Hepatitis B, hepatitis E, and hepatitis D are all viral infections that affect the liver; however, they have different causative viruses and modes of transmission. Hepatitis B is primarily transmitted through contact with infected bodily fluids or blood, while hepatitis E is typically transmitted through contaminated food or water.
Hepatitis D is a viral infection caused by the hepatitis delta virus (HDV), which can only infect people who are already infected with the hepatitis B virus (HBV), and sometimes those who have the human immunodeficiency virus (HIV). Hepatitis D is a serious disease that can cause liver damage, liver failure, cirrhosis (scarring), and liver cancer.
It is estimated that around 20 million people are infected with the hepatitis D virus worldwide. Individuals already infected with HBV are the most vulnerable to HDV infection, particularly those who use injections or engage in unprotected sexual activity with multiple partners.
Despite its prevalence, hepatitis D remains a poorly understood disease with limited treatment options. This article aims to shed light on the hepatitis D virus, its prevention, treatment, and management.
Hepatitis D, HDV, or delta hepatitis is a liver disease that requires the presence of the hepatitis B virus (HBV) to replicate and cause infection.1 This means that people already infected with the hepatitis B virus and tested positive for the hepatitis B surface antigen (HBsAg) are at risk of contracting hepatitis D. Around 5% of people infected with HBV also have HDV.2
Hepatitis D has its highest prevalence in the Mediterranean area, Eastern Europe, East Africa, the Amazon basin, the Middle East, Central and Northern Asia, and certain areas of the Pacific. Being the most severe form of the hepatitis virus, it not only causes severe liver damage but even death if left untreated.1,3,4
Hepatitis D can occur in two ways:
- Co-infection occurs when a person is infected with both the hepatitis B virus and hepatitis D virus. Co-infection usually results in more severe acute disease than HBV alone but rarely leads to chronic infection
- Superinfection occurs when a person with a chronic hepatitis B infection becomes infected with the hepatitis D virus. Superinfection can lead to severe and often rapidly progressive liver disease
HDV infection can cause acute or chronic hepatitis. Acute hepatitis D is a short-term illness that typically resolves independently within a few weeks. Chronic hepatitis D, on the other hand, causes serious liver damage, such as cirrhosis and liver cancer. The severity of the disease depends on various factors, including the presence of other underlying liver diseases, the age of the patient, and the HDV genotype.3
Causes of hepatitis D
Hepatitis D is caused by the hepatitis D virus (HDV), a small, spherical, enveloped RNA virus. HDV can only multiply in the presence of hepatitis B virus (HBV), which means that people infected with HBV can also be infected with HDV. Hepatitis D can also be a superinfection in people infected with HIV.
The exact mechanism by which HDV replicates in the presence of HBV is not fully understood but is thought to be related to how HDV uses the HBV surface antigen (HBsAg) to infect liver cells. HDV requires HBsAg to form a protective envelope around the virus particle, allowing it to enter liver cells and initiate infection.
The primary mode of transmission for hepatitis D is through contact with contaminated blood or body fluids, like other blood-borne pathogens. Transmission can happen in one of the following ways:
- Injections, needlestick injuries, or transfusion of contaminated blood products
- Sharing personal items like toothbrushes and razors that may have been infected with the blood of an infected person
- Sexual transmission of hepatitis D is also possible, especially between people who engage in high-risk sexual behaviours or have multiple sexual partners
- Mother-to-child transmission of HDV, although relatively rare, can occur during childbirth if the mother is co-infected with HBV and HDV
Signs and symptoms of hepatitis D
The severity of symptoms varies in individuals and the stage of the disease. Sometimes, people with hepatitis D may be asymptomatic, having no symptoms. Some signs and symptoms associated with hepatitis D, which are similar to those of other types of hepatitis, include:
- Jaundice, a condition identified by the yellowing of the skin and whites of the eyes, is caused by the impact of HDV on the liver, leading to excessive production of bilirubin. This is a chemical compound produced by the liver that has several functions, including digesting food
- Abdominal pain, especially around the upper right part of the tummy, under the lower ribs. This is where the liver is located
- Tiredness is caused by changes in how the brain communicates with the affected liver
Other symptoms that may signify a hepatitis D infection include:
- Loss of appetite
- Nausea and vomiting
- Dark urine
- Black stools
- Joint pain
It is important to understand that having one or more of these does not automatically translate to hepatitis D infection, as other factors unrelated to the hepatitis D virus may trigger these symptoms. Only your healthcare provider can determine the root cause of your symptoms and the appropriate treatment plan you need.
Management and treatment for hepatitis D
It is important to get tested if you have come in contact with the hepatitis D virus, such as through contact with infected blood or bodily fluids, or if you are at a high risk of infection due to other factors, such as injection drug use. A doctor can perform blood tests to check for the presence of the virus and determine if you need treatment.
