{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:41:32Z","timestamp":1789656092634,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg\u2010IFN\u2010\u03b1) for patients with chronic hepatitis B (CHB). Eighty patients who received 48\u2010week Peg\u2010IFN\u2010\u0251 and NA combination therapy followed by Peg\u2010IFN\u2010\u0251 monotherapy for additional 48 weeks were included in this study. HBV\u2010related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg\u2010IFN\u2010\u0251 and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014). The patients with HBcrAg\u2265\u20095\u2009log\n                    <jats:sub>10<\/jats:sub>\n                    U\/mL and HBsAg\u2265\u2009100\u2009IU\/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg\u2265\u20095\u2009log\n                    <jats:sub>10<\/jats:sub>\n                    U\/mL than those with HBcrAg&lt;\u20095\u2009log\n                    <jats:sub>10<\/jats:sub>\n                    U\/mL. Notably, in contrast to patients with HBcrAg&lt;\u20095\u2009log\n                    <jats:sub>10<\/jats:sub>\n                    U\/mL or with HBsAg&lt;\u2009100\u2009IU\/mL who had obviously restored HBV\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell, Tfh or B cell responses before NA cessation, those with HBcrAg\u2265\u20095\u2009log\n                    <jats:sub>10<\/jats:sub>\n                    U\/mL or with HBsAg\u2265\u2009100\u2009IU\/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg\u2010IFN\u2010\u0251 strategy, may help to avoid VBT and improve functional cure of CHB.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70021","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T04:36:56Z","timestamp":1731386216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["HBV Antigen\u2010Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure"],"prefix":"10.1002","volume":"96","author":[{"given":"Da","family":"Huang","sequence":"first","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhize","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-9593","authenticated-orcid":false,"given":"Qin","family":"Ning","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Yan","sequence":"additional","affiliation":[{"name":"Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China"},{"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-015-9675-4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.039"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-020-10099-x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13283"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14629"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","unstructured":"S. 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