Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy

ObjectiveTo investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures.Methods31 pat...

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Veröffentlicht in:Gut 2011-09, Vol.60 (9), p.1269-1277
Hauptverfasser: Liu, Feng, Chen, Li, Yu, De-Min, Deng, Lin, Chen, Rong, Jiang, Yin, Chen, Liang, Huang, Su-Yuan, Yu, Jia-Lun, Gong, Qi-Ming, Zhang, Xin-Xin
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container_end_page 1277
container_issue 9
container_start_page 1269
container_title Gut
container_volume 60
creator Liu, Feng
Chen, Li
Yu, De-Min
Deng, Lin
Chen, Rong
Jiang, Yin
Chen, Liang
Huang, Su-Yuan
Yu, Jia-Lun
Gong, Qi-Ming
Zhang, Xin-Xin
description ObjectiveTo investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures.Methods31 patients with chronic hepatitis B receiving entecavir (17 responders and 14 partial responders according to the HBV DNA levels at week 48) and 25 patients receiving lamivudine (14 responders and 11 non-responders) as controls were included. An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced.ResultsQS complexity and diversity, in addition to alanine aminotransferase and HBV DNA levels, were comparable between responders and partial responders at baseline. However, QS complexity in responders at week 4 was statistically lower than that in partial responders at the nucleotide level (0.6494 vs 0.7723, p=0.039). Net changes in diversity as well as the viral nucleotide substitution rate of responders were higher than those of partial responders, and both correlated with virological responses at both week 48 and the final visit (mean: 28 months). A preliminary model of QS evolution variables predicted 16 of 17 responders and 13 of 14 partial responders in the entecavir group. Despite significant differences between responders to entecavir and responders to lamivudine at week 4, the characteristics of QS were quite similar between partial responders to entecavir and non-responders to lamivudine.ConclusionsThe evolutionary patterns of HBV RT QS differ between responders and partial responders during the early stage of entecavir treatment. Characteristics of HBV QS evolution during the first 4 weeks contribute to the prediction of long-term virological responses. The similar patterns of HBV RT QS in partial responders and non-responders receiving different nucleoside analogues may imply a novel mechanism of drug resistance, which warrants further investigation.
doi_str_mv 10.1136/gut.2010.226225
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An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced.ResultsQS complexity and diversity, in addition to alanine aminotransferase and HBV DNA levels, were comparable between responders and partial responders at baseline. However, QS complexity in responders at week 4 was statistically lower than that in partial responders at the nucleotide level (0.6494 vs 0.7723, p=0.039). Net changes in diversity as well as the viral nucleotide substitution rate of responders were higher than those of partial responders, and both correlated with virological responses at both week 48 and the final visit (mean: 28 months). A preliminary model of QS evolution variables predicted 16 of 17 responders and 13 of 14 partial responders in the entecavir group. Despite significant differences between responders to entecavir and responders to lamivudine at week 4, the characteristics of QS were quite similar between partial responders to entecavir and non-responders to lamivudine.ConclusionsThe evolutionary patterns of HBV RT QS differ between responders and partial responders during the early stage of entecavir treatment. Characteristics of HBV QS evolution during the first 4 weeks contribute to the prediction of long-term virological responses. The similar patterns of HBV RT QS in partial responders and non-responders receiving different nucleoside analogues may imply a novel mechanism of drug resistance, which warrants further investigation.