DLP-201

The coexistence of hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb) during antiviral therapy is considered atypical in patients with chronic hepatitis B (CHB), and its clinical implications remain inadequately understood, particularly in pediatric patients. This study aimed to investigate the clinical characteristics of this coexistence pattern and its impact on the outcomes of combined antiviral therapy in children with CHB.

A total of 254 treatment‐naïve children diagnosed with HBeAg‐positive CHB were retrospectively enrolled. All patients received combination therapy with entecavir and interferon‐alpha/pegylated‐interferon‐alpha. Participants were categorized into a coexistence group and a control group based on whether HBeAg and HBeAb coexisted during treatment period. Clinical characteristics and treatment outcomes were compared, and Cox regression analysis was used to evaluate factors influencing the coexistence pattern and its association with antiviral responses.

The incidence of HBeAg and HBeAb coexistence during antiviral therapy was 35.43% (90/254). This pattern was associated with the higher HBV DNA levels (hazard ratio [HR] = 1.25, p  = 0.009) at baseline. Notably, children in the coexistence group demonstrated a greater likelihood of achieving HBsAg loss (HR = 2.58, p  < 0.001), HBeAg loss (HR = 2.23, p  < 0.001) and HBV‐DNA undetectability (HR = 1.42, p  = 0.034).

The HBeAg/HBeAb coexistence pattern is relatively common during antiviral therapy in children and is associated with significantly improved treatment outcomes. These findings highlight the importance of monitoring HBeAg/HBeAb dynamics and continuing treatment during this critical phase.

Chronic hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. Although humans produce 12 subtypes of interferon-alpha (IFN-α), IFN-α2a has been the only commonly used treatment against HDV. Previously, we characterized eight HDV genotype isolates with varying replication kinetics. Herein, we systematically investigated the antiviral efficacy of IFN-α2a and other IFN-α subtypes against HDV genotypes 1–8 during de novo infection, cell mitosis, and in quiescent cells. Our findings revealed that IFN-α2a exhibits potent but varied efficiency against HDV 1–8 isolates upon de novo infection and cell mitosis. Conversely, HDVs in resting cells are resistant to IFN-α2a treatment and the IFN-containing cytokine cocktail collected from peripheral blood mononuclear cells stimulated with TLR7/8 agonist. Mechanistically, both ADAR1 p110 and p150 promote L-HDAg production and inhibit HDV replication. ADAR1 p150, rather than p110, enhances the anti-HDV efficacy of IFN-α during de novo infection and cell mitosis, but not in resting cells. Moreover, different subtypes of IFN-α exhibit varying anti-HDV activities in both de novo infection and cell mitosis, due to their disparity in activating interferon responses. Among these, IFN-α2a, IFN-α10, and IFN-α14 exhibit the strongest anti-HDV activity and synergize with bulevirtide in suppressing HDV replication. In conclusion, the anti-HDV efficacy of IFN-α depends on multiple factors, including HDV genotypes, ADAR1 p150 level, IFN-α subtypes, and HDV’s different survival strategies. These findings provide valuable implications for the development and optimization of IFN-based therapies.

Chronic hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis. This study comprehensively evaluated the antiviral efficacy of interferon-alpha (IFN-α) subtypes across eight HDV genotypes during de novo infection, cell mitosis, or in quiescent cells. Herein, we found that IFN-α exhibits potent but varied efficiency against HDV 1–8 isolates upon de novo infection and cell mitosis. Conversely, HDVs in resting cells are resistant to IFN-α subtypes, regardless of the cellular ADAR1 levels. Among different subtypes, IFN-α2a, IFN-α10, and IFN-α14 exhibit the strongest anti-HDV activity and synergize with bulevirtide in suppressing HDV replication. These findings provide crucial insights into the optimization of IFN-based monotherapy and combinational therapy against chronic HDV infection.