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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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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fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_904482229</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>904482229</sourcerecordid><originalsourceid>FETCH-LOGICAL-b459t-b4fc555d50c3942aa76317062c8941177ac0d5830de4895f50f2cc0c19b608c53</originalsourceid><addsrcrecordid>eNqFkctv1DAQxiMEotvCmRuyhBASUlo_E7s32LaAVMGFl7hYXmdMvWST1I-F3vjTcbRLkbj0MqORf_PpG39V9YTgY0JYc_I9p2OKy0RpQ6m4Vy0Ib2TNqJT3qwXGpK1Fy9VBdRjjGmMspSIPqwNKqKKNZIvq9_l27HPy42DCDZpMShCGiEaHrqBMPvmIXqOtDzmi62yijxNYDxHloYOAOu8cBBgSitCDTX4LaAoQYy7lFNkxBOjNLI9--nSFzFAQH0yPwDlvjb15VD1wpo_weN-Pqk8X5x-Xb-vLD2_eLV9d1isuVCrVWSFEJ7BlilNj2oaRFjfUSsUJaVtjcSckwx1wqYQT2FFrsSVq1WBpBTuqXux0pzBeZ4hJb3y00PdmgDFHrTDnklKq7iSlYi1ljPJCPvuPXI85DOUMXRwpJjCTbaFOdpQNY4wBnJ6C35Tv1gTrOUVdUtRzinqXYtl4utfNqw10t_zf2ArwfA-YaE3vghmsj_84zme52WC943xM8Ov23YQfumlZK_T7z0tNv4gL_O3rmZ5Pf7njV5v1nS7_AJYswsk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779350387</pqid></control><display><type>article</type><title>Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy</title><source>PubMed Central Free</source><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><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</creator><creatorcontrib>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</creatorcontrib><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><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 & 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</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&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 & 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 & 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 & 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 & 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 & 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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & 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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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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T04%3A27%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evolutionary%20patterns%20of%20hepatitis%20B%20virus%20quasispecies%20under%20different%20selective%20pressures:%20correlation%20with%20antiviral%20efficacy&rft.jtitle=Gut&rft.au=Liu,%20Feng&rft.date=2011-09-01&rft.volume=60&rft.issue=9&rft.spage=1269&rft.epage=1277&rft.pages=1269-1277&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gut.2010.226225&rft_dat=%3Cproquest_cross%3E904482229%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779350387&rft_id=info:pmid/21292683&rfr_iscdi=true |