What Is Hepatitis D?

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Hepatitis D is a type of viral hepatitis that affects around 48 million people worldwide. It is less common than other types of hepatitis that you might be more familiar with.

The disease, which is caused by the hepatitis D virus (HDV), differs from other forms of viral hepatitis. It can only cause disease in people who are infected with the hepatitis B virus (HBV) because HDV cannot replicate without HBV being present.

Hepatitis D Chronic Stage Symptoms

Verywell / Jessica Olah

Hepatitis D is thought to be uncommon in the United States. It is mostly seen in developing natons where hepatitis B is widespread.

Even though it is uncommon, HDV is considered to be the most severe form of viral hepatitis and comes with a high risk of complications, including cirrhosis, liver failure, and liver cancer.

Hepatitis D is associated with the rapid progression of liver disease in chronically infected people and has a mortality rate of around 20%—higher than any other form of viral hepatitis.

Types

As with other forms of viral hepatitis, hepatitis D can cause an acute (short-term) infection that often resolves on its own without any problems. However, in some people, the infection can persist and become chronic (long term), causing progressive injury to the liver.

How and when you get hepatitis D can make a big difference in the course of the infection. There are two different ways that a person can get the virus.

  • HBV/HDV coinfection: When a person is simultaneously infected with HBV and HDV
  • HDV superinfection: When a person who is chronically infected with HBV is later infected with HDV

The differences might not sound extreme, but a superinfection is considered to be a far more serious condition. Around 80% of superinfected people will go on to develop a chronic infection compared to only 5% of coinfected individuals.

HDV superinfection is also associated with the rapid progression of liver disease. In those who are chronically infected, between 70% and 80% will develop cirrhosis and liver failure within five to 10 years, while 15% will experience the same within one to two years.

This is double the rate seen in people chronically infected with HBV on its own.

Genotypes

HDV can also be categorized by its genetic characteristics (genotype). There are three HDV genotypes that vary by their geographic location and disease pattern (pathogenesis).

  • Genotype 1: The predominant type found in Western countries, this type is characterized by rapid disease progression and an increased risk of liver failure.
  • Genotype 2: Found mainly in Asia, this type tends to progress slowly and is less likely to cause a chronic infection.
  • Genotype 3: The predominant type in South America, this type often causes severe acute symptoms and the rapid progression to liver failure.

Symptoms

The symptoms of hepatitis D vary by the stage of the infection: acute or chronic. The acute stage develops soon after the infection is established and can last for several weeks or months. The chronic phase can persist for years and even decades.

Acute Stage

As with other forms of viral hepatitis, the majority of people infected with HDV will experience no obvious signs and symptoms during the acute phase. If the immune system is able to clear the infection, people may not even know that they've been infected.

If symptoms do develop, they are difficult to tell apart from those of other forms of viral hepatitis. The most common symptoms are:

  • Fatigue
  • Nausea
  • Fever
  • Malaise (a general feeling of unwellness)
  • Upper-right abdominal tenderness and pain (where the liver is located)
  • Jaundice (yellowing of the skin and/or eyes)
  • Choluria (dark urine)
  • Clay-colored stool

Acute symptoms tend to resolve within two to four weeks, although it may take longer for jaundice to fully disappear.

In rare cases, an acute HDV infection can lead to fulminant hepatitis, a potentially life-threatening condition that causes liver tissue death (necrosis) and acute liver failure. Symptoms of this complication include jaundice, vomiting, abdominal swelling, confusion, tremors, and a fruity breath smell.

Fulminant hepatitis involves extreme liver function failure. It occurs in less than 1% of all acute HBV infections. When HDV is involved, the risk can jump to as much as twentyfold.

Chronic Stage

Chronic hepatitis D occurs when the immune system is unable to clear the virus. Once the acute symptoms have resolved, the infection can remain "silent" for years and even decades, causing progressive injury to the liver even if a person is not aware of it.

The first signs of chronic hepatitis are often associated with the onset of cirrhosis, a condition in which the buildup of scar tissues impairs the function of the liver.

The symptoms are progressive and may include:

Cirrhosis is said to be "compensated" when the liver is damaged but still relatively functional. When it is "decompensated," the liver is no longer functional.

With hepatitis D, the risk of decompensated cirrhosis and liver failure is greater than with any other form of viral hepatitis—especially in people with HDV superinfection.

In addition to cirrhosis, people with chronic hepatitis D are also at a two-fold greater risk of developing liver cancer than people with HBV alone.

Causes

The hepatitis D virus, also known as the delta virus, is unique in that it cannot replicate on its own. It is considered a "satellite virus" because it needs HBV to complete its life cycle and make copies of itself.

