Does hepatitis delta virus have a preference for hepatitis B virus genotype? A systematic review of the literature

Hepatitis delta virus (HDV) is a deficient virus that requires the surface proteins of Hepatitis B virus (HBV) to complete its replication. HDV is thus only found in those already infected with HBV (~5% worldwide). There are eight different HDV genotypes (1-8) and 10 HBV genotypes (A-J), each having fairly distinct geographic distributions. While their pairings may be coincidental based on epidemiological occurrence, some evidence exists regarding possible virologic basis for genotype dominance and patterns. Here we sought to determine which HBV genotype is most often linked with active HDV infection and speculate on whether this may represent a viral 'preference'. Electronic databases with OVID Medline were comprehensively searched for studies published between 1977 and 2022 indexing the word 'genotype' and all permutations of 'HDV' (hepatitis D virus, hepatitis delta, etc.). Primary studies of patient samples reporting genotype data for either or both of HDV and HBV were tabulated. The initial search revealed 419 articles and was narrowed to 133 studies reporting genotype data for either or both HBV and HDV. We limited our search to cases with detectable HDV RNA. These represented over 5800 samples from over 70 countries. Of these, 1947 samples had paired genotype data for both viruses. The most common pairing was HDV-1 with HBV-D, but it remains unclear whether this represents a viral 'preference' or mere co-endemicity of the two viruses. Determining if there is a virologic link between HBV and HDV genotypes may have important implications for emerging HDV and HBV research.