Background This study aims to identify the key factors influencing the loss of hepatitis B surface antigen (HBsAg) and durability of functional cure. Understanding these factors is crucial for identifying patient groups that may benefit from a pegylated interferon alpha (Peg-IFN-α) induced “functional cure” for hepatitis B, as well as for optimizing strategies to achieve and sustain HBsAg loss. Methods The study utilized real-world data, including 378 patients with chronic hepatitis B virus (HBV) infection who received treatment with Peg-IFN-αfor 24 weeks or longer. Patients were grouped based on their response at 24 and 48 weeks of treatment, and predictive factors for the response were calculated through regression analysis. Additionally, 195 subjects who achieved HBsAg loss were included to assess factors influencing the durability of HBsAg loss. The primary endpoint was reverse seroconversion of HBsAg (HBsAg-RS). Results The findings suggest that the degree of HBsAg at baseline and HBsAg decline at 12/24 weeks of treatment is critical for predicting treatment response. Factors affecting durability include age, nucleoside treatment, baseline hepatitis B core antibody (anti-HBc) levels, the consolidation of Peg-IFN-α therapy, and hepatitis B surface antibody (anti-HBs) levels at the time of treatment discontinuation. Higher anti-HBs levels at discontinuation and higher baseline anti-HBc levels were associated with a reduced risk of HBsAg-RS. Moreover, a significant linear dose-response relationship was observed between anti-HBs levels and the risk of HBsAg-RS after HBsAg loss. Conclusions These results provide valuable insights for predicting responses to Peg-IFN-αtherapy and identifying high-risk groups for HBsAg-RS following HBsAg loss. This information may help refine strategies for achieving and maintaining HBsAg loss and guide post-HBsAg loss monitoring and management procedures.
Xu et al. (Wed,) studied this question.