{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:32:09Z","timestamp":1791106329519,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T00:00:00Z","timestamp":1360195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"crossref","award":["101-S1878"],"award-info":[{"award-number":["101-S1878"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"crossref","award":["NSC 100-2314-B-002-049-MY3"],"award-info":[{"award-number":["NSC 100-2314-B-002-049-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Liver Disease Prevention & Treatment Research Foundation"},{"DOI":"10.13039\/501100004866","name":"National Research Program for Biopharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004866","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Taiwan-LiverNet Consortium","award":["NSC100-2325-B-002-052"],"award-info":[{"award-number":["NSC100-2325-B-002-052"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Precore (PC) (G1896A) and basal core promoter (BCP) (A1762T\/G1764A) mutations of the hepatitis B virus (HBV) genome often emerge in chronic hepatitis B (CHB) patients. Their roles in hepatitis B e antigen (HBeAg) seroconversion induced by interferon (IFN) therapy remain controversial, partly because quantitative analysis for these mutants is lacking. This study aimed to develop a new assay to accurately quantify the PC and BCP mutant percentages and correlate their dynamic changes with IFN-induced HBeAg seroconversion in HBeAg-positive CHB patients. The PC and BCP mutant percentages were analyzed by polymerase chain reaction (PCR)-pyrosequencing. Our results showed that this quantitative assay for PC and BCP mutants achieved high accuracy (R2 &gt; 0.99) within a range between 10% and 90% mutants. We examined dynamic changes of the PC and BCP mutant percentages following IFN treatment in 203 HBeAg-positive CHB patients. By multiple logistic regression analysis, we found that the chance of HBeAg seroconversion increased by 2.2% (odds ratio [OR] = 1.022, 95% confidence interval [CI]: 1.009\u20131.034,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.001) and 2.3% (OR = 1.023, 95% CI: 1.010\u20131.037,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.001) per 1% increase of the pretreatment PC and BCP mutant percentages, respectively, after adjustment for other predictors. However, only the pretreatment PC mutation percentage was significantly associated with HBeAg seroconversion with HBV DNA &lt; 2,000 IU\/mL (OR = 1.030, 95% CI: 1.014\u20131.047,<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001). Furthermore, the mutant percentage of PC, but not BCP, in patients achieving HBeAg seroclearance with HBV DNA &lt; 20,000 IU\/mL increased significantly during IFN treatment<\/jats:bold> (<jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.039). Interestingly, patients with HBeAg seroconversion who had a high PC mutant percentage at the end of IFN treatment tended to exhibit high viremia after seroconversion.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Quantitative analysis of PC and BCP mutants can predict IFN-induced HBeAg seroconversion and demonstrate their distinct evolution patterns during HBeAg seroconversion. (Hepatology 2013)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26121","type":"journal-article","created":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T18:56:32Z","timestamp":1351623392000},"page":"934-943","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":45,"title":["Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced hepatitis B e antigen seroconversion"],"prefix":"10.1097","volume":"57","author":[{"given":"Hung-Chih","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Chi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Jen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Chung","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung-Hung","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Long","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Lung","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yen","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Jer","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-Shinn","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Horng","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-14-20241201","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1056\/NEJMra0801644","article-title":"Hepatitis B virus infection.","volume":"359","author":"Dienstag","year":"2008","journal-title":"N Engl J Med"},{"key":"R2-14-20241201","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/S0140-6736(09)60207-5","article-title":"Hepatitis B virus infection.","volume":"373","author":"Liaw","year":"2009","journal-title":"Lancet"},{"key":"R3-14-20241201","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1007\/s10620-010-1179-4","article-title":"Hepatitis B e antigen seroconversion: a critical event in chronic hepatitis B virus infection.","volume":"55","author":"Liaw","year":"2010","journal-title":"Dig Dis Sci"},{"key":"R4-14-20241201","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1056\/NEJMoa013215","article-title":"Hepatitis B e antigen and the risk of hepatocellular carcinoma.","volume":"347","author":"Yang","year":"2002","journal-title":"N Engl J Med"},{"key":"R5-14-20241201","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12072-007-9033-2","article-title":"Role of viral factors in the natural course and therapy of chronic hepatitis B.","volume":"1","author":"Kao","year":"2007","journal-title":"Hepatol Int"},{"key":"R6-14-20241201","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrgastro.2009.107","article-title":"Hepatitis B virus variants.","volume":"6","author":"Chotiyaputta","year":"2009","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"R7-14-20241201","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0065-3527(08)60298-5","article-title":"Naturally occurring variants of hepatitis B virus.","volume":"52","author":"Gunther","year":"1999","journal-title":"Adv Virus Res"},{"key":"R8-14-20241201","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/S0140-6736(89)90713-7","article-title":"Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection.","volume":"2","author":"Carman","year":"1989","journal-title":"Lancet"},{"key":"R9-14-20241201","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1053\/jhep.2003.50352","article-title":"Prevalence