{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:41:49Z","timestamp":1792489309194,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against\u00a0nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study\u2019s cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238\/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% <jats:italic>vs<\/jats:italic>. 48.1%, <jats:italic>P<\/jats:italic>\u2009=\u20090.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.<\/jats:p>","DOI":"10.1038\/s41598-019-44604-6","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T10:02:41Z","timestamp":1559210561000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection"],"prefix":"10.1038","volume":"9","author":[{"given":"Xiaoman","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-7244","authenticated-orcid":false,"given":"Meijuan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liguan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengju","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,30]]},"reference":[{"key":"44604_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jhep.2012.02.010","volume":"57","author":"European Association for the Study of the Liver","year":"2012","unstructured":"European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 57, 167\u2013185 (2012).","journal-title":"J Hepatol."},{"key":"44604_CR2","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/S0140-6736(15)61412-X","volume":"386","author":"A Schweitzer","year":"2015","unstructured":"Schweitzer, A., Horn, J., Mikolajczyk, R. T., Krause, G. & Ott, J. J. Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013. Lancet. 386, 1546\u20131555 (2015).","journal-title":"Lancet."},{"key":"44604_CR3","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","volume":"380","author":"R Lozano","year":"2012","unstructured":"Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990and 2010: A systematic analysis for the Global Burden of Disease Study2010. Lancet. 380, 2095\u20132128 (2012).","journal-title":"Lancet."},{"key":"44604_CR4","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/j.vaccine.2011.12.116","volume":"30","author":"JJ Ott","year":"2012","unstructured":"Ott, J. J., Stevens, G. A., Groeger, J. & Wiersma, S. T. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 30, 2212\u20132219 (2012).","journal-title":"Vaccine."},{"key":"44604_CR5","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.jhep.2010.06.031","volume":"54","author":"J Fung","year":"2011","unstructured":"Fung, J. et al. Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: implications for antiviral therapy. Journal of Hepatology. 54, 195\u2013200 (2011).","journal-title":"Journal of Hepatology."},{"key":"44604_CR6","doi-asserted-by":"publisher","first-page":"476","DOI":"10.7883\/yoken.65.476","volume":"65","author":"YH Shi","year":"2012","unstructured":"Shi, Y. H. Correlation between hepatitis B virus genotypes and clinical outcomes. Jpn J Infect Dis. 65, 476\u2013482 (2012).","journal-title":"Jpn J Infect Dis."},{"key":"44604_CR7","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","volume":"67","author":"European Association for the Study of the Liver","year":"2017","unstructured":"European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 67, 370\u2013398 (2017).","journal-title":"J Hepatol."},{"key":"44604_CR8","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1002\/hep.24498","volume":"54","author":"E Ridruejo","year":"2011","unstructured":"Ridruejo, E., Adrover, R. & Silva, M. O. Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. Hepatology. 54, 1104\u20131105 (2011).","journal-title":"Hepatology."},{"key":"44604_CR9","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/hep.21698","volume":"46","author":"AS Lok","year":"2007","unstructured":"Lok, A. S. et al. Antiviral drug-resistant HBV: Standardization of nomenclature and assays and recommendations for management. Hepatology. 46, 254\u2013265 (2007).","journal-title":"Hepatology."},{"key":"44604_CR10","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1093\/jac\/dkn014","volume":"61","author":"J Sheldon","year":"2008","unstructured":"Sheldon, J. & Soriano, V. Hepatitis B virus escape mutants induced by antiviral therapy. J Antimicrob Chemother. 61, 766\u2013768 (2008).","journal-title":"J Antimicrob Chemother."},{"key":"44604_CR11","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s12072-008-9048-3","volume":"2","author":"S Locarnini","year":"2008","unstructured":"Locarnini, S. Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure. Hepatol Int. 2, 147\u2013151 (2008).","journal-title":"Hepatol Int."