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Review
. 2021 Feb 22;11(2):169.
doi: 10.3390/life11020169.

HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges

Caterina Sagnelli  1 , Evangelista Sagnelli  1 , Antonio Russo  1 , Mariantonietta Pisaturo  1 , Laura Occhiello  1 , Nicola Coppola  1
Affiliations
Review

HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges

Caterina Sagnelli et al. Life (Basel). .

Abstract

Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5-8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20-30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.

Keywords: HDV; epidemiology; hepatitis D; pathogenesis; therapeutics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hepatitis B virus (HBV) shares its small, medium and large hepatitis B surface antigens (HBsAg) with hepatitis D virus (HDV), acting as a helper virus of HDV.
Figure 2
Figure 2
Action of direct anti-HDV agents on the HDV life circle. HDV enters the hepatocyte through NTCP. The replication is carried out in the nucleus. Large HDAg is farnesylated in the cytoplasm. Assembly ends in the Golgi apparatus with the bond between HBsAg and HDAg. Bulevirtide inhibits NTCP (entry), lonafarnib inhibits prenylation (farnesylation, assembly), NAPs inhibit NTCP (entry), farnesylation (assembly) and release. Footnotes: NTCP, sodium taurocholate co-transporting polypeptide; HDV, hepatitis D virus; HDAg, hepatitis D antigen; L-HDAg, large hepatits D antigen; HBV, hepatitis B virus; NAPs, nucleic acid polymers.
See this image and copyright information in PMC

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