Effect of pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment HBsAg load for the seroclearance of HBsAg


Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA < 5.0 log copies/mL and without nucleot(s)ide analogs. Four HBsAg-positive cases became HBsAg negative. The HBsAg levels of the 4 patients who achieved HBsAg seroclearance were lower significantly than that of the non-seroclearance group (p = 0.007). The mean HBsAg levels in these 4 cases were 68 IU/mL, while the mean HBsAg levels in the non-seroclearance group were 2,114 IU/mL. The mean HBV-DNA levels in the 4 HBsAg seroclearance cases were 2.8 log copies/mL as compared to 3.6 log copies/mL in HBsAg-non-seroclearance cases (p = 0.01). Cases that are HBeAg negative, with HBV-DNA levels < 5 log copies/mL, and HBsAg titers < 120 IU/mL cases may achieve HBsAg clearance with Peg-IFN therapy.

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We thank the technical assistants of the Department of Gastroenterology, Kagawa University.


This research was not directly funded.

Author information




SM: Conceptualization, formal analysis, writing—original draft. KF: Investigation, methodology. KT: Investigation. MN: Investigation. KO: Investigation. TT: Investigation. HK: Investigation. JT: Investigation. AM: Investigation. TH: Supervision. TM: Conceptualization, writing—review and editing, supervision, project administration.

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Correspondence to Shima Mimura.

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Ethical approval for this study was obtained from ethical committee of Kagawa University, Japan.

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All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Mimura, S., Fujita, K., Takuma, K. et al. Effect of pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment HBsAg load for the seroclearance of HBsAg. Intern Emerg Med (2021). https://doi.org/10.1007/s11739-020-02622-7

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  • Peg-IFN
  • HBeAg negative
  • Chronic hepatitis B
  • HBsAg