},{"key":"44604_CR12","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.antiviral.2009.12.006","volume":"85","author":"BM Liu","year":"2010","unstructured":"Liu, B. M. et al. Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naive Chinese patients. Antivir Res. 85, 512\u2013519 (2010).","journal-title":"Antivir Res."},{"key":"44604_CR13","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1111\/j.1872-034X.2011.00873.x","volume":"41","author":"L Deng","year":"2011","unstructured":"Deng, L. & Tang, H. Hepatitis B virus drug resistance to current nucleos(t)ideanalogs: Mechanisms and mutation sites. Hepatol Res. 41, 1017\u20131024 (2011).","journal-title":"Hepatol Res."},{"key":"44604_CR14","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.3851\/IMP1677","volume":"15","author":"JX Yang","year":"2010","unstructured":"Yang, J. X. et al. Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside\/nucleotide analogue treatment among Chinese chronic hepatitis B patients. Antivir Ther. 15, 1171\u20131178 (2010).","journal-title":"Antivir Ther."},{"key":"44604_CR15","doi-asserted-by":"publisher","first-page":"11833","DOI":"10.1128\/JVI.77.21.11833-11841.2003","volume":"77","author":"WE Delaney","year":"2003","unstructured":"Delaney, W. E. et al. The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol. 77, 11833\u201311841 (2003).","journal-title":"J Virol."},{"key":"44604_CR16","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1111\/j.1440-1746.2011.06853.x","volume":"27","author":"YS Lee","year":"2012","unstructured":"Lee, Y. S. et al. rtL180M mutation of hepatitis B virus is closely associated with frequent virological resistance to adefovir dipivoxil therapy. J Gastroenterol Hepatol. 27, 300\u2013305 (2012).","journal-title":"J Gastroenterol Hepatol."},{"key":"44604_CR17","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.antiviral.2017.03.008","volume":"143","author":"D Vincenti","year":"2017","unstructured":"Vincenti, D. et al. Evolutionary trends of resistance mutational patterns of HBV reverse transcriptase over years (2002-2012) of different treatment regimens: The legacy of lamivudine\/adefovir combination treatment. Antiviral Res. 143, 62\u201368 (2017).","journal-title":"Antiviral Res."},{"key":"44604_CR18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/(SICI)1096-9071(200005)61:1<23::AID-JMV4>3.0.CO;2-X","volume":"61","author":"R Yuasa","year":"2000","unstructured":"Yuasa, R. et al. Properties of hepatitis B virus genome recovered from Vietnamese patients with fulminant hepatitis in comparison with those of acute hepatitis. J Med Virol. 61, 23\u201328 (2000).","journal-title":"J Med Virol."},{"key":"44604_CR19","doi-asserted-by":"publisher","first-page":"5837","DOI":"10.1128\/JCM.42.12.5837-5841.2004","volume":"42","author":"KL Karin","year":"2004","unstructured":"Karin, K. L., Myhre, E. & Blackberg, J. Clinical and serologicl variation between patients infected with different hepatitis B virus genotypes. J Clin Microbiol. 42, 5837\u20135841 (2004).","journal-title":"J Clin Microbiol."},{"key":"44604_CR20","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1128\/JCM.40.4.1207-1209.2002","volume":"40","author":"J Kao","year":"2002","unstructured":"Kao, J., Chen, P., Lai, M. & Chen, D. S. Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol. 40, 1207\u20131209 (2002).","journal-title":"J Clin Microbiol."},{"key":"44604_CR21","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1128\/JCM.01681-07","volume":"46","author":"M Lusida","year":"2008","unstructured":"Lusida, M. et al. Novel subtypes of hepatitis B virus genotypes C and D in Papua, Indonesia. J Clin Microbiol. 46, 2160\u20132166 (2008).","journal-title":"J Clin Microbiol."},{"key":"44604_CR22","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/j.1365-2893.2010.01301.x","volume":"18","author":"J Inoue","year":"2011","unstructured":"Inoue, J. et al. Four year study of lamivudine and adefovir combination therapy in lamivudine resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern. J Viral Hepat. 18, 206\u2013215 (2011).","journal-title":"J Viral Hepat."},{"key":"44604_CR23","first-page":"166","volume":"6","author":"J Ma","year":"2007","unstructured":"Ma, J. et al. Relationship between HBV genotypes and antiviral therapeutic efficacy of interferon-alpha. Hepatobiliary Pancreat Dis Int. 6, 166\u2013171 (2007).","journal-title":"Hepatobiliary Pancreat Dis Int."},{"key":"44604_CR24","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1053\/jhep.2001.22166","volume":"33","author":"LJ Stuyver","year":"2001","unstructured":"Stuyver, L. J. et al. Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology. 33, 751\u2013757 (2001).","journal-title":"Hepatology."