Overview
Hepatitis D is an inflammation of the liver caused by the hepatitis D virus (HDV), which 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 hepatocellular carcinoma and liver-related death.
Vaccination against hepatitis B is the only method to prevent HDV infection.
Geographical distribution
In a study published in the Journal of Hepatology in 2020 (1), conducted in collaboration with WHO, it was estimated that hepatitis D virus (HDV) affects nearly 5% of people globally 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 central Africa.
Transmission
The routes of HDV transmission, like HBV, occur through broken skin (via injection, tattooing etc.) or through contact with infected blood or blood products. Transmission from mother to child 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.
Chronic HBV carriers are at risk of 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 indigenous people, people who inject drugs and people with hepatitis C virus or HIV infection. The risk of co-infection also appears to be potentially higher in recipients of haemodialysis, men who have sex with men and commercial sex workers.
Symptoms
In acute hepatitis, simultaneous infection with HBV and HDV can lead to a mild-to-severe hepatitis with signs and symptoms of indistinguishable from those of other types of acute viral hepatitis infections. These features typically appear 3–7 weeks after initial infection and include fever, fatigue, loss of appetite, nausea, vomiting, dark urine, pale-coloured stools, jaundice (yellow eyes) and even fulminant hepatitis. However, recovery is usually complete, development of fulminant hepatitis is infrequent, and chronic hepatitis D is rare (less than 5% of acute hepatitis).
In a 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. Patients with HDV induced cirrhosis are at an increased risk of hepatocellular carcinoma (HCC); however, the mechanism in which HDV causes more severe hepatitis and a faster progression of fibrosis than HBV alone remains unclear.
Diagnosis
HDV infection is diagnosed by high levels of anti-HDV immunoglobulin G (IgG) and immunoglobulin M (IgM), 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.
Treatment
Pegylated interferon alpha is the generally recommended treatment for hepatitis D virus infection. Treatment should last for at least 48 weeks irrespective of the patient’s response. The virus tends to give a low rate of response to the treatment; however, the treatment is associated with a lower likelihood of disease progression.
This treatment is associated with significant side effects and should not be given to patients with decompensated cirrhosis, active psychiatric conditions and autoimmune diseases. Bulevirtide is one of the new promising treatments for hepatitis D.
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
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. Hepatitis B immunization does not provide protection against HDV for those already infected with HBV.
WHO response
Global health sector strategies on, respectively, HIV, viral hepatitis, and sexually transmitted infections for the period 2022–2030 (GHSSs) guide the health sector in implementing strategically focused responses to achieve the goals of ending AIDS, viral hepatitis (especially chronic hepatitis B and C) and sexually transmitted infections by 2030.
The GHSS recommend shared and disease-specific country actions supported by actions by WHO and partners. They consider the epidemiological, technological, and contextual shifts of previous years, foster learnings across the disease areas, and create opportunities to leverage innovations and new knowledge for effective responses to the diseases. They call to scale up prevention, testing and treatment of viral hepatitis with a focus to reach populations and communities most affected and at risk for each disease, as well as addressing gaps and inequities. They promote synergies under a universal health coverage and primary health care framework and contribute to achieving the goals of the 2030 Agenda for Sustainable Development.
WHO organizes annual World Hepatitis Day campaigns (as 1 of its 9 flagship annual health campaigns) to increase awareness and understanding of viral hepatitis. For World Hepatitis Day 2023, WHO focuses on the theme “One life, one liver” to illustrate the importance of the liver for a healthy life and the need to scale up viral hepatitis prevention, testing and treatment to prevent liver diseases and achieve the 2030 hepatitis elimination target.