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Conference Paper: Effects Of Hepatitis B Virus Quasispecies And Reverse Transcriptase Variants On Treatment Responsiveness To Entecavir

TitleEffects Of Hepatitis B Virus Quasispecies And Reverse Transcriptase Variants On Treatment Responsiveness To Entecavir
Authors
Issue Date2013
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
The 48th Annual Meeting of the European Association for the Study of the Liver, Amsterdam, The Netherlands, 24-28 April 2013. In Journal of Hepatology, 2013, v. 58 n. Suppl. 1, p. S317, abstract no. 779 How to Cite?
AbstractBackground and Aims: Entecavir therapy reduces hepatitis B virus (HBV) DNA to an undetectable level in around 60–80% of patients after 1 year of treatment, but HBV DNA may remain detectable in the remaining patients. We aimed to determine whether baseline HBV reverse transcriptase (rt) sequence polymorphisms and quasispecies complexity and diversity are associated with the differences in treatment response. Methods: Pre-treatment HBV rt sequence from 305 entecavir-treated patients were determined by DNA sequencing. Sequencing data were associated with their virological outcome, as defined by optimal response (undetectable HBV DNA at year 1) or partial response (HBV DNA >60 copies/mL). Quasispecies complexity and diversity were determined using MEGA 5.0 software. Results: Seventeen rt variants were more frequently detected in the partial responders (n = 64; 21%) than in the optimal responders (all P <0.05). Multivariate analysis revealed that high baseline HBV DNA, hepatitis B e antigen (HBeAg)-positivity and rt124N were associated with partial entecavir response. Compared with the partial responders, the optimal responders had a higher quasispecies complexity at nucleotide and amino acid levels (P = 0.036 and 0.087, respectively) and higher quasispecies diversity, as reflected by a greater genetic distance at both nucleotide and amino acid levels (P = 0.019 and 0.032, respectively) and a greater number of synonymous substitutions per synonymous site (dS; P = 0.015) and number of non-synonymous substitutions per non-synonymous site (dN; P = 0.039). Conclusions: High baseline HBV DNA, HBeAg-positivity and rt124N were associated with partial entecavir response at year 1. Baseline HBV quasispecies complexity and diversity were higher in the optimal responders than in the partial responders.
DescriptionFulltext in: http://www2.kenes.com/liver-congress/scientific/Documents/Abstract_book.pdf
Poster Session: 07c. Viral Hepatitis B & D: Clinical (Therapy, New Compounds, Resistance)
Persistent Identifierhttp://hdl.handle.net/10722/185005
ISSN
2015 Impact Factor: 10.59
2015 SCImago Journal Rankings: 4.570

 

DC FieldValueLanguage
dc.contributor.authorWong, DKHen_US
dc.contributor.authorKopaniszen, Men_US
dc.contributor.authorFung, JYYen_US
dc.contributor.authorSeto, WKWen_US
dc.contributor.authorHuang, FYen_US
dc.contributor.authorLai, CLen_US
dc.contributor.authorYuen, RMFen_US
dc.date.accessioned2013-07-15T10:23:47Z-
dc.date.available2013-07-15T10:23:47Z-
dc.date.issued2013en_US
dc.identifier.citationThe 48th Annual Meeting of the European Association for the Study of the Liver, Amsterdam, The Netherlands, 24-28 April 2013. In Journal of Hepatology, 2013, v. 58 n. Suppl. 1, p. S317, abstract no. 779en_US
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/185005-
dc.descriptionFulltext in: http://www2.kenes.com/liver-congress/scientific/Documents/Abstract_book.pdf-
dc.descriptionPoster Session: 07c. Viral Hepatitis B & D: Clinical (Therapy, New Compounds, Resistance)-
dc.description.abstractBackground and Aims: Entecavir therapy reduces hepatitis B virus (HBV) DNA to an undetectable level in around 60–80% of patients after 1 year of treatment, but HBV DNA may remain detectable in the remaining patients. We aimed to determine whether baseline HBV reverse transcriptase (rt) sequence polymorphisms and quasispecies complexity and diversity are associated with the differences in treatment response. Methods: Pre-treatment HBV rt sequence from 305 entecavir-treated patients were determined by DNA sequencing. Sequencing data were associated with their virological outcome, as defined by optimal response (undetectable HBV DNA at year 1) or partial response (HBV DNA >60 copies/mL). Quasispecies complexity and diversity were determined using MEGA 5.0 software. Results: Seventeen rt variants were more frequently detected in the partial responders (n = 64; 21%) than in the optimal responders (all P <0.05). Multivariate analysis revealed that high baseline HBV DNA, hepatitis B e antigen (HBeAg)-positivity and rt124N were associated with partial entecavir response. Compared with the partial responders, the optimal responders had a higher quasispecies complexity at nucleotide and amino acid levels (P = 0.036 and 0.087, respectively) and higher quasispecies diversity, as reflected by a greater genetic distance at both nucleotide and amino acid levels (P = 0.019 and 0.032, respectively) and a greater number of synonymous substitutions per synonymous site (dS; P = 0.015) and number of non-synonymous substitutions per non-synonymous site (dN; P = 0.039). Conclusions: High baseline HBV DNA, HBeAg-positivity and rt124N were associated with partial entecavir response at year 1. Baseline HBV quasispecies complexity and diversity were higher in the optimal responders than in the partial responders.-
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatologyen_US
dc.titleEffects Of Hepatitis B Virus Quasispecies And Reverse Transcriptase Variants On Treatment Responsiveness To Entecaviren_US
dc.typeConference_Paperen_US
dc.identifier.emailWong, DKH: danywong@hku.hken_US
dc.identifier.emailKopaniszen, M: malkop@hku.hken_US
dc.identifier.emailFung, JYY: jfung@hkucc.hku.hken_US
dc.identifier.emailSeto, WKW: wkseto2@hku.hken_US
dc.identifier.emailHuang, FY: camy@graduate.hku.hken_US
dc.identifier.emailLai, CL: hrmelcl@hku.hken_US
dc.identifier.emailYuen, RMF: mfyuen@hku.hken_US
dc.identifier.authorityWong, DKH=rp00492en_US
dc.identifier.authorityFung, JYY=rp00518en_US
dc.identifier.authoritySeto, WKW=rp01659en_US
dc.identifier.authorityLai, CL=rp00314en_US
dc.identifier.doi10.1016/S0168-8278(13)60781-3-
dc.identifier.hkuros215588en_US
dc.identifier.volume58en_US
dc.identifier.issueSuppl. 1-
dc.identifier.spageS317, abstract no. 779en_US
dc.identifier.epageS317, abstract no. 779en_US
dc.publisher.placeNetherlands-

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