Hepatitis D virus (HDV) is a satellite virus that requires the hepatitis B surface antigen (HBsAg) from Hepatitis B virus (HBV) to assemble infectious particles. It has a circular negative‑sense single‑stranded RNA genome (~1.7 kb) encoding the small and large hepatitis delta antigen (HDAg), and it is the sole member of the genus Deltavirus.
Classification, biology and pathogenesis
HDV is unlike typical hepatotropic viruses because it cannot produce its own envelope proteins and therefore depends entirely on HBV for envelopment and transmission. Its genome forms a double‑stranded rod‑like structure and contains a self‑cleaving ribozyme. The viral RNA is replicated in the nucleus by host RNA polymerase II in a rolling‑circle mechanism and edited by host adenosine deaminase to generate the large form of HDAg. The small HDAg is required for replication, whereas the large HDAg inhibits replication and promotes packaging. Eight genotypes (HDV‑1 to HDV‑8) have been identified; genotype 1 is globally distributed, genotypes 2 and 4 are in Asia, genotype 3 in the Amazon basin, and genotypes 5–8 in Africa. Infection is acquired parenterally through exposure to blood or other body fluids; high‑risk groups include people who inject drugs, individuals requiring frequent blood transfusions, and persons with multiple sexual partners. When HDV and HBV are acquired simultaneously (co‑infection), most patients develop an acute self‑limited hepatitis, whereas superinfection of a chronic HBV carrier often results in severe disease, rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma. There is no specific curative therapy; pegylated interferon‑alpha has modest efficacy, and the entry inhibitor bulevirtide was recently licensed in the European Union. Preventing HBV infection through vaccination remains the most effective way to prevent HDV.
Notable outbreaks and clinical significance
HDV has been implicated in major public health problems in regions with intermediate or high HBV prevalence. In southern Italy during the 1970s and 1980s, HDV superinfection was responsible for severe epidemics of fulminant hepatitis. Endemic clusters of genotypes 5–8 contribute to a high burden of cirrhosis in central Africa. In the Amazon region, genotype 3 is associated with fulminant hepatitis outbreaks among young adults. In recent decades, widespread HBV vaccination has led to a marked decline in HDV incidence in countries such as Italy and Taiwan, but outbreaks continue among injection drug users in Eastern Europe and parts of Russia. Detection relies on measuring anti‑HDV antibodies and HDV RNA; treatment is based on long‑term pegylated interferon‑alpha, with variable response rates depending on genotype. Bulevirtide, an entry inhibitor targeting the sodium taurocholate co‑transporting polypeptide (NTCP) receptor, offers a new therapeutic option and is being integrated into clinical practice. HDV remains a clinically important pathogen because it amplifies the pathogenicity of HBV and accelerates progression to cirrhosis. Continued surveillance, harm reduction strategies and global HBV immunization are essential to reduce its burden and prevent outbreaks. Related Terms: Hepatitis B Virus, Deltavirus, Hepatitis C Virus, Hepatitis E Virus, Pegylated interferon