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2010.226225</identifier><identifier>PMID: 21292683</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Adolescent ; Adult ; Aged ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiretroviral drugs ; Antiviral agents ; Antiviral Agents - therapeutic use ; antiviral therapy ; Biological and medical sciences ; chronic/drug therapy/virology ; Clinical medicine ; Deoxyribonucleic acid ; DNA ; DNA, Viral - blood ; DNA, Viral - genetics ; Drug dosages ; Drug resistance ; Drug Resistance, Viral - genetics ; evolution ; Evolution, Molecular ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; genetic heterogeneity ; Genetic Variation ; genetics ; Guanine - analogs &amp; derivatives ; Guanine - therapeutic use ; Hepatitis ; Hepatitis B ; Hepatitis B virus ; Hepatitis B virus - classification ; Hepatitis B virus - drug effects ; Hepatitis B virus - genetics ; Hepatitis B virus - isolation &amp; purification ; hepatitis B virus/drug effects/genetics ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - virology ; Humans ; Lamivudine - therapeutic use ; Liver cirrhosis ; Liver diseases ; Male ; Medical sciences ; Middle Aged ; molecular ; Mutation ; Pharmacology. Drug treatments ; Phylogeny ; Retrospective Studies ; RNA-Directed DNA Polymerase - genetics ; Selection, Genetic ; Sequence Analysis, DNA - methods ; Studies ; Treatment Outcome ; Young Adult</subject><ispartof>Gut, 2011-09, Vol.60 (9), p.1269-1277</ispartof><rights>2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright: 2011 (c) 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b459t-b4fc555d50c3942aa76317062c8941177ac0d5830de4895f50f2cc0c19b608c53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://gut.bmj.com/content/60/9/1269.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://gut.bmj.com/content/60/9/1269.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3196,23571,27924,27925,77600,77631</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=24420104$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21292683$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Yu, De-Min</creatorcontrib><creatorcontrib>Deng, Lin</creatorcontrib><creatorcontrib>Chen, Rong</creatorcontrib><creatorcontrib>Jiang, Yin</creatorcontrib><creatorcontrib>Chen, Liang</creatorcontrib><creatorcontrib>Huang, Su-Yuan</creatorcontrib><creatorcontrib>Yu, Jia-Lun</creatorcontrib><creatorcontrib>Gong, Qi-Ming</creatorcontrib><creatorcontrib>Zhang, Xin-Xin</creatorcontrib><title>Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy</title><title>Gut</title><addtitle>Gut</addtitle><description>ObjectiveTo investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures.Methods31 patients with chronic hepatitis B receiving entecavir (17 responders and 14 partial responders according to the HBV DNA levels at week 48) and 25 patients receiving lamivudine (14 responders and 11 non-responders) as controls were included. An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced.ResultsQS complexity and diversity, in addition to alanine aminotransferase and HBV DNA levels, were comparable between responders and partial responders at baseline. However, QS complexity in responders at week 4 was statistically lower than that in partial responders at the nucleotide level (0.6494 vs 0.7723, p=0.039). Net changes in diversity as well as the viral nucleotide substitution rate of responders were higher than those of partial responders, and both correlated with virological responses at both week 48 and the final visit (mean: 28 months). A preliminary model of QS evolution variables predicted 16 of 17 responders and 13 of 14 partial responders in the entecavir group. Despite significant differences between responders to entecavir and responders to lamivudine at week 4, the characteristics of QS were quite similar between partial responders to entecavir and non-responders to lamivudine.ConclusionsThe evolutionary patterns of HBV RT QS differ between responders and partial responders during the early stage of entecavir treatment. Characteristics of HBV QS evolution during the first 4 weeks contribute to the prediction of long-term virological responses. The similar patterns of HBV RT QS in partial responders and non-responders receiving different nucleoside analogues may imply a novel mechanism of drug resistance, which warrants further investigation.