Innovations in Antiviral Therapy for Chronic Hepatitis B: From Clinical Trials to Practice

Chronic hepatitis B is often framed purely as a viral disease, but immune suppression from surface antigen excess is central to how it behaves. This episode examines why targeting that immune dimension is essential to curing it.

Chronic hepatitis B remains highly prevalent yet chronically underdiagnosed in the United States. This episode reviews global and domestic epidemiology, new universal screening guidance, and a health-system model built to close the gap.

Unlike hepatitis C, chronic hepatitis B does not always progress through classic fibrosis, making liver cancer possible without significant liver damage. This episode reviews how genomic integration drives that risk and how monitoring should adapt.

Quantitative hepatitis B surface antigen testing is emerging as a critical tool for identifying which patients may respond best to next-generation therapies. This episode reviews new guideline recommendations and finite-duration therapy conversations.

Guideline inconsistency and treatment thresholds continue to create gaps in chronic hepatitis B care, particularly in primary care settings. This episode also examines what functional cure means for cancer risk and long-term antiviral safety.

Hepatitis B and hepatitis C behave nothing alike once treatment succeeds. This episode explains why hepatitis B's genomic integration makes true virologic cure fundamentally more complex than hepatitis C clearance.

Combination regimens, monoclonal antibodies, and gene therapy aimed at de-integrating viral DNA are reshaping what a hepatitis B cure could look like. This episode looks ahead to the next five to ten years

Dr. Chung welcomes Dr. Robert Gish to the program, who introduces himself as medical director of the Hepatitis B Foundation, an academic appointee at UCSD, Loma Linda, and the University of Nevada, Las Vegas, and a clinician who sees patients with hepatitis B across five active clinic sites, where the disease makes up roughly 10% of his practice.

Bepirovirsen's antisense mechanism raises a genuinely unsettled question: how much of its effect comes from direct antiviral activity versus an unexpected immune response. This episode unpacks that debate.

The Be Well trials narrowed eligibility to a specific surface antigen window, a design choice with real implications for which patients could benefit first. This episode reviews that rationale and its practice impact.

A roughly 20% functional cure rate is meaningful, but it comes with a safety profile that demands scrutiny in patients already doing well on suppressive therapy. This episode weighs that tradeoff.

A newer generation of capsid assembly modulators may finally move the needle on surface antigen, something earlier compounds in this class could not achieve. This episode explores that shift.

Early signals from a TLR9 agonist point to a role for innate immune modulation, though likely as one piece of a larger combination strategy rather than a standalone cure. This episode explains why.

E-antigen-positive disease looks very different depending on where in the world a patient lives, shaping who stands to benefit most from emerging T-cell vaccine strategies. This episode explores that global divide.

Realizing functional cure at scale will take more than new drugs; it requires infrastructure, testing, and patient engagement working in concert. This episode closes the series with a roadmap for that shift.