In most cases, HDV is the dominant virus in the infection. As it suppresses HBV to low levels, it utilizes HBV's surface proteins to assemble new copies of itself. Any liver damage that occurs, therefore, is the result of hepatitis D rather than hepatitis B.

Hepatitis D is mainly spread through blood exposure. Shared needles and syringes are among the most common causes. In developing nations where HDV is endemic, unsterile medical devices, contaminated blood or clotting factor, and shared personal care items (like barbershop razors) are also sources of infection.

The sexual transmission of HDV is uncommon but can occur. HDV transmission from mother to child during childbirth, while possible, is thought to be rare.

Hepatitis D is not spread through contaminated food or water, shared utensils, breastfeeding, kissing, coughing, or sneezing.

HDV is most common in East Africa, central and northern regions of Asia, the Amazon Basin, the Middle East, and certain areas of the Pacific.

Diagnosis

Arguably the biggest challenge in diagnosing hepatitis D is recognizing the signs of infection. Hepatitis D is uncommon in the United States, so it can sometimes be overlooked in a patient—particularly in cases of HBV/HDV coinfection.

By contrast, HDV superinfection is often recognized by the sudden worsening of symptoms in people previously diagnosed with HBV.

While there can be many causes for the rebound of hepatitis symptoms, certain clues suggest that HDV is involved (such as travel to an endemic region or injection drug use).

HDV Screening Recommendations

The American Association for the Study of Liver Disease (AASLD) currently recommends HDV screening for anyone with hepatitis B who is at high risk for hepatitis D, including injecting drug users, people with HIV, men who have sex with men, and people arriving from countries where HDV is endemic.

If HDV is suspected, it can be diagnosed using a series of simple blood tests.

Total Antibody Test

An HDV total antibody test is used to detect different antibodies (immunoglobulins) that are produced by the body at different stages of infection. This includes immunoglobulin M (IgM) produced during early-stage infection and immunogilobulin G (IgG) produced when IgM levels start to decrease.

Based on which antibodies are elevated, the test can not only confirm that an infection is present but also establish the pattern of infection. The IgM/IgG pattern can help determine if the infection is acute or chronic, or if a coinfection or superinfection is involved.

PCR Qualitative Tests

Tests known as PCR qualitative tests are typically performed if a total antibody test is positive. Rather than looking at the "footprint" of the infection (that is, antibodies), this test looks at the virus itself using a technology called polymerase chain reaction (PCR) that detects viral RNA.

The PCR test can both confirm the diagnosis and indicate if the infection is active. Factors like this can help direct the appropriate course of treatment.

Other Tests and Procedures

Once hepatitis D is diagnosed, other tests are performed on a routine basis to monitor the disease's progression and a person's response to treatment.

  • Liver function tests (LFTs): A panel of blood tests that indicates the status of the liver based on enzymes produced in response to liver injury
  • Platelet count: A blood test that is used to detect changes in blood consistent with portal hypertension (a complication of cirrhosis)
  • Fibroscan: A specialized form of ultrasound that can measure and monitor liver scarring (fibrosis)
  • Fibrosis-4 (FIB-4) Index: A scoring system based on a person's age and lab results that can estimate the degree of liver impairment and the stage of fibrosis
  • HDV viral load: A blood test (also known as the quantitative HDV PCR) that measures the amount of virus in a sample of blood

Given the availability of noninvasive tests, a liver biopsy is less commonly used for disease staging. However, if the diagnosis is unclear or if a co-occurring condition such as nonalcoholic fatty liver disease (NAFLD) or alcohol-associated liver disease (AALD) is involved, it might be used.

Treatment

Unlike hepatitis B, there are no recommended treatments for hepatitis D. That does not mean that hepatitis D is treated in the same way as hepatitis B.

Clinical guidelines for treating hepatitis B

Treatment guidelines for STIs, updated by the U.S. Centers for Disease Control and Prevention in 2021, note that there is no specific treatment available for people experiencing acute hepatitis B. People with chronic hepatitis B should see a specialist experienced in managing such infections and take medications to help suppress replication and work toward remission of liver disease.

HDV will be the dominant virus in most cases; therefore, the treatment will be focused on conventional therapies that help reduce the HDV viral load and slow disease progression. A viral load is the amount of the virus in a person's body.

Antiviral drugs that are commonly used to treat HBV, like Viread (tenofovir) and Baraclude (entecavir), generally have little effect on HDV. However, they might be used on an experimental basis in combination therapies.

Pegylated Interferon-Alpha

Pegylated interferon-alpha (INF-a), a drug used for the treatment of hepatitis B and hepatitis C since the early 2000s, is typically used as the first-line (initial) treatment of hepatitis D.