The treatment of chronic hepatitis D has remained an unmet medical need. Hepatitis D treatment typically involves symptom management, preventing complications, and supporting liver function. Professional societies have only approved pegylated interferon (Peg-IFN), which has limited efficacy. The treatment could span one year and aims to prevent HDV replication, as indicated by the resulting lack of HDV RNA in serum and hepatitis D antigen (HDAg) in the liver.1,5
Antiviral medications may sometimes be prescribed to inhibit virus replication and reduce liver inflammation. Your doctor can work with you to outline a treatment plan for your specific needs. In extreme cases, liver transplantation may be required.
Scientists are currently studying the structure and behaviour (assembly) of the HDV virus using specialised microscopy techniques to visualise the virus at the molecular level. This study has been instrumental in advancing our understanding of HDV and its interactions with the host cell. It will also be used to develop new treatments for the disease.3,6
Prevention is crucial in controlling the spread of the hepatitis D virus. No specific vaccine prevents hepatitis D. However, vaccination against hepatitis B can help prevent HDV infection in people not already infected. Treatment options for hepatitis D are also limited, with interferon therapy being the only approved treatment. However, new treatments, including drugs targeting the HDV molecular assembly, are currently under development.5
How is hepatitis D diagnosed?
Hepatitis D is diagnosed through a series of tests that detect the presence of the hepatitis D virus (HDV) in the blood and evaluate liver function. It is important to note that hepatitis D diagnosis can be difficult because the symptoms and test results can be similar to other liver diseases, such as hepatitis B or C.
How can I prevent hepatitis D?
Hepatitis D is a serious public health concern, particularly in areas where it is more common. Measures to control the spread of the disease include vaccination against hepatitis B, which can help prevent HDV infection in people who are not already infected. Other strategies include blood screening to prevent the transmission of the virus through blood transfusions and the promotion of safe injection practices.
Who is at risk of hepatitis D?
People already infected with the hepatitis B virus or HIV are at risk of being infected by the hepatitis D virus, as well as people who are exposed to the virus through contact with an infected person.
How common is hepatitis D?
The hepatitis D virus infects up to 15-20 million people worldwide. However, this may be underestimated due to the difficulty in diagnosing the disease and the need for more surveillance programs in some regions. Hepatitis D virus is more common in areas where the hepatitis B virus is prevalent, such as parts of Asia, Africa, and South America.
Is hepatitis D contagious?
Hepatitis D is contagious and can be transmitted through various routes, including unprotected sexual intercourse, sharing needles, and mother-to-child transmission.
When should I see a doctor?
If you suspect you may have hepatitis D or have symptoms like fatigue, fever, abdominal pain, nausea, vomiting, loss of appetite, and jaundice, seeing a doctor as soon as possible is important.
Hepatitis D is a viral liver disease caused by the hepatitis D virus, which infects people who have already contracted the hepatitis B virus. The hepatitis B virus allows the hepatitis D virus to replicate and cause infection in most cases. Hepatitis D virus is typically spread through contact with infected blood or other bodily fluids, sharing of needles, or transmitted from mother to child during childbirth, and is more common in endemic regions.
Jaundice, fatigue, abdominal pain, and loss of appetite are some symptoms of the hepatitis D virus. Although there is no specific treatment for hepatitis D available at the moment, managing symptoms and preventing complications is important to avoid or delay further complications. Vaccination against hepatitis B, practising safe sex, and avoiding sharing needles or injection equipment are preventative measures and are key to controlling the spread of hepatitis D.
Symptoms of hepatitis D may mimic other liver diseases. As such, it is crucial to see your doctor once you suspect you have been exposed to or have the hepatitis D virus or are at risk of contracting it due to an underlying infection or health condition.
- Masood U, John S. Hepatitis D. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470436/
- Urban, Stephan, et al. “Hepatitis D Virus in 2021: Virology, Immunology and New Treatment Approaches for a Difficult-to-Treat Disease.” Gut, vol. 70, no. 9, Sept. 2021, pp. 1782–94. DOI.org (Crossref).Available from: https://doi.org/10.1136/gutjnl-2020-323888
- Mentha, Nathalie, et al. “A Review on Hepatitis D: From Virology to New Therapies.” Journal of Advanced Research, vol. 17, May 2019, pp. 3–15. DOI.org (Crossref). Available from: https://doi.org/10.1016/j.jare.2019.03.009
- Da, Ben L., et al. “Hepatitis D Infection: From Initial Discovery to Current Investigational Therapies.” Gastroenterology Report, vol. 7, no. 4, Aug. 2019, pp. 231–45. DOI.org (Crossref), https://doi.org/10.1093/gastro/goz023
- Caviglia, Gian Paolo, et al. “A Review of HDV Infection.” Viruses, vol. 14, no. 8, Aug. 2022, p. 1749. DOI.org (Crossref). Available from: https://doi.org/10.3390/v14081749.
- Lempp, Florian, and Stephan Urban. “Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen.” Viruses, vol. 9, no. 7, July 2017, p. 172. DOI.org (Crossref). Available from: https://doi.org/10.3390/v9070172