Hepatitis D

Hepatitis D is an inflammatory liver disease caused by the hepatitis delta virus (HDV), a defective RNA virus classified in the genus Deltavirus within the realm Ribozyviria. HDV is considered a satellite virus because it cannot replicate independently and requires the presence of hepatitis B virus (HBV) to complete its life cycle. The HDV virion is a small, spherical enveloped particle approximately 36 nanometers in diameter, containing host phospholipids and three hepatitis B surface antigen proteins that facilitate cellular entry. The viral genome is a negative-sense single-stranded RNA molecule surrounded by approximately 200 molecules of hepatitis delta antigen (HDAg), which exists in both small and large isoforms produced through RNA editing.

Hepatitis D presents in two distinct clinical patterns depending on the timing of HBV and HDV infection. Coinfection, involving simultaneous acquisition of both viruses, typically causes acute hepatitis with symptoms appearing three to seven weeks after initial infection, including fever, fatigue, loss of appetite, nausea, vomiting, dark urine, pale stools, and jaundice; recovery is usually complete, and progression to chronic hepatitis D occurs in fewer than 5 percent of cases. Superinfection, in which HDV infects an existing chronic HBV carrier, represents the most severe form of viral hepatitis and leads to chronic hepatitis D in the majority of instances, with rapid progression to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The combination of HDV and HBV carries the highest fatality rate among all hepatitis infections at approximately 20 percent.

Global HDV prevalence affects nearly 5 percent of the estimated 240 million people living with chronic HBV infection, translating to approximately 12 to 48 million individuals worldwide depending on estimation methodology. The disease exhibits marked geographical heterogeneity, with identified hotspots including Mongolia, the Republic of Moldova, and countries in western and central Africa; the virus is also highly prevalent in the Mediterranean region, sub-Saharan Africa, the Middle East, and northern South America. Populations at elevated risk for HDV-HBV coinfection include indigenous communities, recipients of haemodialysis, and people who inject drugs. HDV has been classified as carcinogenic to humans (Group 1) by the International Agency for Research Cancer, and HDV coinfection may explain approximately one-fifth of liver disease and liver cancer cases among HBV-infected individuals.

Hepatitis D is transmitted through blood-borne routes and other bodily fluids in a manner analogous to hepatitis B virus. Primary transmission pathways include direct contact with infected blood, sexual intercourse, and vertical transmission from mother to child before or around birth; household transmission within families has also been documented in endemic areas. Infection can occur either as simultaneous HBV-HDV coinfection or as superinfection in individuals already chronically infected with HBV. Persons lacking immunity to HBV, whether through natural infection or hepatitis B vaccination, remain susceptible to HDV infection since HDV cannot establish infection without concurrent HBV.

Populations at elevated risk for HDV infection include individuals with chronic hepatitis B virus infection, particularly those from regions with high HDV endemicity such as Mongolia, the Republic of Moldova, and parts of western and central Africa. Specific high-risk groups identified in epidemiological studies comprise indigenous populations, recipients of haemodialysis therapy, and people who inject drugs. Persons who are not immune to HBV through vaccination or prior natural infection remain susceptible to HDV acquisition, and household contacts of infected individuals in endemic areas face increased exposure risk.

Hepatitis D infection is preventable through universal hepatitis B immunization, which confers protection against both HBV and the dependent HDV. Since HDV requires HBV for replication, preventing HBV infection inherently prevents HDV acquisition. Public health measures targeting high-risk populations, including harm reduction programs for people who inject drugs and infection control practices in healthcare settings, serve as secondary prevention strategies. Novel therapeutic agents with improved safety profiles and treatment outcomes have recently received approval in Europe, representing an important advance in clinical management for those already infected.

Hepatitis D surveillance presents significant challenges due to limited diagnostic availability, particularly in low- and middle-income countries where the disease burden is often highest. Diagnosis of chronic HDV requires serological testing to demonstrate exposure combined with molecular methods to detect HDV RNA and confirm active viremic infection; however, standardization of HDV RNA assays remains limited, and such testing is not widely accessible globally. Surveillance systems should incorporate HDV testing within existing HBV monitoring frameworks, with particular attention to populations identified as high-risk, including indigenous communities, haemodialysis recipients, and people who inject drugs. Geographic hotspots warrant enhanced surveillance intensity, and integration of HDV screening into hepatocellular carcinoma monitoring programs among HBV-infected individuals may improve case detection.

1. 1 WHO Fact Sheet. Hepatitis D.
2. 2 Wikidata. hepatitis D.
3. 3 Wikipedia. Hepatitis D - Wikipedia.

ICD-10

B17.0

ICD-11

1E50.3

Total cases

5K

Peak month

2017-09

Coverage

2 reporting countries · 2000-01-01 → 2026-04-01