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  • SAGE Publications  (2)
  • Ahn, Sang Hoon  (2)
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  • SAGE Publications  (2)
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  • 1
    Online Resource
    Online Resource
    A 96-Week Randomized Trial of Switching to Entecavir in Chronic Hepatitis B Patients with a Partial Virological Response to Lamivudine
    SAGE Publications ; 2012
    In:  Antiviral Therapy Vol. 17, No. 8 ( 2012-11), p. 1563-1570
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 17, No. 8 ( 2012-11), p. 1563-1570
    Abstract: Growing numbers of chronic hepatitis B (CHB) patients in the Asia-Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96-week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virological response to lamivudine. Methods A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA≥60 IU/ml after ≥6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. Results Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log 10 IU/ml, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P 〈 0.001). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by week 4, maintained through week 96. Entecavir-switch patients with baseline HBV DNA 〈 5 log 10 IU/ml were more likely to achieve a virological response at week 96. A total of 6 (17.6%) entecavir-switch and 2 (5.7%) lamivudine- maintained patients achieved HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks. Conclusions Switching to entecavir in patients with a partial virological response to lamivudine resulted in increased virological efficacy and lower rates of antiviral resistance than maintaining lamivudine.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP2277
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Comparison of Multiplex Restriction Fragment Mass Polymorphism and Sequencing Analyses for Detecting Entecavir Resistance in Chronic Hepatitis B
    SAGE Publications ; 2011
    In:  Antiviral Therapy Vol. 16, No. 1 ( 2011-01), p. 77-87
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 16, No. 1 ( 2011-01), p. 77-87
    Abstract: Drug resistance is a major limitation to the long-term efficacy of controlling chronic hepatitis B (CHB). There is a growing need to analyse multiple mutations associated with drug resistance because sequential or combinational use of antivirals is increasingly being used in treatment. In this study, we introduced a multiplex restriction fragment mass polymorphism (RFMP) assay for detecting mutations conferring entecavir and lamivudine resistance, and compared its performance with direct or clonal sequencing assays. Methods Multiplex PCR was performed with mixed primers designed to interrogate rt184, rt202, rt204 and rt250. The PCR products were digested with restriction enzymes and the resulting fragments were analysed by mass spectrometry. A total of 251 serum samples, taken serially from 45 patients who received entecavir treatment after confirmed diagnosis of lamivudine resistance and inadequate adefovir dipivoxil response, were analysed by the multiplex RFMP assay. Results The multiplex RFMP assay correctly identified known viral sequences with sufficient analytical sensitivity to detect as few as 100 IU/ml of HBV and with superior ability to determine haplotypes composed of neighbouring variations. Complex mutational patterns and relative abundances determined by multiplex RFMP assay were in good concordance with results obtained by direct or clonal sequencing analyses. Defined mixtures were successfully and consistently identified at 2% relative concentration of mutant versus wild-type virus by the assay. Conclusions The multiplex RFMP assay is an accurate and sensitive means to detect entecavir and lamivudine resistance mutations, simultaneously. The method is expected to enable early and efficient diagnosis of multiple drug resistance mutations for optimal management of CHB.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.3851/IMP1702
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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