Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFNα treated patients of chronic hepatitis B
HighlightsApproximately 20% of patients with CHB who have just achieved HBsAg loss under IFNα treatment show positive serum HBV DNA and/or HBeAg.During disease progression, in frame indel mutations accumulate in the HBV genome's SP1 and SP2 promoters, with epigenetic modifications contributing to their suppression.In frame indel mutations in the HBV genome's SP1 and SP2 promoters inhibit the transcription of HBV S mRNA and promote the transcription of 3.5 kb HBV RNA.The loss of L-HBs and envelop proteins leads to an increase in intracellular cccDNA, promoting the maintenance of chronic infection.
Authors
- Bei Jiang (ORCID: https://orcid.org/0000-0002-4036-0735)
- Yuchen Xia (ORCID: https://orcid.org/0000-0001-8460-3893)
- Yifei Guo (ORCID: https://orcid.org/0000-0003-3424-8023)
- Kaitao Zhao (ORCID: https://orcid.org/0000-0002-0261-1599)
- Man‐Fung Yuen (ORCID: https://orcid.org/0000-0001-7985-7725)
- Lin Wang (ORCID: https://orcid.org/0000-0002-5478-0212)
- Fengmin Lu (ORCID: https://orcid.org/0000-0002-1832-3209)
- Minghui Li (ORCID: https://orcid.org/0000-0003-3233-5473)
- Weilin Gu (ORCID: https://orcid.org/0009-0006-1484-2622)
- Jiming Zhang (ORCID: https://orcid.org/0000-0002-6225-6381)
- Zhiqiang Gu (ORCID: https://orcid.org/0000-0002-1941-5949)
- Zhenhuan Cao (ORCID: https://orcid.org/0000-0002-6522-0093)
- Guiwen Guan (ORCID: https://orcid.org/0009-0006-3688-6829)
- Xiangmei Chen
Institutions
- Shanghai Medical College of Fudan University (CN)
- Capital University (US)
- Capital Medical University (CN)
- Peking University (CN)
- Fudan University (CN)
- Queen Mary Hospital (CN)
- Wuhan University (CN)
- Wuhan Institute of Virology (CN)
- Tianjin People's Hospital (CN)
- Xian Yang Central Hospital (CN)
- Beijing YouAn Hospital (CN)
- Taishan Medical University (CN)
- Huashan Hospital (CN)
- Shenzhen Blood Center (CN)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- State Key Laboratory of Virology
- University of Hong Kong (HK)
Publication Details
- Journal
- Emerging Microbes & Infections
- Published
- 2025-03-04
- DOI
- https://doi.org/10.1080/22221751.2025.2475847
- Citations
- 6
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 8.13
Funders
- National Natural Science Foundation of China