},{"key":"44604_CR25","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.jhep.2007.06.011","volume":"47","author":"K Borroto-Esoda","year":"2007","unstructured":"Borroto-Esoda, K., Miller, M. D. & Arterburn, S. Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials. J Hepatol. 47, 492\u2013498 (2007).","journal-title":"J Hepatol."},{"key":"44604_CR26","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.1365-2893.2005.00657.x","volume":"12","author":"G Zeng","year":"2005","unstructured":"Zeng, G. et al. Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. J Viral Hepat. 12, 609\u2013617 (2005).","journal-title":"J Viral Hepat."},{"key":"44604_CR27","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/1743-422X-11-101","volume":"11","author":"X Chen","year":"2014","unstructured":"Chen, X. et al. A description of the hepatitis B virus genomic background in a high-prevalence area in China. Virol J. 11, 101 (2014).","journal-title":"Virol J."},{"issue":"6","key":"44604_CR28","first-page":"9630","volume":"8","author":"X He","year":"2015","unstructured":"He, X., Wang, F., Huang, B., Chen, P. & Zhong, L. Detection and analysis of resistance mutations of hepatitis B virus. Int J Clin Exp Med. 8(6), 9630\u20139639 (2015).","journal-title":"Int J Clin Exp Med."},{"issue":"1","key":"44604_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s11262-017-1518-z","volume":"54","author":"HY Zhang","year":"2018","unstructured":"Zhang, H. Y. et al. Evolution of drug-resistant mutations in HBV genomes in patients with treatment failure during the past seven years (2010-2016). Virus Genes. 54(1), 41\u201347 (2018).","journal-title":"Virus Genes."},{"key":"44604_CR30","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1111\/j.1365-2893.2010.01360.x","volume":"18","author":"Y Liu","year":"2011","unstructured":"Liu, Y. et al. Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection. J Viral Hepat. 18, e29\u2013e39 (2011).","journal-title":"J Viral Hepat."},{"key":"44604_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1002\/jmv.23182","volume":"84","author":"XG Li","year":"2012","unstructured":"Li, X. G. et al. Discrepancy of potential antiviral resistance mutation profiles within the HBV reverse transcriptase between nucleos(t)ide analogue-untreated and -treated patients with chronic hepatitis B in a hospital in China. J Med Virol. 84, 207\u2013216 (2012).","journal-title":"J Med Virol."},{"key":"44604_CR32","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/1743-422X-10-313","volume":"10","author":"J Lei","year":"2013","unstructured":"Lei, J. et al. Profile of hepatitis B virus resistance mutations against nucleoside\/nucleotide analogue treatment in Chinese patients with chronic hepatitis B. Virol J. 10, 313 (2013).","journal-title":"Virol J."},{"key":"44604_CR33","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.ijantimicag.2018.04.002","volume":"52","author":"X Guo","year":"2018","unstructured":"Guo, X. et al. Trends in hepatitis B virus resistance to nucleoside\/nucleotide analogues in North China from 2009-2016: A retrospective study. Int J Antimicrob Agents. 52, 201\u2013209 (2018).","journal-title":"Int J Antimicrob Agents."},{"key":"44604_CR34","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1053\/jhep.2002.34740","volume":"36","author":"H Yang","year":"2002","unstructured":"Yang, H. et al. Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks. Hepatology. 36, 464\u2013743 (2002).","journal-title":"Hepatology."},{"key":"44604_CR35","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1128\/JCM.43.5.2503-2505.2005","volume":"43","author":"B Z\u00f6llner","year":"2005","unstructured":"Z\u00f6llner, B. et al. Prevalence, incidence, and clinical relevance of the reverse transcriptase V207I mutation outside the YMDD motif of the hepatitis B virus polymerase during lamivudine therapy. J Clin Microbiol. 43, 2503\u20132505 (2005).","journal-title":"J Clin Microbiol."},{"key":"44604_CR36","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1111\/j.1365-2893.2005.00713.x","volume":"13","author":"J Sheldon","year":"2006","unstructured":"Sheldon, J., Rod\u00e8s, B., Zoulim, F., Bartholomeusz, A. & Soriano, V. Mutations affecting the replication capacity of the hepatitis B virus. J Viral Hepat. 13, 427\u2013434 (2006).","journal-title":"J Viral Hepat."},{"key":"44604_CR37","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/hep.510310132","volume":"31","author":"X Xiong","year":"2000","unstructured":"Xiong, X., Yang, H., Westland, C. E., Zou, R. & Gibbs, C. S. In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance. Hepatology. 