Hepatitis D

27 July 2020

Key facts

  • Hepatitis D virus (HDV) is a virus that requires hepatitis B virus (HBV) for its replication. HDV infection occurs only simultaneously or as super-infection with HBV.
  • The virus is most commonly transmitted from mother to child during birth and delivery, as well as through contact with blood or other body fluids, including sex with an infected partner, injection-drug use that involves sharing needles, syringes, or drug-preparation equipment and needle sticks or exposures to sharp instruments.
  • Vertical transmission from mother to child is rare.
  • Hepatitis D virus (HDV) affects globally nearly 5% of people who have a chronic infection with hepatitis B virus (HBV).
  • Several geographical hotspots of high prevalence of HDV infection exist, including Mongolia, the Republic of Moldova, and countries in Western and Middle Africa.
  • Populations that are more likely to have HBV and HDV co-infection include people who inject drugs, indigenous populations and recipients of hemodialysis.
  • Worldwide, the overall number of HDV infection has decreased since 1980s. This trend is mainly due to a successful global HBV vaccination programme.
  • 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.
  • Currently, treatment success rates are generally low.
  • Hepatitis D infection can be prevented by hepatitis B immunization.

Hepatitis D is a liver disease in both acute and chronic forms caused by the hepatitis D virus (HDV) that requires HBV for its replication. Hepatitis D infection cannot occur in the absence of hepatitis B virus. 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.

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

Geographical distribution

In a study published in the Journal of Hepatology in 20201 that was conducted in collaboration with 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.

Transmission

The routes of HDV transmission are the same as for HBV: percutaneously or sexually through contact with infected blood or blood products. Vertical transmission 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.

Symptoms

Acute hepatitis: simultaneous infection with HBV and HDV can lead to a mild-to-severe or even fulminant 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 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 cirrhosis 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.

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.

Screening and diagnosis

HDV infection is diagnosed by high levels of Immunoglobulin G (IgG) and Immunoglobulin M (IgM) anti-HDV, and confirmed by detection of HDV RNA in serum.

However, HDV diagnostics 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

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

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

Prevention and control of HDV infection requires prevention of HBV transmission through hepatitis B immunization, blood safety, injection safety, and harm reduction services. Hepatitis B immunization does not provide protection against HDV for those already HBV infected.

WHO response

In May 2016, The World Health Assembly adopted the first “Global Health Sector Strategy on Viral Hepatitis, 2016-2021”. The strategy highlights the critical role of Universal Health Coverage and the targets of the strategy are aligned with those of the 2030 Sustainable Development Goals. The strategy has a vision of eliminating viral hepatitis as a public health problem and this is encapsulated in the global targets of reducing new viral hepatitis infections by 90% and reducing deaths due to viral hepatitis by 65% by 2030. Actions to be taken by countries and WHO Secretariat to reach these targets are outlined in the strategy.

While WHO does not have specific recommendations on hepatitis D, prevention of HBV transmission through hepatitis B immunization, including a timely birth dose, additional antiviral prophylaxis for eligible pregnant women,  blood safety, safe injection practices in health care settings, and harm reduction services with clean needles and syringes, are effective in preventing HDV transmission. WHO supports Member States in scaling up these evidence-based prevention measures.

Furthermore, to support countries in moving towards achieving the global hepatitis goals under the 2030 Sustainable Development Agenda, WHO is working in the following areas:

  • raising awareness, promoting partnerships and mobilizing resources;
  • formulating evidence-based policy and data for action
  • increasing health equities within the hepatitis response
  • preventing transmission; and
  • scaling up screening, care and treatment services.
WHO also marks World Hepatitis Day on 28 July every year to increase awareness and understanding of viral hepatitis. For World Hepatitis Day 2020, WHO is focusing on the theme “Hepatitis-free future” to highlight the importance of addressing the prevention of HBV (and HDV) infection, including through the prevention of mother-to-child transmission of HBV.

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1 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. Published online 23 April 2020; https://doi.org/10.1016/j.jhep.2020.04.008