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiretroviral drugs</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>antiviral therapy</subject><subject>Biological and medical sciences</subject><subject>chronic/drug therapy/virology</subject><subject>Clinical medicine</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Viral - blood</subject><subject>DNA, Viral - genetics</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance, Viral - genetics</subject><subject>evolution</subject><subject>Evolution, Molecular</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>genetic heterogeneity</subject><subject>Genetic Variation</subject><subject>genetics</subject><subject>Guanine - analogs &amp; derivatives</subject><subject>Guanine - therapeutic use</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - classification</subject><subject>Hepatitis B virus - drug effects</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - isolation &amp; purification</subject><subject>hepatitis B virus/drug effects/genetics</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Hepatitis B, Chronic - virology</subject><subject>Humans</subject><subject>Lamivudine - therapeutic use</subject><subject>Liver cirrhosis</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>molecular</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Phylogeny</subject><subject>Retrospective Studies</subject><subject>RNA-Directed DNA Polymerase - genetics</subject><subject>Selection, Genetic</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Studies</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkctv1DAQxiMEotvCmRuyhBASUlo_E7s32LaAVMGFl7hYXmdMvWST1I-F3vjTcbRLkbj0MqORf_PpG39V9YTgY0JYc_I9p2OKy0RpQ6m4Vy0Ib2TNqJT3qwXGpK1Fy9VBdRjjGmMspSIPqwNKqKKNZIvq9_l27HPy42DCDZpMShCGiEaHrqBMPvmIXqOtDzmi62yijxNYDxHloYOAOu8cBBgSitCDTX4LaAoQYy7lFNkxBOjNLI9--nSFzFAQH0yPwDlvjb15VD1wpo_weN-Pqk8X5x-Xb-vLD2_eLV9d1isuVCrVWSFEJ7BlilNj2oaRFjfUSsUJaVtjcSckwx1wqYQT2FFrsSVq1WBpBTuqXux0pzBeZ4hJb3y00PdmgDFHrTDnklKq7iSlYi1ljPJCPvuPXI85DOUMXRwpJjCTbaFOdpQNY4wBnJ6C35Tv1gTrOUVdUtRzinqXYtl4utfNqw10t_zf2ArwfA-YaE3vghmsj_84zme52WC943xM8Ov23YQfumlZK_T7z0tNv4gL_O3rmZ5Pf7njV5v1nS7_AJYswsk</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Liu, Feng</creator><creator>Chen, Li</creator><creator>Yu, De-Min</creator><creator>Deng, Lin</creator><creator>Chen, Rong</creator><creator>Jiang, Yin</creator><creator>Chen, Liang</creator><creator>Huang, Su-Yuan</creator><creator>Yu, Jia-Lun</creator><creator>Gong, Qi-Ming</creator><creator>Zhang, Xin-Xin</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7T5</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20110901</creationdate><title>Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy</title><author>Liu, Feng ; Chen, Li ; Yu, De-Min ; Deng, Lin ; Chen, Rong ; Jiang, Yin ; Chen, Liang ; Huang, Su-Yuan ; Yu, Jia-Lun ; Gong, Qi-Ming ; Zhang, Xin-Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b459t-b4fc555d50c3942aa76317062c8941177ac0d5830de4895f50f2cc0c19b608c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiretroviral drugs</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - therapeutic use</topic><topic>antiviral therapy</topic><topic>Biological and medical sciences</topic><topic>chronic/drug therapy/virology</topic><topic>Clinical medicine</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Viral - blood</topic><topic>DNA, Viral - genetics</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drug Resistance, Viral - genetics</topic><topic>evolution</topic><topic>Evolution, Molecular</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>genetic heterogeneity</topic><topic>Genetic Variation</topic><topic>genetics</topic><topic>Guanine - analogs &amp; derivatives</topic><topic>Guanine - therapeutic use</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - classification</topic><topic>Hepatitis B virus - drug effects</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - isolation &amp; purification</topic><topic>hepatitis B virus/drug effects/genetics</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatitis B, Chronic - virology</topic><topic>Humans</topic><topic>Lamivudine - therapeutic use</topic><topic>Liver cirrhosis</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>molecular</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Phylogeny</topic><topic>Retrospective Studies</topic><topic>RNA-Directed DNA Polymerase - genetics</topic><topic>Selection, Genetic</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Studies</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Feng</creatorcontrib><creatorcontrib>Chen, Li</creatorcontrib><creatorcontrib>Yu, De-Min</creatorcontrib><creatorcontrib>Deng, Lin</creatorcontrib><creatorcontrib>Chen, Rong</creatorcontrib><creatorcontrib>Jiang, Yin</creatorcontrib><creatorcontrib>Chen, Liang</creatorcontrib><creatorcontrib>Huang, Su-Yuan</creatorcontrib><creatorcontrib>Yu, Jia-Lun</creatorcontrib><creatorcontrib>Gong, Qi-Ming</creatorcontrib><creatorcontrib>Zhang, Xin-Xin</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Feng</au><au>Chen, Li</au><au>Yu, De-Min</au><au>Deng, Lin</au><au>Chen, Rong</au><au>Jiang, Yin</au><au>Chen, Liang</au><au>Huang, Su-Yuan</au><au>Yu, Jia-Lun</au><au>Gong, Qi-Ming</au><au>Zhang, Xin-Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>60</volume><issue>9</issue><spage>1269</spage><epage>1277</epage><pages>1269-1277</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>ObjectiveTo investigate the evolution of hepatitis B virus (HBV) quasispecies (QS) within the reverse transcriptase (RT) region during the early stage of entecavir treatment and its impact on virological response, and to compare evolutionary patterns under different selective pressures.Methods31 patients with chronic hepatitis B receiving entecavir (17 responders and 14 partial responders according to the HBV DNA levels at week 48) and 25 patients receiving lamivudine (14 responders and 11 non-responders) as controls were included. An average of 26 clones (2892 total from both groups) spanning the RT region per sample was sequenced.ResultsQS complexity and diversity, in addition to alanine aminotransferase and HBV DNA levels, were comparable between responders and partial responders at baseline. However, QS complexity in responders at week 4 was statistically lower than that in partial responders at the nucleotide level (0.6494 vs 0.7723, p=0.039). Net changes in diversity as well as the viral nucleotide substitution rate of responders were higher than those of partial responders, and both correlated with virological responses at both week 48 and the final visit (mean: 28 months). A preliminary model of QS evolution variables predicted 16 of 17 responders and 13 of 14 partial responders in the entecavir group. Despite significant differences between responders to entecavir and responders to lamivudine at week 4, the characteristics of QS were quite similar between partial responders to entecavir and non-responders to lamivudine.ConclusionsThe evolutionary patterns of HBV RT QS differ between responders and partial responders during the early stage of entecavir treatment. Characteristics of HBV QS evolution during the first 4 weeks contribute to the prediction of long-term virological responses. The similar patterns of HBV RT QS in partial responders and non-responders receiving different nucleoside analogues may imply a novel mechanism of drug resistance, which warrants further investigation.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>21292683</pmid><doi>10.1136/gut.2010.226225</doi><tpages>9</tpages></addata></record>
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source PubMed Central Free; MEDLINE; BMJ Journals - NESLi2
subjects Adolescent
Adult
Aged
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiretroviral drugs
Antiviral agents
Antiviral Agents - therapeutic use
antiviral therapy
Biological and medical sciences
chronic/drug therapy/virology
Clinical medicine
Deoxyribonucleic acid
DNA
DNA, Viral - blood
DNA, Viral - genetics
Drug dosages
Drug resistance
Drug Resistance, Viral - genetics
evolution
Evolution, Molecular
Female
Gastroenterology. Liver. Pancreas. Abdomen
genetic heterogeneity
Genetic Variation
genetics
Guanine - analogs & derivatives
Guanine - therapeutic use
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatitis B virus - classification
Hepatitis B virus - drug effects
Hepatitis B virus - genetics
Hepatitis B virus - isolation & purification
hepatitis B virus/drug effects/genetics
Hepatitis B, Chronic - drug therapy
Hepatitis B, Chronic - virology
Humans
Lamivudine - therapeutic use
Liver cirrhosis
Liver diseases
Male
Medical sciences
Middle Aged
molecular
Mutation
Pharmacology. Drug treatments
Phylogeny
Retrospective Studies
RNA-Directed DNA Polymerase - genetics
Selection, Genetic
Sequence Analysis, DNA - methods
Studies
Treatment Outcome
Young Adult
title Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy
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