31, 219\u2013224 (2000).","journal-title":"Hepatology."},{"key":"44604_CR38","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.antiviral.2012.09.014","volume":"96","author":"S Mirandola","year":"2012","unstructured":"Mirandola, S. et al. Genotype-specific mutations in the polymerase gene of hepatitis B virus potentially associated with resistance to oral antiviral therapy. Antiviral Res. 96, 422\u2013429 (2012).","journal-title":"Antiviral Res."},{"key":"44604_CR39","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.jcv.2014.03.018","volume":"60","author":"HW Lee","year":"2014","unstructured":"Lee, H. W., Chang, H. Y., Yang, S. Y. & Kim, H. J. Viral evolutionary changes during tenofovir treatment in a chronic hepatitis B patient with sequential nucleos(t)ide therapy. J Clin Virol. 60, 313\u2013316 (2014).","journal-title":"J Clin Virol."},{"key":"44604_CR40","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jcv.2012.02.003","volume":"54","author":"D Ji","year":"2012","unstructured":"Ji, D. et al. The rtL229 substitutions in the reverse transcriptase region of hepatitis B virus (HBV) polymerase are potentially associated with lamivudine resistance as a compensatory mutation. J Clin Virol. 54, 66\u201372 (2012).","journal-title":"J Clin Virol."},{"key":"44604_CR41","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1128\/JVI.02066-09","volume":"84","author":"SY Kwon","year":"2010","unstructured":"Kwon, S. Y. et al. Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients. J Virol. 84, 4494\u20134503 (2010).","journal-title":"J Virol."},{"key":"44604_CR42","doi-asserted-by":"publisher","first-page":"9678","DOI":"10.3892\/mmr.2017.7778","volume":"16","author":"B Qin","year":"2017","unstructured":"Qin, B. et al. Substitutions of rtL228 and\/or L229 are involved in the regulation of replication and HBsAg secretion in hepatitis B virus, and do not affect susceptibility to nucleos(t)ide analogs. Mol Med Rep. 16, 9678\u20139684 (2017).","journal-title":"Mol Med Rep."},{"key":"44604_CR43","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1111\/j.1365-2893.2008.00966.x","volume":"15","author":"A Gallego","year":"2008","unstructured":"Gallego, A. et al. Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B. J Viral Hepat. 15, 392\u2013398 (2008).","journal-title":"J Viral Hepat."},{"key":"44604_CR44","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1053\/j.gastro.2007.02.039","volume":"132","author":"M Ghany","year":"2007","unstructured":"Ghany, M. & Liang, T. J. Drug targets and molecular mechanisms of drug resistance in chronic hepatitis B. Gastroenterology. 132, 1574\u20131585 (2007).","journal-title":"Gastroenterology."},{"issue":"9","key":"44604_CR45","doi-asserted-by":"publisher","first-page":"4494","DOI":"10.1128\/JVI.02066-09","volume":"84","author":"SY Kwon","year":"2010","unstructured":"Kwon, S. Y. et al. Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients. J Virol. 84(9), 4494\u20134503 (2010).","journal-title":"J Virol."},{"key":"44604_CR46","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/hep4.1022","volume":"1","author":"N Yamada","year":"2017","unstructured":"Yamada, N. et al. Resistance mutations of hepatitis B virus in entecavir-refractory patients. Hepatol Commun. 1, 110\u2013121 (2017).","journal-title":"Hepatol Commun."},{"key":"44604_CR47","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.antiviral.2011.11.012","volume":"93","author":"Y Zhong","year":"2012","unstructured":"Zhong, Y. et al. Prevalence, virology and antiviral drugs susceptibility of hepatitis B virus rtN238H polymerase mutation from 1865 Chinese patients with chronic hepatitis B. Antiviral Res. 93, 185\u2013190 (2012).","journal-title":"Antiviral Res."},{"key":"44604_CR48","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1177\/135965350501000612","volume":"10","author":"J Sheldon","year":"2005","unstructured":"Sheldon, J. et al. Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir. Antivir Ther. 10, 727\u2013734 (2005).","journal-title":"Antivir Ther."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44604-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44604-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44604-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T09:55:44Z","timestamp":1671270944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44604-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,30]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["44604"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-44604-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,30]]},"assertion":[{"value":"17 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8078"}}