{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:40:06Z","timestamp":1792777206143,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2309100"],"award-info":[{"award-number":["2023YFC2309100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>HBeAg\u2010positive chronic hepatitis B (CHB) with low HBsAg levels represents a relatively rare serological pattern and is closely associated with the severity of liver disease. However, the underlying mechanisms in such cases remain largely unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Treatment\u2010na\u00efve HBeAg\u2010positive CHB patients with low HBsAg levels in China were enrolled and analysed. In\u00a0vitro cell experiments and immunoassays were conducted to investigate the effects of the preS2 deletion mutation on virus reproduction and host immune response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment\u2010na\u00efve HBeAg\u2010positive CHB patients with low HBsAg levels (low HBsAg group) exhibited higher fibrosis scores and a greater prevalence of quasispecies mutations introduced by preS2 deletion compared to patients with positive HBeAg and high HBsAg levels (high HBsAg group). Further analysis revealed that fibrosis scores in CHB patients with the preS2 deletion mutations were significantly higher compared to both in wild\u2010type patients and the high HBsAg group. In\u00a0vitro assays indicated that while this mutation may not impact HBV replication, it significantly reduced viral infectivity. The number of viral\u2010specific IFN\u2010\u03b3\u2010secreting cells induced by the mutant was significantly lower than that induced by the wild\u2010type strain. Additionally, the levels of HBs\u2010specific B cells and cytokine secretion from lymphocytes triggered by the mutant strain were significantly reduced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HBeAg\u2010positive CHB patients with low HBsAg and genotype C exhibited higher noninvasive fibrosis indexes compared with typical patients, accompanied by a significant increase in quasispecies variants associated with preS2 deletion. The emergence of the preS2 deletion mutants in patients could be due to its enhanced ability to evade the host immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.18448","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T23:54:21Z","timestamp":1734566061000},"page":"814-823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Virological and Immunological Characteristics of\n                    <scp>HBeAg<\/scp>\n                    \u2010Positive Chronic Hepatitis B Patients With Low\n                    <scp>HBsAg<\/scp>\n                    Levels"],"prefix":"10.1111","volume":"61","author":[{"given":"Yuxin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Institute of Viruses and Infectious Diseases Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Viruses and Infectious Diseases Nanjing University  Nanjing China"},{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-7960","authenticated-orcid":false,"given":"Rui","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Viruses and Infectious Diseases Nanjing University  Nanjing China"},{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Department of Infectious Diseases Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1657-010X","authenticated-orcid":false,"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Viruses and Infectious Diseases Nanjing University  Nanjing China"},{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Department of Infectious Diseases Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8420-7302","authenticated-orcid":false,"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01468-4"},{"issue":"67","key":"e_1_2_9_3_1","first-page":"370","article-title":"Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection","volume":"2017","author":"Liver EAftSot. 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