{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:11:41Z","timestamp":1768518701611,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Serum hepatitis B virus (HBV) RNA is a new serological indicator reflecting viral replication with good clinical application prospects. This study aimed to clarify the dynamic changes of serum HBV RNA levels and the quasispecies of HBV RNA virus\u2010like particles in nucleos(t)ide analogues (NAs)\u2010experienced chronic hepatitis B (CHB) patients harboring NAs\u2010resistant mutations and their identifiable effects on NAs resistance. We included CHB patients who were on long\u2010term NAs treatment and with HBV DNA rebound. The longitudinally dynamics of serum HBV RNA levels were quantitatively detected, and the quasispecies differences between serum HBV DNA and serum HBV RNA were compared by high\u2010throughput sequencing. The effect of NAs concentration pressure on altering the resistance mutations quasispecies proportion of HBV DNA and HBV RNA in cell supernatant was analyzed in vitro. A total of 447 serum samples from 36 CHB patients treated with NAs were collected. The median follow\u2010up period was 47 months (about 4 years), and the longest follow\u2010up period was 117 months (about 10 years). Our results showed that HBV RNA could reflect virological breakthrough in 23 (64%, 23\/36) patients, and serum HBV RNA rebound earlier than HBV DNA in 12 (52%, 12\/23) patients. However, serum HBV RNA remained at a consistently high level and did not fluctuate significantly with the HBV DNA rebound in 6 of 36 patients. In addition, serum HBV RNA was not consistently detectable in 7 of the 36 patients, and their serum HBV RNA was undetectable even after HBV DNA had rebounded. The proportion of drug\u2010resistant mutations in HBV DNA was higher than that of HBV RNA by high\u2010throughput sequencing. The results of in vitro experiments showed that the viral strains with drug\u2010resistant mutation in HBV DNA in cell supernatants gradually become the dominant strains with the increase of NAs concentrations. Serum HBV RNA levels can reflect virological breakthrough in most NAs\u2010 treated CHB patients, but there are certain limitations. NAs alter the quasispecies composition of serum HBV DNA and serum HBV RNA, resulting in a higher detection rate of drug\u2010resistant mutations in serum HBV DNA than in serum HBV RNA.<\/jats:p>","DOI":"10.1002\/jmv.28612","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T09:49:05Z","timestamp":1677318545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)\u2010resistant mutations in serum HBV DNA and serum HBV RNA"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-2884","authenticated-orcid":false,"given":"Hao","family":"Liao","sequence":"first","affiliation":[{"name":"Intervention and Cell Therapy Center, Peking University Shenzhen Hospital Shenzhen Peking University\u2010The Hong Kong University of Science and Technology Medical Center Shenzhen China"},{"name":"Department of Clinical Laboratory, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Southern University of Science and Technology Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Southern University of Science and Technology Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinman","family":"Shao","sequence":"additional","affiliation":[{"name":"Comprehensive Internal Medicine Department Beijing Xiaotangshan Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Southern University of Science and Technology Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei V.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Intervention and Cell Therapy Center, Peking University Shenzhen Hospital Shenzhen Peking University\u2010The Hong Kong University of Science and Technology Medical Center Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The Fifth Medical Center of Chinese PLA General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangxin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; 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