Hepatitis D: Transmission, Symptoms, Diagnosis, Treatment and Prevention

The most common cause of hepatitis is infection with a virus. There are five different viruses which can cause five different types of viral hepatitis viz Hepatitis A virus (HAV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus (HDV) and Hepatitis E virus (HEV). Hepatitis D is spread in the same way as hepatitis B and hepatitis C; however, it can only affect people who also have been infected with hepatitis B. This article is about the HDV infection.

In this article:
What is hepatitis D?
How common is hepatitis D?
How is hepatitis D transmitted? And who is most at risk?
What are the symptoms of hepatitis D?
Screening and diagnosis of hepatitis D
Treatment of hepatitis D
Prevention of hepatitis D

What is hepatitis D?

Hepatitis D, also known as “delta hepatitis,” is a liver disease in both acute (short term) and chronic (persistent) forms caused by the hepatitis D virus (HDV) that requires HBV for its replication (survival by multiplication). Hepatitis D infection cannot occur in the absence of hepatitis B virus. HDV infection occurs only simultaneously or as super-infection with HBV. HDV-HBV co-infection is considered the most severe form of chronic viral hepatitis due to more rapid progression towards liver-related death and hepatocellular carcinoma (liver cancer). See the separate article, Hepatitis B: Risk Factors, Symptoms, Diagnosis, Prevention and Treatment, for more details.

A vaccine against hepatitis B is the only method to prevent HDV infection.

Diagram showing abdominal organs, including the liver

How common is hepatitis D?

In a study published in the Journal of Hepatology in 2020 that was conducted in collaboration with the World Health Organization (WHO), it was estimated that hepatitis D virus (HDV) affects globally nearly 5% of people who have a chronic infection with hepatitis B virus (HBV) and that HDV co-infection could explain about 1 in 5 cases of liver disease and liver cancer in people with HBV infection. The study has identified several geographical hotspots of high prevalence of HDV infection, including Mongolia, the Republic of Moldova, and countries in Western and Middle Africa.

How is hepatitis D transmitted?

The routes of HDV transmission are the same as for HBV: percutaneously (through the skin and mucuous membrane) or sexually through contact with infected blood or blood products or other bodily fluids. See the separate article, What Is Blood?, for more on blood. Vertical transmission (from mother to child during birth and delivery) is possible but rare. Vaccination against HBV prevents HDV coinfection, and hence expansion of childhood HBV immunization programmes has resulted in a decline in hepatitis D incidence worldwide.

Who is at risk?

Chronic HBV carriers are at risk for infection with HDV.

People who are not immune to HBV (either by natural disease or immunization with the hepatitis B vaccine) are at risk of infection with HBV which puts them at risk of HDV infection.

Those who are more likely to have HBV and HDV co-infection include people who inject drugs, indigenous people and people with hepatitis C virus or HIV infection. The risk of co-infection also appears to be potentially higher in recipients of hemodialysis, men who have sex with men and commercial sex workers.

Migration from high HDV prevalence countries to lower prevalence areas might have an effect on the epidemiology of the host country.

See the separate articles, Hepatitis B: Risk Factors, Symptoms, Diagnosis, Prevention and Treatment, and also Hepatitis C: Causes, Symptoms, Diagnosis, Treatment and Prevention, and also HIV Disease: Causes, Symptoms, Treatment and Key Facts, for more details.

What are the symptoms of hepatitis D?

It is helpful to think of two forms of infection with the hepatitis D germ (virus).

• A short-term (acute) form when you are first infected; and
• A superinfection form when the HDV virus comes on top of previous HBV infection.

Acute hepatitis

Simultaneous infection with HBV and HDV can lead to a mild-to-severe or even fulminant (sudden in onset and life-threateningly severe) hepatitis, but recovery is usually complete and development of chronic hepatitis D is rare (less than 5% of acute hepatitis).

Superinfection

HDV can infect a person already chronically (persistently) infected with HBV. The superinfection of HDV on chronic hepatitis B accelerates progression to a more severe disease in all ages and in 70‒90% of persons. HDV superinfection accelerates progression to liver cirrhosis (irreversible scarring through fibrosis of the liver) almost a decade earlier than HBV mono-infected persons, although HDV suppresses HBV replication. The mechanism in which HDV causes more severe hepatitis and a faster progression of fibrosis than HBV alone remains unclear.

Screening and diagnosis of hepatitis D

Hepatitis D viral (HDV) infection is diagnosed by doing a simple blood test to detect high levels of Immunoglobulin G (IgG) and Immunoglobulin M (IgM) anti-HDV, and is thereafter confirmed by detection of HDV RNA in serum.

However, HDV diagnostics (tests to diagnose HDV) are not widely available and there is no standardization for HDV RNA assays, which are used for monitoring response to antiviral therapy.

HBsAg is useful to monitor treatment response if quantitative HDV RNA is not available. Decreasing HBsAg levels often herald surface antigen loss and HDV clearance, although surface antigen loss is rare in treatment.

Treatment of hepatitis D

Current guidelines generally recommend Pegylated interferon alpha for at least 48 weeks irrespective of on-treatment response patterns. While the overall rate of sustained virological response is low, this treatment is an independent factor associated with a lower likelihood of disease progression.

More efforts are needed to reduce the global burden of chronic hepatitis B and develop medicines that are safe and effective against hepatitis D and are affordable enough to be deployed on a large scale to those who are most in need.

Prevention of hepatitis D

Prevention and control of HDV infection requires prevention of HBV transmission through hepatitis B immunization, blood safety practices, injection safety (safe injection practices in health care settings), and harm reduction services with clean needles and syringes. Hepatitis B immunization does not provide protection against HDV for those already HBV infected.

Reference(s)
1). World Health Organization (July 2020): Hepatitis D. Available Online.
2). Centers for Disease Control (June 2020): Hepatitis D information. Available Online.
3). Stockdale AJ, Kreuels B, Henrion MYR, Giorgi E, Kyomuhangi I, de Martel C, Hutin Y, Geretti AM (2020). The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 23 April 2020; https://doi.org/10.1016/j.jhep.2020.04.008. Available Online.
4). NICE Clinical guideline [CG165] (June 2013). Antiviral treatment for Hepatitis B (chronic): Adults who are co-infected with hepatitis D. Available Online.