Anti-interferon-α antibodies and HBsAg seroclearance during peginterferon-α therapy in chronic hepatitis B

AIMS/BACKGROUND: To identify predictors of hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) patients treated with Peginterferon-α (Peg-IFNα) and to assess the association between anti-interferon-α (anti-IFNα) antibody development and treatment outcomes. METHODS: CHB patients receiving Peg‑IFNα were categorized by serological response: 12-week responders (12W‑SR), 24-week responders (24W‑SR), and 24-week non‑responders (24W‑NSR). Independent predictors were determined using multivariate logistic regression, and the relationship between changes in anti-IFNα antibody and treatment response was analyzed. RESULTS: A total of 77 CHB patients were included: 20 (26.0%) 12W-SR, 21 (27.3%) 24W-SR, and 36 (46.8%) 24W-NSR. Lower baseline HBsAg independently predicted HBsAg clearance at week 12, while lower baseline HBsAg and younger age predicted clearance by week 24. In the 24W-NSR group, anti-IFNα IgG and IgM rose from baseline to weeks 12 and 24, with IgM increases most pronounced, whereas antibody titers remained stable in responder groups. At week 24, anti-IFNα IgM showed a modest positive correlation with HBsAg and a moderate negative correlation with hepatitis B surface antibody. CONCLUSION: CHB patients with lower baseline HBsAg or younger age achieved higher HBsAg clearance within 24 weeks. An early and pronounced rise in anti-IFNα IgM was associated with poor response to Peg-IFNα and may serve as an early warning marker.