids. The spread of the virus most often occurs from sharing drug needles or through unprotected sex.1

Treatment

Patients with fulminant hepatitis should be managed in a specialty liver transplant center. The goal is to attempt to treat the underlying cause of liver failure. This means giving certain medications or performing special procedures.

The hope is that the treatments will prevent worsening liver failure and needing a liver transplant. 

Tylenol Overdose

An acetaminophen overdose is treated with N-acetylcysteine (NAC). Patients do very well with this treatment if it is started soon after the overdose.

NAC also seems to work in people with other causes of fulminant hepatitis, including other drug-induced disease, autoimmune hepatitis, hepatitis B infection, and acute liver disease for unknown reasons.6

Viral Fulminant Hepatitis

Patients with hepatitis B infection should be treated with an antiviral agent, like lamivudine.7 The drug can prevent the need for liver transplantation. Even if a patient progresses to need a transplant, healthcare providers should still use the antiviral to prevent post-transplant complications from hepatitis B infection.7

Herpes simplex virus fulminant hepatitis should be treated with the antiviral acyclovir. However, fulminant hepatitis from herpes simplex is extremely rare.

Budd-Chiari Syndrome

For Budd-Chiari syndrome, a surgical procedure called a transjugular intrahepatic portosystemic shunt can open the blocked blood vessels to restore blood flow through the liver. However, this often is only a temporary soluton. 

Wilson’s Disease

For Wilson's disease, patients can be treated with plasma exchange, in which the blood is filtered to remove extra copper from the system. However, this is a temporary option.

Other general treatments include:2

  • Maintaining adequate nutrition

  • Preventing bleeding (the liver produces proteins that help with clotting, so patients with liver failure are prone to bleeding)

  • Avoiding infection

  • Avoiding toxic medications that can make confusion worse or affect the kidneys (since liver failure can also lead to kidney damage)

When a Transplant Is Needed

Sometimes, the only treatment for fulminant hepatitis is liver transplantation. A person's prognosis after the transplant depends on:5

  • Their age

  • Cause of liver failure

  • Severity of the disease before the transplant

  • Amount of confusion present in the patient 

  • Effects on other organ systems, like the kidneys

For those who do qualify for a transplant, the chance of survival is excellent, at 92%.8

Prevention and Prognosis

The inciting cause of fulminant liver failure can determine a person’s likelihood of survival.

For instance, people with fulminant hepatitis from hepatitis A infection are more likely to recover spontaneously without a liver transplant. People with a Tylenol overdose and pregnancy-related liver disease also seem to do better.5

In contrast, people with fulminant hepatitis from other toxins or drugs, hepatitis B infection, autoimmune hepatitis, Wilson’s disease, or Budd-Chiari syndrome do not survive long without liver transplantation.5

Prognosis for Fulminant Hepatitis

People with fulminant hepatitis from all causes have about a 75% chance of survival.8 Approximately 56% of people will survive without needing a liver transplant.8 The mortality related to fulminant hepatitis is worse for people over age 40 and under age 10.5

Although some people develop fulminant hepatitis for unknown reasons and not all causes can be avoided, there are ways to prevent fulminant hepatitis.1

  • Avoid taking an overdose of Tylenol

  • Get vaccinated for hepatitis A and hepatitis B viruses.

  • Avoid mild liver disease by limiting your intake of alcohol

Unfortunately, Wilson’s disease and autoimmune hepatitis cannot be prevented.1

Summary

Fulminant hepatitis is a potentially life-threatening condition of acute liver failure that occurs over a few weeks. It is associated with confusion or coma in people who have not had prior liver disease.

There are many causes of fulminant hepatitis, but the two most common are Tylenol (acetaminophen) overdose and viral hepatitis infection. About half of people will have spontaneous recovery with specific treatments for their liver failure. Still, many others will require a liver transplant. Chances of survival—particularly in young people—are good after transplantation. 

 Sources

MedlinePlus. Hepatitis.

Wendon J, Cordoba J, Dhawan A, et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047-1081. doi:10.1016/j.jhep.2016.12.003

Centers for Disease Control and Prevention. The liver.

Institute for Quality and Efficiency in Health Care. How does the liver work.

Ichai P, Samuel D. Etiology and prognosis of fulminant hepatitis in adults. Liver Transpl. 2008;14(S2):S67-S79. doi:10.1002/lt.21612

Lee, William M et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856-864.e1. doi:10.1053/j.gastro.2009.06.006

Miyake Y, Iwasaki Y, Takaki A, et al. Lamivudine treatment improves the prognosis of fulminant hepatitis B. Intern Med. 2008;47(14):1293-9. doi:10.2169/internalmedicine.47.1061

Reuben A, Tillman H, Fontana RJ, et al. Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study. Ann Intern Med. 2016;164(11):724-32. doi:10.7326/M15-2211

By Christine Zink, MD

Dr. Zink is a board-certified emergency medicine physician with expertise in the wilderness and global medicine.