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Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure

Tarik Asselah, Dimitri Loureiro, Nathalie Boyer

    The Lancet. Gastroenterology & Hepatology
    |October 15, 2019
    PubMed

    Insights

    Chronic hepatitis B virus (HBV) infection affects millions globally. New direct-acting antivirals targeting the HBV lifecycle offer hope for more effective treatments beyond current options.

    Area of Science:

    • Hepatology
    • Virology
    • Drug Development

    Background:

    • Chronic hepatitis B virus (HBV) infection impacts over 257 million people worldwide, causing nearly 1 million annual deaths from liver cirrhosis and cancer.
    • Current HBV treatments like interferon-alfa and nucleoside analogues have limitations in efficacy, tolerability, and achieving a cure (HBsAg loss).

    Purpose of the Study:

    • To review the HBV lifecycle as a basis for developing novel therapeutic strategies.
    • To discuss emerging direct-acting antiviral (DAA) approaches targeting specific steps in HBV replication.

    Main Methods:

    • Review of current scientific literature on HBV pathogenesis and antiviral drug development.
    • Analysis of potential molecular targets within the HBV lifecycle for therapeutic intervention.

    Main Results:

    • Understanding the HBV lifecycle reveals multiple points for therapeutic targeting.
    • Several classes of direct-acting antivirals are in development, including entry inhibitors, capsid assembly modulators, cccDNA/RNA targeting drugs, and HBsAg secretion inhibitors.

    Conclusions:

    • Novel direct-acting antivirals targeting the HBV lifecycle represent a promising avenue for improved hepatitis B treatment.
    • Further research and development are crucial to overcome limitations of current therapies and achieve a functional cure for HBV infection.

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