Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Sep:121:69-81.
doi: 10.1016/j.antiviral.2015.06.014. Epub 2015 Jun 22.

Chronic hepatitis B: A wave of new therapies on the horizon

Timothy M Block  1 , Siddhartha Rawat  2 , Carol L Brosgart  3
Affiliations
Review

Chronic hepatitis B: A wave of new therapies on the horizon

Timothy M Block et al. Antiviral Res. 2015 Sep.

Abstract

This year marks the 50th anniversary of the discovery of the Australia antigen (Blumberg et al., 1965), which in 1967 was identified to be the hepatitis B virus (HBV) surface antigen. Even though several antiviral medications have been in use for the management of chronic HBV infection for more than 20years, sustained clearance of HBsAg, similar to the sustained viral response (SVR) or cure in chronic hepatitis C, occurs in only a minority of treated patients. Moreover, even after 10years of effective suppression of HBV viremia with current therapy, there is only a 40-70% reduction in deaths from liver cancer. Recent success in developing antivirals for hepatitis C that are effective across all genotypes has renewed interest in a similar cure for chronic HBV infection. In this article, we review a wave of newly identified drug targets, investigational compounds and experimental strategies that are now under clinical evaluation or in preclinical development. The paper forms part of a symposium in Antiviral Research on "An unfinished story: From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."

Keywords: Antiviral therapy; Chronic hepatitis B; Clinical trials; Hepatitis B virus.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Time-line of approval of hepatitis B therapeutics by the US Food and Drug Administration. Green: immunodulators (interferons); Blue: Direct-acting antivirals (polymerase inhibitors).
Figure 2
Figure 2
Categorization of therapeutics for management of chronic HBV infection. Direct-acting antivirals (DAAs) interfere with a specific step in viral replication. Host-targeted antivirals (HTA) inhibit viral replication by modifying host cell function.
Figure 3
Figure 3
Major intracellular steps in the HBV life cycle for which DAAs or HTAs could be developed. Each step is discussed in this review, and novel therapies targeting many of them are the subject of articles in this symposium.
Figure 4
Figure 4
Therapeutics in development for the management of chronic HBV infection. (A) Investigational agents in Phase 1 clinical trials at the time of writing this review. The NCT number (wherever applicable) after the company's name is the clinicaltrials.gov identifier. (B) Investigational agents in preclinical stages. The stage of development is indicated, from in vitro identification through animal efficacy and ultimately human clinical trials. DAAs are highlighted in green and HTAs in blue. Investigational agents that have failed or have been stopped are shown in red. See text for citations. When we were unable to find a published reference, we cite the sponsor's website.
Figure 4
Figure 4
Therapeutics in development for the management of chronic HBV infection. (A) Investigational agents in Phase 1 clinical trials at the time of writing this review. The NCT number (wherever applicable) after the company's name is the clinicaltrials.gov identifier. (B) Investigational agents in preclinical stages. The stage of development is indicated, from in vitro identification through animal efficacy and ultimately human clinical trials. DAAs are highlighted in green and HTAs in blue. Investigational agents that have failed or have been stopped are shown in red. See text for citations. When we were unable to find a published reference, we cite the sponsor's website.
See this image and copyright information in PMC

References

    1. Adam BL, Qu Y, Davis JW, Ward MD, Clements MA, Cazares LH, Semmes OJ, Schellhammer PF, Yasui Y, Feng Z, Wright GL., Jr. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer research. 2002;62:3609–3614. - PubMed
    1. Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. The New England journal of medicine. 2014;370:1483–1493. - PubMed
    1. Arends P, Sonneveld MJ, Zoutendijk R, Carey I, Brown A, Fasano M, Mutimer D, Deterding K, Reijnders JG, Oo Y, Petersen J, van Bommel F, de Knegt RJ, Santantonio T, Berg T, Welzel TM, Wedemeyer H, Buti M, Pradat P, Zoulim F, Hansen B, Janssen HL. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians. Gut. 2014 - PubMed
    1. Arrowhead Arrowhead Provides Update on IND for ARC-520 Phase 2b Study. 2015b.
    1. Aspinall EJ, Hawkins G, Fraser A, Hutchinson SJ, Goldberg D. Hepatitis B prevention, diagnosis, treatment and care: a review. Occup Med (Lond) 2011;61:531–540. - PubMed

Publication types

MeSH terms

Substances