Aetiology

Hepatitis D virus (HDV) is a small spherical RNA virus with an inner ribonucleoprotein and an outer envelope. The ribonucleoprotein contains the HDV RNA that consists of a single, circular, covalently closed strand of between 1676 and 1683 nucleotides that encodes the HDV antigen.[13] The International Committee on Taxonomy of Viruses has proposed classifying HDV into the Deltavirus genus of the Kolmioviridae family, which is part of the Ribozyviria realm.[4]

Although HDV can replicate inside the host cell, it uses the hepatitis B surface antigen to form the outer envelope, so hepatitis B virus (HBV) infection is required for HDV to propagate.[14]

The virus is transmitted via contaminated blood or blood products through percutaneous, permucosal, and sexual transmission.[15]

Pathophysiology

Two kinds of human HDV infection have been distinguished:[16]

  • Co-infection with HBV, whereby a person is infected simultaneously with both HDV and HBV

  • Superinfection, whereby a person who is already chronically infected with HBV acquires HDV.

Co-infection leads to acute HDV and HBV infection, which is usually a self-limited illness but is more likely than acute HBV infection alone to lead to severe illness and acute liver failure.[17] Since HDV is dependent on HBV, the progression to chronic infection mirrors that of chronic HBV infection, with younger age at infection predicting higher risk of chronicity.

Superinfection can present as a severe hepatitis, either in someone not known to have chronic HBV infection or as a flare of disease in someone with chronic HBV infection. Since the patient already has chronic HBV infection, progression to chronic HDV infection is almost universal.[18]

The mechanism of liver damage by HDV is unclear but presumably depends on the interaction of HDV genotype, host immune response, and activity of HBV.[19][20] Interestingly, HDV infection suppresses HBV replication - explaining why liver enzymes can be elevated in patients with chronic HBV infection despite negative HBV DNA levels.[21]

Classification

HDV genotype[3]

The International Committee on Taxonomy of Viruses has proposed classifying HDV into the Deltavirus genus of the Kolmioviridae family, which is part of the Ribozyviria realm.[4]

There are eight HDV genotypes (1 through 8) with different geographical distribution and likely different virulence and pathogenicity.

  • Genotype 1 is found mainly in North America, Europe, the Middle East, and north Africa.

  • Genotypes 2 and 4 are found in east Asia.

  • Genotype 3 is found in the Amazon Basin and South America.

  • Genotypes 5, 6, 7, and 8 are found in west and central Africa.

Genotypes 1 and 3 lead to more severe disease and genotype 5 is associated with better response to therapy.[5][6] There are also geographical differences in the risk of complications, with studies in Taiwan, where genotype 2 predominates, suggesting the risk of fulminant liver failure and cirrhosis or hepatocellular carcinoma is decreased compared with in genotype 1 HDV disease.[7][8]

Genotype testing of HDV is not routinely available and not part of the management approach.

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