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Review
. 2022 Aug 10;14(8):1749.
doi: 10.3390/v14081749.

A Review of HDV Infection

Gian Paolo Caviglia  1 , Alessia Ciancio  1   2 , Mario Rizzetto  1
Affiliations
Review

A Review of HDV Infection

Gian Paolo Caviglia et al. Viruses. .

Abstract

Hepatitis D is the most severe viral hepatitis. Hepatitis D virus (HDV) has a very small RNA genome with unique biological properties. It requires for infection the presence of hepatitis B virus (HBV) and is transmitted parenterally, mainly by superinfection of HBsAg carriers who then develop chronic hepatitis D. HDV has been brought under control in high-income countries by the implementation of HBV vaccination, and the clinical pattern has changed to a chronic hepatitis D seen in ageing patients with advanced fibrotic disease; the disease remains a major health concern in developing countries of Africa and Asia. Every HBsAg-positive subject should be tested for HDV serum markers by reflex testing, independently of clinical status. Vaccination against HBV provides the best prophylaxis against hepatitis D. The only therapy available so far has been the poorly performing Interferon alfa; however, several new and promising therapeutic approaches are under study.

Keywords: Kolmioviridae; anti-HD; bulevirtide; hepatitis D; hepatitis D virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hepatitis delta virus. Defective, dependent on biological help from the HBV, present only in HBsAg-positive subjects (HBsAg carriers). Virion: 36 nm particle, enveloped in HBsAg. Genome: 1.7 Kb RNA. Abbreviations: HBsAg, hepatitis B surface antigen; HDAg, hepatitis D antigen.
Figure 2
Figure 2
Replication of HDV-RNA. The HDV is replicated by DNA-dependent RNA polymerases of the hepatocytes, redirected to copy the viral RNA. The host RNA polymerases elongate a multimeric linear RNA transcript over the circular genome, which is then cut to monomeric linear HDV-RNA by the ribozyme and ultimately ligated into the circular infectious form by cell ligases.
Figure 3
Figure 3
Prevalence of anti-HD in HBsAg carriers at low and high risk of HDV recruited at different sites (extrapolated from data in Italy in the 1980s). Abbreviations: anti-HD, antibodies to hepatitis D; HCC, hepatocellular carcinoma.
Figure 4
Figure 4
Contemporary HDV prevalence. Abbreviations: HBV, hepatitis B virus; HDV, hepatitis D virus.
Figure 5
Figure 5
Decline in anti-HD in HBsAg carriers with liver disease in Italy by the end of last century and return of the antibody with migratory fluxes in the last two decades. Abbreviations: anti-HD, antibodies to hepatitis D; n, number.
Figure 6
Figure 6
Features of HDV Italians recruited at different time-points. * p value < 0.001. 1 [48], 2 [49] 3 [45]. HDV-RNA measured by a qualitative methods, b semiquantitative PCR, and c quantitative PCR. Abbreviations: ALT, alanine aminotransferase; HBsAg, hepatitis B surface antigen; pts, patients.
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