Hepatitis D: A Deeper Look at the Most Severe Viral Hepatitis
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Hepatitis D, also called HDV infection, is widely known as the toughest form of viral hepatitis. Although not as famous as some other liver diseases, its impact can be devastating for those who get infected. The big twist with hepatitis D is that it depends on another virus—hepatitis B—to survive and multiply. In other words, you need to be infected with hepatitis B virus (HBV) first, or at the same time, for HDV to become active [1, 7]. This can happen when someone catches both HBV and HDV at once (coinfection), or when HDV strikes later if a person is already living with chronic HBV (superinfection).
Table of Contents
- Understanding Hepatitis D Disease
- The Global Impact
- Clinical Features
- Diagnosing Hepatitis Delta Virus
- Treatment Options
- Prevention of Hepatitis D with Hepatitis B Vaccine
- Closing Thoughts
- References
Understanding Hepatitis D Disease
Structure and Replication
HDV is an unusual type of virus, sometimes referred to as a defective RNA viroid. By itself, it can’t do much. It actually relies on the hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) to make new copies. Because of this special arrangement, HDV gets passed along the same routes as HBV, mainly through contact with infected blood—like sharing contaminated needles or receiving tainted blood products [4, 8]. Vaccination against hepatitis B virus (HBV) is crucial as it effectively prevents hepatitis D infection by eliminating the necessary environment for HDV replication.
HDV Genotypes
Scientists have found eight genotypes, or strains, of HDV. Different genotypes are common in different places. Some of these strains can lead to worse complications, including faster liver damage, while others seem milder. But no matter which genotype a person has, any form of HDV infection can cause more harm to the liver than HBV alone ([2]).
The Global Impact
Hepatitis D exists worldwide but tends to show up more often in specific groups. The hepatitis delta virus (HDV) is transmitted primarily through contact with infected blood, similar to hepatitis B virus (HBV). People who inject drugs face a high risk, partly because of needle sharing. Additionally, folks who come from regions where hepatitis D is widespread might bring the virus with them, possibly spreading it to new locations. Figuring out exactly how many people have HDV can be tricky. Some studies rely on small groups, others use different tests, and that causes confusion about the true numbers [6]. However, experts estimate it may range anywhere from 12 to 72 million people globally.
Clinical Features
Patterns of Infection
- Coinfection: When a person catches HBV and HDV at the same time. This often triggers a serious acute illness but may go away after the immune system clears both viruses. Acute hepatitis D can present with severe symptoms and may lead to acute liver failure, especially in coinfections.
- Superinfection: When HDV infects someone who already has long-term (chronic) hepatitis B. In this scenario, HDV hits harder, and the chances of rapid liver deterioration go up significantly [10].
Disease Progression
Compared to an HBV infection by itself, HDV can cause:
- Higher risk of lasting liver damage
- Faster scarring (fibrosis)
- Quicker path to cirrhosis (severe scarring)
- Greater odds of developing hepatocellular carcinoma (HCC), a type of liver cancer [2, 3]
Chronic infections with HDV significantly increase the risk of liver failure, cirrhosis, and liver cancer.
Because HDV often speeds up these serious complications, people who have both HBV and HDV need to keep a close eye on their health to catch any warning signs early.
Diagnosing Hepatitis Delta Virus
Spotting HDV can be complicated. One reason is that many labs worldwide don’t always have the specialized tests to detect it. Plus, in the early stages of infection, HDV might not appear in standard bloodwork. All of this makes it tough to get a quick diagnosis. Despite these hurdles, it’s vital to find HDV as soon as possible, since proper diagnosis can help prevent severe liver problems later [7]. Early detection of chronic infections is crucial to prevent severe liver complications and improve patient outcomes.
Treatment Options
Current Treatments
Doctors have used pegylated interferon-α (IFN-α) for a while to tackle HDV, but it doesn’t always work well. Many patients deal with relapses after treatment, and side effects can be rough [5]. Effective management of chronic infection with HDV is essential to reduce the risk of severe liver disease and improve long-term health outcomes.
Emerging Therapies
Several new therapies are under study and, though still in development, they bring hope for people battling chronic HDV:
- Bulevirtide: A breakthrough therapy specifically designed for HDV.
- Interferon lambda: Aims for a targeted immune response that might cause fewer unwanted side effects.
