{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:38:23Z","timestamp":1792787903012,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the National Science and Technology Major Project of China","award":["2017ZX10202202-002-004"],"award-info":[{"award-number":["2017ZX10202202-002-004"]}]},{"name":"the Science and Technology Project of Chengdu","award":["2017-CY02-00018-GX"],"award-info":[{"award-number":["2017-CY02-00018-GX"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n\u2009=\u200925), a tenofovir (TDF) monotherapy group (n\u2009=\u200927), and an ETV and TDF combination therapy group (n\u2009=\u200920). Virologic, biochemical, and serologic responses were compared among the three groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48\u00a0weeks (74.07% vs 70.00%, P\u2009&gt;\u20090.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-021-06554-1","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T06:03:31Z","timestamp":1630908211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of different nucleoside analog rescue therapies for entecavir-resistant chronic hepatitis B patients"],"prefix":"10.1186","volume":"21","author":[{"given":"Jin","family":"Shang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rili M.","family":"Ise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiu","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"6554_CR1","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S1473-3099(16)30204-3","volume":"16","author":"S Nayagam","year":"2016","unstructured":"Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis. 2016;16:1399\u2013408.","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"6554_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12072-015-9675-4","volume":"10","author":"SK Sarin","year":"2016","unstructured":"Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1\u201398.","journal-title":"Hepatol Int"},{"issue":"1","key":"6554_CR3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/cld.728","volume":"12","author":"NA Terrault","year":"2018","unstructured":"Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Clin Liver Dis (Hoboken). 2018;12(1):33\u20134.","journal-title":"Clin Liver Dis (Hoboken)"},{"issue":"2","key":"6554_CR4","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. 2017;67(2):370\u201398.","journal-title":"J Hepatol"},{"issue":"1","key":"6554_CR5","first-page":"15","volume":"21","author":"H Zhuang","year":"2013","unstructured":"Zhuang H, Weng X. Development and management of drug resistance to nucleoside\/nucleotide analogues in patients with chronic hepatitis B. Chin J Hepatol. 2013;21(1):15\u201322.","journal-title":"Chin J Hepatol"},{"key":"6554_CR6","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1128\/AAC.00833-06","volume":"51","author":"DJ Tenney","year":"2007","unstructured":"Tenney DJ, Rose RE, Baldick CJ, et al. Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present. Antimicrob Agents Chemother. 2007;51:902\u201311.","journal-title":"Antimicrob Agents Chemother"},{"key":"6554_CR7","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1177\/135965350701200816","volume":"12","author":"MF Yuen","year":"2007","unstructured":"Yuen MF, Seto WK, Chow DH, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12:1295\u2013303.","journal-title":"Antivir Ther"},{"key":"6554_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.antiviral.2016.12.012","volume":"139","author":"Y Liu","year":"2017","unstructured":"Liu Y, Miller MD, Kitrinos KM. Tenofovir alafenamide demonstrates broad cross-genotype activity against wild-type HBV clinical isolates and maintains susceptibility to drug-resistant HBV isolates in vitro. Antivir Res. 2017;139:25\u201331.","journal-title":"Antivir Res"},{"issue":"Suppl 4","key":"6554_CR9","first-page":"314A","volume":"60","author":"F Zoulim","year":"2014","unstructured":"Zoulim F, Jablkowski MS, Diculescu M, et al. The safety and efficacy of entecavir and tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure: week 96 results of the ENTEBE study. Hepatology. 2014;60(Suppl 4):314A-315A.","journal-title":"Hepatology"},{"issue":"38","key":"6554_CR10","doi-asserted-by":"publisher","first-page":"10874","DOI":"10.3748\/wjg.v21.i38.10874","volume":"21","author":"HS Kim","year":"2015","unstructured":"Kim HS, Yim HJ, Jang MK, et al. Management of entecavir-resistant chronic hepatitis B with adefovir-based combination therapies. World J Gastroenterol. 2015;21(38):10874\u201382.","journal-title":"World J Gastroenterol"},{"key":"6554_CR11","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1002\/hep.27406","volume":"60","author":"FS Wang","year":"2014","unstructured":"Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014;60:2099\u2013108.","journal-title":"Hepatology"},{"key":"6554_CR12","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","volume":"64","author":"S Tong","year":"2016","unstructured":"Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol. 2016;64:S4-16.","journal-title":"J Hepatol"},{"issue":"Suppl 1","key":"6554_CR13","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/liv.12069","volume":"33","author":"F Zoulim","year":"2013","unstructured":"Zoulim F, Locarnini S. Optimal management of chronic hepatitis B patients with treatment failure and antiviral drug resistance. Liver Int. 2013;33(Suppl 1):116\u201324.","journal-title":"Liver Int"},{"issue":"8","key":"6554_CR14","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/jvh.12368","volume":"22","author":"L Lu","year":"2015","unstructured":"Lu L, Yip B, Trinh H, et al. Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir. J Viral Hepat. 2015;22(8):675\u201381.","journal-title":"J Viral Hepat"},{"issue":"9","key":"6554_CR15","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1016\/j.clinthera.2017.07.015","volume":"39","author":"J Chen","year":"2017","unstructured":"Chen J, Zhao SS, Liu XX, Huang ZB, Huang Y. Comparison of the efficacy of tenofovir versus tenofovir plus entecavir in the treatment of chronic hepatitis B in patients with poor efficacy of entecavir: a systematic review and meta-analysis. Clin Ther. 2017;39(9):1870\u201380.","journal-title":"Clin Ther"},{"issue":"1","key":"6554_CR16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jhep.2019.02.021","volume":"71","author":"YS Lim","year":"2019","unstructured":"Lim YS, Gwak GY, Choi J, et al. Monotherapy with tenofovir disoproxil fumarate for adefovir-resistant vs. entecavir-resistant chronic hepatitis B: a 5-year clinical trial. J Hepatol. 2019;71(1):35\u201344.","journal-title":"J Hepatol"},{"issue":"2","key":"6554_CR17","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s12223-018-0650-z","volume":"64","author":"S Alacam","year":"2019","unstructured":"Alacam S, Karabulut N, Yolcu A, et al. Evaluation of drug resistance mutations in patients with chronic hepatitis B. Folia Microbiol (Praha). 2019;64(2):237\u201343.","journal-title":"Folia Microbiol (Praha)"},{"issue":"1","key":"6554_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/liv.14241","volume":"40","author":"D Jiang","year":"2020","unstructured":"Jiang D, Wang J, Zhao X, et al. Entecavir resistance mutations rtL180M\/T184L\/M204V combined with rtA200V lead to tenofovir resistance. Liver Int. 2020;40(1):83\u201391.","journal-title":"Liver Int"},{"issue":"3","key":"6554_CR19","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/hep.29187","volume":"66","author":"YS Lim","year":"2017","unstructured":"Lim YS, Lee YS, Gwak GY, et al. Monotherapy with tenofovir disoproxil fumarate for multiple drug-resistant chronic hepatitis B: 3-year trial. Hepatology. 2017;66(3):772\u201383.","journal-title":"Hepatology"},{"issue":"1","key":"6554_CR20","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jinf.2015.09.038","volume":"72","author":"E Murakami","year":"2016","unstructured":"Murakami E, Tsuge M, Hiraga N, et al. Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones. J Infect. 2016;72(1):91\u2013102.","journal-title":"J Infect"},{"issue":"11","key":"6554_CR21","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1038\/ki.2010.318","volume":"78","author":"LC Herlitz","year":"2010","unstructured":"Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D\u2019Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int. 2010;78(11):1171\u20137.","journal-title":"Kidney Int"},{"issue":"11","key":"6554_CR22","doi-asserted-by":"publisher","first-page":"6710","DOI":"10.1128\/AAC.03845-14","volume":"58","author":"YB Lee","year":"2014","unstructured":"Lee YB, Lee JH, Lee DH, et al. Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains. Antimicrob Agents Chemother. 2014;58(11):6710\u20136.","journal-title":"Antimicrob Agents Chemother"},{"issue":"5","key":"6554_CR23","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1136\/gutjnl-2014-308353","volume":"65","author":"YS Lim","year":"2016","unstructured":"Lim YS, Byun KS, Yoo BC, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial. Gut. 2016;65(5):852\u201360.","journal-title":"Gut"},{"key":"6554_CR24","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/jmv.23567","volume":"85","author":"R Salpini","year":"2013","unstructured":"Salpini R, Alteri C, Cento V, et al. Snapshot on drugresistance rate and profiles in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. J Med Virol. 2013;85:996\u20131004.","journal-title":"J Med Virol"},{"key":"6554_CR25","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.jhep.2005.05.037","volume":"43","author":"SK Fung","year":"2005","unstructured":"Fung SK, Andreone P, Han SH, et al. Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol. 2005;43:937\u201343.","journal-title":"J Hepatol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06554-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-021-06554-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-021-06554-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T12:23:56Z","timestamp":1673180636000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-021-06554-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["6554"],"URL":"https:\/\/doi.org\/10.1186\/s12879-021-06554-1","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]},"assertion":[{"value":"21 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the ethics committee of West China Hospital at Sichuan University. All including patients from the Center of Infectious Diseases, West China Hospital signed written informed consents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare they have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"912"}}