Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Robert Heimer

Second Advisor

Joseph K. Lim

Abstract

Chronic hepatitis B (CHB) remains a significant global health burden despite advances in antiviral therapy. Current treatments, including nucleoside analogs (NAs) and pegylated interferon (Peg-IFN), effectively suppress viral replication but rarely achieve functional cure, defined as sustained hepatitis B surface antigen (HBsAg) loss. Emerging therapeutic strategies focus on antigen reduction and immune modulation to overcome the limitations of existing therapies.

Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) offer promising approaches by directly targeting viral RNA to reduce HBsAg levels. Clinical trials of ASOs such as bepirovirsen and siRNAs such as JNJ-3989 and VIR-2218 have shown substantial HBsAg declines, but post-treatment rebounds remain a challenge. In parallel, immune-modulatory therapies, including therapeutic vaccines, checkpoint inhibitors, and toll-like receptor (TLR) agonists, aim to restore HBV-specific immune responses. Trials combining bepirovirsen or siRNA therapies with Peg-IFN have yielded mixed results, with limited sustained efficacy but increased adverse effects. Novel agents such as therapeutic vaccines (VTP-300, BRII-179) and HBsAg-targeting antibodies (Tobevibart) are under investigation to enhance immune clearance.

This review evaluates the latest advances in CHB therapy clinical trials, highlighting the need for combination regimens targeting both viral suppression and immune restoration. While significant progress has been made, achieving a functional cure will likely require multi-modal approaches integrating direct antiviral agents with immunotherapies to sustain long-term viral control.

Comments

This is an Open Access Thesis.

Download
Open Access

This Article is Open Access

Share

COinS