{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:34:21Z","timestamp":1770748461026,"version":"3.50.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3\u2009years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A\/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA\u2009&amp;gt;\u20091\u2009\u00d7\u200910<jats:sup>3<\/jats:sup>\u2009IU\/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).<\/jats:p>","DOI":"10.3389\/fmicb.2022.865124","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T13:10:35Z","timestamp":1646917835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Chunyan","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renxiang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianji","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1053\/jhep.2000.19618","article-title":"Reversion from precore\/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy","volume":"32","author":"Cho","year":"2000","journal-title":"Hepatology"},{"key":"ref2","article-title":"Occult hepatitis B virus (HBV) infection and challenges for hepatitis elimination: a literature review","volume-title":"J. Appl. Microbiol.","author":"de Almeida","year":"2021"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s11262-021-01850-z","article-title":"Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina","volume":"57","author":"Delfino","year":"2021","journal-title":"Virus Genes"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.cca.2014.09.007","article-title":"Occult hepatitis B virus infection with positive hepatitis B e antigen","volume":"438","author":"Han","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1007\/s00261-021-03343-x","article-title":"Contrast-enhanced US diagnostic algorithm of hepatocellular carcinoma in patients with occult hepatitis B","volume":"47","author":"Huang","year":"2022","journal-title":"Abdom. Radiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.3390\/v13102053","article-title":"Molecular and serological characterization of hepatitis B virus (HBV)-positive samples with very low or undetectable levels of HBV surface antigen","volume":"13","author":"Kuhns","year":"2021","journal-title":"Viruses"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.3389\/fmicb.2020.01653","article-title":"Differences in HBV replication, APOBEC3 family expression, and inflammatory cytokine levels between wild-type HBV and pre-core (G1896A) or basal core promoter (A1762T\/G1764A) mutants","volume":"11","author":"Lau","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.jhep.2020.05.042","article-title":"Occult hepatitis B infection and hepatocellular carcinoma: epidemiology, virology, hepatocarcinogenesis and clinical significance","volume":"73","author":"Mak","year":"2020","journal-title":"J. Hepatol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.3390\/jcm10215201","article-title":"Risk and prevention of hepatitis B virus reactivation during immunosuppression for non-oncological diseases","volume":"10","author":"Onorato","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.4254\/wjh.v7.i7.954","article-title":"Hepatitis B reactivation in the setting of chemotherapy and immunosuppression\u2014prevention is better than cure","volume":"7","author":"Pattullo","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3466","DOI":"10.3748\/wjg.v27.i24.3466","article-title":"Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: current insights and advancements","volume":"27","author":"Perisetti","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.jhep.2019.03.034","article-title":"Update of the statements on biology and clinical impact of occult hepatitis B virus infection","volume":"71","author":"Raimondo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"5769","DOI":"10.12998\/wjcc.v9.i21.5769","article-title":"Prevention of hepatitis B reactivation in patients requiring chemotherapy and immunosuppressive therapy","volume":"9","author":"Shih","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"664833","DOI":"10.3389\/fmicb.2021.664833","article-title":"E2 site mutations in S protein strongly affect hepatitis B surface antigen detection in the occult hepatitis B virus","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.jcv.2009.09.012","article-title":"A novel hepatitis B virus mutant coexisting with wild type virus in a carrier with negative HBsAg yet positive HBeAg and anti-HBs","volume":"46","author":"Zhou","year":"2009","journal-title":"J. Clin. Virol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.865124\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T13:10:38Z","timestamp":1646917838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.865124\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":16,"alternative-id":["10.3389\/fmicb.2022.865124"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.865124","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]},"article-number":"865124"}}