Hepatitis D virus (HDV) is a defective virus with circular, single-stranded genomic
RNA which needs hepatitis B virus (HBV) as a helper virus for virion assembly and infectivity. HDV virions are composed of a circular shape HDV
RNA and two types of
viral proteins, small and large HDAgs, surrounded by HBV
surface antigen (
HBsAg). The
RNA polymerase II from infected hepatocytes is responsible for synthesizing RNAs with positive and negative polarities for HDV, as the virus does not code any
enzyme to replicate its genome. HDV occurs as
co-infection or super-
infection in up to 5% of
HBsAg carriers. A recent multi-center study highlighted that pegylated
interferon α-2a (PEG-IFN) is currently the only treatment option for
delta hepatitis.
Nucleotide/
nucleoside analogues, which are effective against HBV, have no relevant effects on HDV. However, additional clinical trials combining PEG-IFN and
tenofovir are currently ongoing. The molecular interactions between HDV and HBV are incompletely understood. Despite fluctuating patterns of HBV viral load in the presence of HDV in patients, several observations indicate that HDV has suppressive effects on HBV replication, and even in triple
infections with HDV, HBV and HCV, replication of both concomitant viruses can be reduced. Additional molecular virology studies are warranted to clarify how HDV interacts with the helper virus and which key cellular pathways are used by both viruses. Further clinical trials are underway to optimize treatment strategies for
delta hepatitis.