Strategies to Achieve Functional Cure in HBV: Focus on siRNA

Abstract Purpose of Review Chronic hepatitis B (HBV) infection remains a major global contributor to liver disease, yet current antiviral therapies infrequently achieve a functional cure. This review highlights emerging data on 2 novel agents that are designed to suppress viral antigen expression and potentially restore immune control of the infection. Recent Findings Imdusiran and bepirovirsen are 2 leading experimental therapies that target HBV RNA and have shown meaningful reductions in hepatitis B surface antigen and occasional instances of functional cure. Summary The emergence of RNA-targeted therapies marks a pivotal advancement in HBV treatment, shifting the focus beyond viral suppression to include immune restoration. A strong, coordinated immune response is needed, as evidenced by seroconversion patterns in treatment-responsive individuals. Moving forward, successful HBV cure strategies will likely involve combination regimes, pairing RNA-targeted agents with nucleos(t)ide analogues for viral suppression or immunomodulators like pegylated interferon-alfa-2a to effectively reestablish immune control.