{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:38:22Z","timestamp":1787701102334,"version":"build-2784847793"},"reference-count":12,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Hepatitis B flare has been interpreted as result of immune response against upsurging hepatitis B virus (HBV) and its antigen(s) that may lead to HBV decline\/clearance spontaneously. It has been speculated that antiviral therapy could halt the effective immune response with viral persistent as a consequence. A proof\u2010of\u2010concept study was conducted to investigate this issue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serial biochemical, quantitative hepatitis B surface antigen (HBsAg), interferon\u2010\u03b3 (IFN\u2010\u03b3) and tumor\u2010necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) assays were performed in four patients with severe hepatitis flare who had achieved precipitous HBsAg decline within 4\u00a0weeks of antiviral therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TNF\u2010\u03b1 and IFN\u2010\u03b3 were found to be elevated in parallel to upsurging HBV DNA and HBsAg levels in all patients. Higher levels of TNF\u2010\u03b1 and IFN\u2010\u03b3 and levels relative to qHBsAg were observed during and after early termination of therapy within 4\u00a0weeks in two patients and were followed by further HBsAg decline to &lt;5 IU\/ml and even achieved HBsAg loss in one patient. The patient who had stopped therapy on day 44 showed minimal HBsAg decline afterward and the patient who continued therapy showed a 10\u2010fold rebound of qHBsAg from its nadir. The subsequent IFN\u2010\u03b3 and TNF\u2010\u03b1 activity of these two patients was minimal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results suggest that patients with severe hepatitis flare who achieved precipitous HBsAg decline may have robust immune response to clear the virus, and early termination of antiviral therapy may allow the protective immune response to continue and accelerate HBV decline toward HBsAg loss.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13804","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T15:09:07Z","timestamp":1655564947000},"page":"817-823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Robust antiviral responses in severe hepatitis flare persist after early retreatment cessation and lead toward hepatitis B surface antigen loss: A proof\u2010of\u2010concept study"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-4401","authenticated-orcid":false,"given":"Ming\u2010Ling","family":"Chang","sequence":"first","affiliation":[{"name":"Liver Research Unit Chang Gung Memorial Hospital Chang Gung University College of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4695","authenticated-orcid":false,"given":"Rong\u2010Nan","family":"Chien","sequence":"additional","affiliation":[{"name":"Liver Research Unit Chang Gung Memorial Hospital Chang Gung University College of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-9372","authenticated-orcid":false,"given":"Yun\u2010Fan","family":"Liaw","sequence":"additional","affiliation":[{"name":"Liver Research Unit Chang Gung Memorial Hospital Chang Gung University College of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.08.033"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/323819a0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.024"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031552"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.09.026"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100196\u20109"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.03.066"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31525"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab360"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13253"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010019\u20100197\u20108"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14020434"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hepr.13804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:10:31Z","timestamp":1692655831000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.13804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":12,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/hepr.13804"],"URL":"https:\/\/doi.org\/10.1111\/hepr.13804","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]},"assertion":[{"value":"2022-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}