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Review
. 2020 Oct 15:7:2049936120965027.
doi: 10.1177/2049936120965027. eCollection 2020 Jan-Dec.

Advances in hepatitis B therapeutics

Vicente Soriano  1 , Pablo Barreiro  2 , Edward Cachay  3 , Shyamasundaran Kottilil  4 , José V Fernandez-Montero  5 , Carmen de Mendoza  6
Affiliations
Review

Advances in hepatitis B therapeutics

Vicente Soriano et al. Ther Adv Infect Dis. .

Abstract

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a 'functional cure', with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes.

Keywords: antiviral therapy; bulevirtide; cccDNA; chronic hepatitis B; combination therapy; gene editing; hepatitis delta; resistance.

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Conflict of interest statement

Conflict of interest: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
HBV life cycle. HBV, hepatitis B virus.
Figure 2.
Figure 2.
Main biomarker goals with distinct HBV therapies. HBV, hepatitis B virus.
Figure 3.
Figure 3.
Hepatitis delta virus life cycle and therapeutic targets. HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HDV, hepatitis delta virus; HDV-Ag, delta antigen; NAPs, nucleic acid polymers; NTCP, sodium taurocholate co-transporting polypeptide.
Figure 4.
Figure 4.
Global distribution of HIV and HBV. HBV, hepatitis B virus.
See this image and copyright information in PMC

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