The medication is delivered by an under-the-skin (subcutaneous) injection once weekly for at least a year to reduce the amount of HDV in the blood. The injections can be given at home using a traditional syringe and vial or a pen-like autoinjector.

Studies have shown that pegylated INF-a helps one in four people with chronic HDV achieve a sustained undetectable viral load within six months. However, the viral load will typically rebound once the treatment is stopped.

Pegylated INF-a is also known to cause significant toxicity with ongoing use. Common side effects include:

  • Cough
  • Sore throat
  • Fevers and chills
  • Flushing
  • Loss of appetite
  • Changes in taste
  • Nausea
  • Depression
  • Irritability
  • Lethargy
  • Trouble sleeping
  • Unusual bruising or bleeding
  • Ulcers, sores, or plaques in the mouth
  • Diarrhea
  • Constipation
  • Difficulty urinating or painful urination
  • Black tarry stools

The long-term use of pegylated INF-a can also increase the risk of diabetes, thyroid disease, kidney dysfunction, seizures, and certain autoimmune diseases.

Other Treatments

A few experimental drugs have shown promise in the treatment of HDV. Among some of the leading candidates are:

  • Hepcludex (bulevirtide) is an oral drug that prevents HDV from entering liver cells. Early studies have shown that Hepcludex is tolerable and can reduce the viral load to undetectable levels in some people. Hepcludex was approved for use by the European Union in 2020.
  • Zokinvy (lonafarnib) is an oral drug that prevents HBV replication by blocking the enzymes that are needed to assemble new viruses. When used in combination with pegylated INF-a and an antiviral called ritonavir, Zokinvy can reduce the HDV viral load and normalize liver enzymes in some people.

Liver Transplant

The only viable treatment for people with decompensated cirrhosis is a liver transplant. Following the transplant, a combination of intravenous anti-HBV immunoglobulins and oral antivirals can help prevent the re-emergence of hepatitis B. Without HBV to facilitate replication, HDV is far less likely to recur.

A 2019 study published in Transplant Proceedings found that only 14% of people who underwent a liver transplant for HDV experienced recurrence.

Prevention

The best way to prevent hepatitis D is to prevent hepatitis B. By getting vaccinated with one of three approved hepatitis B vaccines—Engerix-B, Recombivax HB, or Heplisav B—you can prevent HDV from causing harm if you do get infected.

Although HDV can enter cells on its own, it cannot replicate without HBV. Without the means to rapidly grow, HDV cannot cause disease.

Infants are typically vaccinated soon after birth and complete the vaccine series by six months of age. Children and adults who have not been vaccinated can also receive the HBV vaccine in two or three doses, depending on their age and the vaccine type.

Coping

Although hepatitis D can be treated, it cannot be cured. A person will need to take care of their liver by making changes to their diet and lifestyle, such as:

  • Avoiding alcohol: Alcohol not only damages liver cells but also causes fat to build up in the liver, leading to hepatic steatosis (fatty liver disease).
  • Stopping cigarettes: Cigarette smoke can aggravate already inflamed liver tissues and potentially increase the risk of liver cancer.
  • Limiting saturated fats and sugar: The overconsumption of refined sugar and saturated fat can also increase the risk of hepatic steatosis and promote the development of cirrhosis.
  • Avoiding raw shellfish: Raw shellfish may be contaminated with bacteria called Vibrio vulnificus, which is extremely toxic to the liver.
  • Eating a nutritious diet. Eat plenty of fresh fruits, vegetables, whole grains, fish, and lean meats. Some studies suggest that cruciferous vegetables like broccoli and cabbage may protect the liver from environmental toxins.
  • Avoiding certain medications: Some common drugs like Tylenol (acetaminophen), Dilantin (phenytoin), methotrexate, and Augmentin (amoxicillin/clavulanate) can be harmful to the liver. Let your doctor know about any drugs you take (including herbal remedies) to avoid injury.
  • Getting the hepatitis A vaccine: Hepatitis A vaccination can prevent further harm to your liver, providing protection against this common form of viral hepatitis for up to 25 years.

A Word From Verywell

It can be distressing to learn that you have hepatitis D. Coming to terms with the diagnosis may take time, but with education and support, you can learn how you manage your condition and protect your liver from avoidable harm.

Being under the care of a qualified gastroenterologist or hepatologist is key to maintaining your health. By seeing your doctor regularly and monitoring the status of your liver, your doctor can act quickly if complications arise and even detect problems before they occur.

If current treatments do not work for you, you may wish to learn about developing research and explore clinical trials. As scientists learn more about hepatitis D, the hope is that a breakthrough like the one seen with hepatitis C—a disease considered incurable just 20 years ago—could be on the horizon.

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