LTβR Agonists
Recently, Lucifora and colleagues were able to show that IFNα treatment results in non-cytotoxic degradation of a substantial fraction of the cccDNA pool mediated by a cellular deaminase designated APOBEC3A.[82]Importantly, induction of another deaminase from the same family, APOBEC3B through the activation of Lymphotoxin β receptor (LTβR), leads to a more robust cccDNA deamination and degradation as compared to IFNα. LTβR agonists were active at low doses, did not cause any toxicity nor modification of genomic DNA. It is tempting to speculate that this study provides a plausible mechanism for cytokine-dependent non-cytopathic elimination of cccDNA, in addition to providing an exciting therapeutic option.
News & Perspective > Liver International
New Therapies for Chronic Hepatitis b
Maya Bitton Alaluf; Amir Shlomai
DISCLOSURES
Liver International. 2016;36(6):775-782.
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IN THIS ARTICLE
Conclusions and Future Perspectives
The advent of new antiviral therapy against HCV infection, which has been shown to remedy most cases of chronic HCV, has brought about a plethora of enthusiasm in duplicating the success in HBV therapeutics.
In this review, we aim to briefly summarize the future therapeutics for HBV while schematically dividing them into three elements – those directed at specific steps in viral life cycle and spread, those aimed at augmenting and restoring the host immune responses and those specifically targeting cccDNA.
Although most agents showed great promise in vitro, data from clinical trials seem to be mostly premature at this point. It is likely that an integrative antiviral approach combining components of these elements will be needed to surmount CHB infection (Fig. 1). Clearly, the subsequent steps of clinical trials will be fascinating to follow, but the intense efforts done in the field hold promise that cure for this long-standing, debilitating and sometimes fatal disease, is already within our reach.
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Figure 1.
Integration of therapeutic strategies to better control HBV infection. Current efforts to develop innovative strategies to better control HBV are divided into three interdependent arms that complement and synergize each other: Interference with viral life cycle and spread, immune modulation and directly targeting cccDNA. The elimination of cccDNA is the ultimate goal in future therapy and is a perquisite for viral eradication and cure.