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ABI-H0731 + peginterferon alfa-2a is an investigational combination therapy for chronic hepatitis B. **ABI-H0731** is a first-generation hepatitis B virus (HBV) core protein inhibitor; it acts by selectively inhibiting HBV DNA replication and suppressing covalently closed circular DNA (cccDNA) formation. Its mechanism is direct inhibition of the HBV core protein, preventing encapsidation of pregenomic RNA (pgRNA), disrupting nucleocapsids, and halting viral DNA synthesis and new cccDNA formation[1][5]. **Peginterferon alfa-2a** is a pegylated recombinant human interferon that activates the innate antiviral response by binding type I interferon receptors and inducing the JAK/STAT pathway, resulting in antiviral, immunomodulatory, and antiproliferative effects[2][6]. Peginterferon alfa-2a is approved for hepatitis B and C but has significant adverse effect profiles.[2][4] The combination aims to deliver complementary antiviral mechanisms and potentially higher rates of HBV functional cure than monotherapy.
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