- Lonafarnib: Works by interfering with how the virus assembles itself.
- Nucleic acidic polymers: Tested for their ability to stop HDV from entering cells and replicating [3, 7].
These medications could transform how we care for people infected with hepatitis D, offering better outcomes and fewer complications.
Prevention of Hepatitis D with Hepatitis B Vaccine
Because HDV relies on HBV, stopping the spread of HBV and preventing hepatitis B infection in the first place is the best way to guard against HDV. Some core prevention steps include:
- HBV Vaccination: Getting vaccinated against hepatitis B drastically lowers the chance of HDV infection [1]. Encouraging widespread use of the hepatitis B vaccine is a critical step in preventing hepatitis B infection and, consequently, hepatitis D infection.
- Safe Injection Practices: Ensuring all medical and non-medical injections (like tattooing or piercing) are done with sterile equipment.
- Screening Blood Products: Regular testing makes sure that blood donors aren’t carrying HBV or HDV, preventing new infections.
Closing Thoughts
Hepatitis D is often called the toughest type of viral hepatitis for good reason. The complications of hepatitis D, including severe liver diseases and liver failure, underscore the need for early diagnosis and effective treatment. It makes hepatitis B more severe and can rapidly push the liver toward dangerous complications. Yet, thanks to ongoing research, there are more solutions today than ever before. Groundbreaking therapies, improved understanding of the virus, and broader vaccination programs offer new ways to beat HDV.
Still, major hurdles remain. It’s important to encourage wider access to HBV vaccination and better testing to catch HDV sooner. Ongoing studies on therapies like bulevirtide and lonafarnib could pave the way for safer and more effective treatment strategies. By raising global awareness and combining prevention with medical innovation, we stand a real chance of halting the harmful effects of HDV once and for all.
References
[1] Menegale, F., Manica, M., Zardini, A., Guzzetta, G., Marziano, V., d’Andrea, V., Trentini, F., Ajelli, M., Poletti, P., & Merler, S. (2023). Evaluation of Waning of SARS-CoV-2 Vaccine-Induced Immunity: A Systematic Review and Meta-analysis. JAMA network open, 6(5), e2310650. https://doi.org/10.1001/jamanetworkopen.2023.10650
[2] Wedemeyer, H., & Manns, M. P. (2010). Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nature reviews. Gastroenterology & hepatology, 7(1), 31–40. https://doi.org/10.1038/nrgastro.2009.205
[3] Yardeni, D., Heller, T., & Koh, C. (2022). Chronic hepatitis D-What is changing?. Journal of viral hepatitis, 29(4), 240–251. https://doi.org/10.1111/jvh.13651
[4] Rizzetto M. (2015). Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harbor perspectives in medicine, 5(7), a021576. https://doi.org/10.1101/cshperspect.a021576
[5] Da, B. L., Heller, T., & Koh, C. (2019). Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterology report, 7(4), 231–245. https://doi.org/10.1093/gastro/goz023
[6] Post, Z., & Reau, N. (2023). What Is the Real Epidemiology of Hepatitis D Virus and Why so Many Mixed Messages?. Clinics in liver disease, 27(4), 973–984. https://doi.org/10.1016/j.cld.2023.05.011
[7] Lampertico, P., Degasperi, E., Sandmann, L., Wedemeyer, H., & Delta Cure 2022 Working Group (2023). Hepatitis D virus infection: Pathophysiology, epidemiology and treatment. Report from the first international delta cure meeting 2022. JHEP reports : innovation in hepatology, 5(9), 100818. https://doi.org/10.1016/j.jhepr.2023.100818
[8] Pascarella, S., & Negro, F. (2011). Hepatitis D virus: an update. Liver international : official journal of the International Association for the Study of the Liver, 31(1), 7–21. https://doi.org/10.1111/j.1478-3231.2010.02320.x
[9] Mentha, N., Clément, S., Negro, F., & Alfaiate, D. (2019). A review on hepatitis D: From virology to new therapies. Journal of advanced research, 17, 3–15. https://doi.org/10.1016/j.jare.2019.03.009
[10] Farci, P., & Niro, G. A. (2012). Clinical features of hepatitis D. Seminars in liver disease, 32(3), 228–236. https://doi.org/10.1055/s-0032-1323628
