Editor’s Note
The current treatment options for chronic hepatitis B (CHB) primarily include long-term nucleos(t)ide analogs (NA) therapy and short-term interferon therapy. Although these approaches can control viral replication to some extent, only a small proportion of patients achieve functional cure. Pegylated interferon-α (PegIFN-α) is an important option in CHB treatment due to its dual role in directly inhibiting the virus and modulating the immune system. However, the efficacy of PegIFN-α varies significantly among patients, and not all benefit from this treatment. Therefore, there is an urgent need to identify biomarkers that can predict the treatment outcomes. Recently, a study led by Dr. Carolina Boni from the University of Parma, Italy, published in Gut, unveiled the potential of hepatitis B core-related antigen (HBcrAg) levels as a predictor for CHB patients’ response to PegIFN-α treatment. This discovery provides a new scientific basis for personalized treatment of CHB patients.
This multicenter study, conducted across Italy, aimed to evaluate the immunomodulatory effects of PegIFN-α in HBeAg-negative CHB patients under NA suppression and to explore whether HBcrAg levels can serve as a predictive marker for the response to PegIFN-α treatment. The ultimate goal is to provide scientific guidance for personalized treatment strategies in CHB.
The study included 53 HBeAg-negative CHB patients from six clinical research centers in Italy, all of whom had achieved complete viral suppression with long-term NA therapy. These patients were randomly assigned to either the experimental group (receiving 48 weeks of PegIFN-α treatment) or the control group (continuing NA therapy). The research team measured patients’ serum hepatitis B surface antigen (HBsAg) and HBcrAg levels, as well as immune parameters such as peripheral blood natural killer (NK) cell phenotype and function, and hepatitis B-specific T-cell responses, before, during, and after treatment.
The results showed that PegIFN-α treatment significantly reduced HBsAg levels, particularly at 24 weeks after treatment completion.
Patients were divided into two groups based on the extent of HBsAg reduction: those with a reduction greater than 0.5 log10 (52%) and those with a reduction less than 0.5 log10 (48%). The findings revealed that patients with lower baseline HBcrAg levels exhibited a more significant reduction in HBsAg after treatment.
Further analysis demonstrated a strong correlation between HBsAg reduction and enhanced hepatitis B-specific T-cell responses. Specifically, patients with a reduction greater than 0.5 log10 in HBsAg at 24 weeks post-treatment exhibited stronger hepatitis B-specific CD4+ and CD8+ T-cell responses, including higher levels of IFN-γ, TNF-α, and IL-2 cytokine production. Multivariate regression analysis identified IFN-γ-producing CD8+ T cells as the immune parameter most strongly associated with HBsAg reduction.
Based on these findings, the researchers concluded that a baseline HBcrAg level below 3.05 logU/mL can serve as an independent predictor of a favorable response to PegIFN-α treatment, with an accuracy of 84%.
Researcher’s Perspective
Dr. Carolina Boni: The clinical significance of our study lies in several key areas. First, it provides strong evidence that baseline HBcrAg levels can serve as an important biomarker for predicting CHB patients’ response to PegIFN-α treatment. Second, personalized treatment—selecting patients with lower baseline HBcrAg levels for PegIFN-α therapy—can enhance treatment efficacy and success rates, while minimizing unnecessary drug exposure and side effects. Additionally, this discovery opens new avenues for the precise treatment of CHB, contributing to the further optimization and advancement of CHB treatment strategies.
Although our study highlights the potential of HBcrAg levels in predicting treatment response, this finding still requires validation in larger patient cohorts. In the future, our research team plans to explore the combination of interferon with other novel antiviral and immunomodulatory agents to achieve a higher rate of functional cure.