of HBV precorecore promoter variants in the United States.","volume":"38","author":"Chu","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R10-14-20241201","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1086\/344327","article-title":"Relationship between the development of precore and core promoter mutations and hepatitis B e antigen seroconversion in patients with chronic hepatitis B virus.","volume":"186","author":"Yuen","year":"2002","journal-title":"J Infect Dis"},{"key":"R11-14-20241201","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/JCM.40.1.16-21.2002","article-title":"Precore stop mutant in HBeAgpositive patients with chronic hepatitis B: clinical characteristics and correlation with the course of HBeAgtoantiHBe seroconversion.","volume":"40","author":"Chu","year":"2002","journal-title":"J Clin Microbiol"},{"key":"R12-14-20241201","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jhep.2011.11.012","article-title":"Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion.","volume":"56","author":"Nie","year":"2012","journal-title":"J Hepatol"},{"key":"R13-14-20241201","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jhep.2004.02.024","article-title":"Realtime quantification of hepatitis B virus corepromoter and precore mutants during hepatitis E antigen seroconversion.","volume":"40","author":"Pang","year":"2004","journal-title":"J Hepatol"},{"key":"R14-14-20241201","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/jnci\/djn243","article-title":"Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma.","volume":"100","author":"Yang","year":"2008","journal-title":"J Natl Cancer Inst"},{"key":"R15-14-20241201","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/hep.23190","article-title":"Chronic hepatitis B: update 2009.","volume":"50","author":"Lok","year":"2009","journal-title":"HEPATOLOGY"},{"key":"R16-14-20241201","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/hep.510310323","article-title":"Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B.","volume":"31","author":"Erhardt","year":"2000","journal-title":"HEPATOLOGY"},{"key":"R17-14-20241201","first-page":"1355","article-title":"Hepatitis B virus precorecore variation and interferon therapy.","volume":"22","author":"Fattovich","year":"1995","journal-title":"HEPATOLOGY"},{"key":"R18-14-20241201","first-page":"19","article-title":"Predictive value of precore hepatitis B virus mutations in spontaneous and interferoninduced hepatitis B e antigen clearance.","volume":"21","author":"Lok","year":"1995","journal-title":"HEPATOLOGY"},{"key":"R19-14-20241201","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/00004836-200405000-00013","article-title":"Response to interferonalpha in chronic hepatitis B with and without precore mutant strain detected by mutation sitespecific assay.","volume":"38","author":"Seo","year":"2004","journal-title":"J Clin Gastroenterol"},{"key":"R20-14-20241201","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3851\/IMP1841","article-title":"Effect of host and viral factors on hepatitis B e antigenpositive chronic hepatitis B patients receiving pegylated interferonalpha2a therapy.","volume":"16","author":"Tseng","year":"2011","journal-title":"Antivir Ther"},{"key":"R21-14-20241201","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jviromet.2008.07.017","article-title":"A new and rapid genotypic assay for the detection of neuraminidase inhibitor resistant influenza A viruses of subtype H1N1, H3N2, and H5N1.","volume":"153","author":"Duwe","year":"2008","journal-title":"J Virol Methods"},{"key":"R22-14-20241201","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.1128\/JCM.42.10.4788-4795.2004","article-title":"Pyrosequencing for detection of lamivudineresistant hepatitis B virus.","volume":"42","author":"Lindstrom","year":"2004","journal-title":"J Clin Microbiol"},{"key":"R23-14-20241201","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/hep.21100","article-title":"Interferon alpha2b with and without ribavirin in the treatment of hepatitis B e antigenpositive chronic hepatitis B: a randomized study.","volume":"43","author":"Liu","year":"2006","journal-title":"HEPATOLOGY"},{"key":"R24-14-20241201","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s12072-008-9080-3","article-title":"AsianPacific consensus statement on the management of chronic hepatitis B: a 2008 update.","volume":"2","author":"Liaw","year":"2008","journal-title":"Hepatol Int"},{"key":"R25-14-20241201","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/nprot.2007.244","article-title":"Pyrosequencing protocol using a universal biotinylated primer for mutation detection and SNP genotyping.","volume":"2","author":"Royo","year":"2007","journal-title":"Nat Protoc"},{"key":"R26-14-20241201","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1053\/jhep.2003.50453","article-title":"Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection.","volume":"38","author":"Milich","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R27-14-20241201","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1128\/jvi.64.3.1298-1303.1990","article-title":"Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen.","volume":"64","author":"Okamoto","year":"1990","journal-title":"J Virol"},{"key":"R28-14-20241201","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1002\/hep.1840160606","article-title":"Hepatitis B virus precore mutants are identical in carriers from various ethnic origins and are associated with a range of liver disease severity.","volume":"16","author":"TurKaspa","year":"1992","journal-title":"HEPATOLOGY"},{"key":"R29-14-20241201","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/hep.24555","article-title":"Shorter durations and lower doses of peginterferon alfa2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.","volume":"54","author":"Liaw","year":"2011","journal-title":"HEPATOLOGY"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26121","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201303000-00014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T14:07:25Z","timestamp":1733062045000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201303000-00014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26121","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2013,3]]}}}