35 352

Cited 0 times in

Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B.

Authors
Cha, CK; Kwon, HC; Cheong, JY; Cho, SW; Hong, SP; Kim, SO; Yoo, WD
Citation
Journal of medical virology, 81(3):417-424, 2009
Journal Title
Journal of medical virology
ISSN
0146-66151096-9071
Abstract
Adefovir has a potent antiviral activity as a rescue treatment against lamivudine-resistant strains. The aim of this study was to assess the patterns of lamivudine-resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty-seven patients with lamivudine-resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine-resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real-time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%) rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M, rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was always observed in conjunction with rtM204I. Decrease in mean serum HBV did not differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (-3.3 vs. -3.3 log(10) copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL80I mutant is co-selected with rtM204I as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine-resistant HBV mutations.
MeSH terms
Adenine/analogs & derivatives*Adenine/pharmacologyAdenine/therapeutic useAdultAntiviral Agents/pharmacologyAntiviral Agents/therapeutic use*DNA Mutational AnalysisDNA, Viral/geneticsDrug Resistance, Viral*FemaleHepatitis B virus/drug effects*Hepatitis B virus/geneticsHepatitis B, Chronic/virology*HumansLamivudine/pharmacologyLamivudine/therapeutic use*MaleMiddle AgedMutation, MissensePhosphonic Acids/pharmacologyPhosphonic Acids/therapeutic use*Polymorphism, Restriction Fragment LengthSequence Analysis, DNASerum/virologyViral Load
DOI
10.1002/jmv.21402
PMID
19152409
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
AJOU Authors
정, 재연조, 성원
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse