Hepatitis D

Hepatitis D, also known as Hepatitis delta, is a type of viral hepatitis caused by the Hepatitis delta virus (HDV). HDV is unique because it can only propagate in the presence of the hepatitis B virus (HBV).

There are two modes of transmission: simultaneous infection with HBV (coinfection) or superinfection in individuals with chronic hepatitis B.

Virology

Hepatitis delta virus (HDV) is a small, spherical, enveloped particle with a 36 nm diameter. Its viral envelope contains host phospholipids and three proteins from the hepatitis B virus: the large, medium, and small hepatitis B surface antigens.

Inside, the genome is a single-stranded, closed circular RNA surrounded by the hepatitis D antigen (HDAg).

Figure 1: Schematic representation of the Hepatitis delta virus virion

Signs and Symptoms

Patients infected with HDV typically experience symptoms such as fatigue, nausea, and vomiting. The infection can lead to severe complications including liver cirrhosis and an increased risk of liver cancer.

When HDV infects someone with chronic hepatitis B (superinfection), it is considered the most severe form of viral hepatitis due to the high likelihood of liver failure and rapid progression to cirrhosis.

Transmission

HDV is transmitted through parenteral routes similar to HBV, including:

• Intravenous drug use
• Receiving clotting factor concentrates
• Blood transfusions with contaminated blood

Individuals with hepatitis B are at increased risk of HDV infection. HDV is rare in developed countries but prevalent in the Mediterranean region, sub-Saharan Africa, the Middle East, and South America.

Diagnosis

Diagnosis of hepatitis D involves testing for anti-HDV antibodies, indicating past or present infection. Active HDV infection is confirmed by measuring hepatitis D RNA levels.

Testing is only recommended for those who are hepatitis B surface antigen positive since HDV requires HBV to replicate.

Prevention

Vaccination against hepatitis B effectively prevents HDV infection, as HDV cannot infect individuals without HBV. The World Health Organisation recommends universal vaccination against hepatitis B, usually administered within 24 hours of birth.

Using latex or polyurethane condoms and sterile equipment for tattoos and body piercings can also prevent transmission.

Treatment

Established treatments for chronic hepatitis D include antiviral medications like pegylated interferon alpha and the antiviral drug bulevirtide, which blocks HDV from entering hepatocytes. However, treatment is only effective while the drug is administered, with benefits ceasing upon discontinuation.

New treatments under development include pegylated interferon lambda and the prenylation inhibitor lonafarnib.

Prognosis

Superinfection with HDV in chronic hepatitis B patients leads to a poorer prognosis compared to coinfection. Chronic HDV infection is associated with a high risk of developing liver cirrhosis and cancer, with 75% of patients developing cirrhosis within 15 years.

The most significant risk factor for disease progression is persistent HDV viraemia.

Epidemiology

HDV is prevalent worldwide, with an estimated 48 million people infected. The prevalence is higher in regions with high HBV infection rates, such as the Amazon basin, Asia, and Africa.

Vaccination programmes have reduced HDV prevalence in higher-income countries, though rates remain high among intravenous drug users and immigrants from HDV endemic regions.

Figure 2: Worldwide prevalence of HDV among HBV carriers in 2015

History

Hepatitis D was first reported in 1977 and initially thought to be part of HBV. It was later identified as a distinct virus requiring HBV for replication.

The complete genome was sequenced in 1986, and HDV was classified into its genus, Deltavirus.

Lábrea fever, a lethal tropical infection, is a coinfection or superinfection of hepatitis B with hepatitis D, prevalent in the Brazilian Amazon basin.

Figure 3: Nobel Prize in Physiology or Medicine 2020: Seminal experiments leading to the discovery of HCV as the causative agent of non-A, non-B hepatitis

Self-assessment MCQs (single best answer)

Hepatitis D requires the presence of which other virus to propagate?

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What is the most severe complication associated with Hepatitis D superinfection in individuals with chronic Hepatitis B?

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Which method is primarily used to diagnose active Hepatitis D infection?

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Which of the following is an effective measure to prevent Hepatitis D infection?

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Which antiviral drug was approved by the European Medicines Agency in 2020 for the treatment of Hepatitis D?

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What is the typical incubation period for Hepatitis D?

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Which of the following regions has the highest prevalence of Hepatitis D?

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What is the structure of the Hepatitis D virus genome?

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Which of the following is a significant risk factor for Hepatitis D infection?

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Which of the following genotypes of Hepatitis D is associated with severe hepatitis in South America?

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