Objective: The aim of this study was to predict breakthrough hepatitis and analyze the dynamics of lamivudine-resistant hepatitis B virus in patients treated with lamivudine. Methods: Fifty-five chronic hepatitis B patients treated with lamivudine were included. The emergence of YMDD motif mutants was detected by peptide nucleic acid (PNA) mediated PCR clamping with a detection limit of 101 YMDD mutants. We then performed a semiquantitative PCR assay of subjects in whom YMDD mutants were detected. This assay detects 102.7–107.7 copies of mutant virus per 1 ml of serum. Results: YMDD mutants were detected in 28 (51%) of the 55 patients. Eight patients stopped medication before viral breakthrough. YMDD mutants appeared transiently despite the continuance of lamivudine therapy in 12 patients. In all 8 patients with breakthrough hepatitis, the quantities of YMDD mutants ranged from 102.7–104.7 copies/ml in the two to three months before clinical breakthrough. In contrast, in 12 patients without viral breakthrough, there were always less than 102.7 copies/ml YMDD mutants. Conclusions: Lamivudine-resistant viruses sometimes disappear even during lamivudine administration. Our sensitive quantitative assay proved useful for early detection of YMDD mutants and a threshold of 102.7 copies/ml is suggested for predicting viral breakthrough.

Keywords:
Hepatitis B virus, Lamivudine resistance, Breakthrough hepatitis, Peptide nucleic acids, PCR clamping
This content is only available via PDF.
© 2006 S. Karger AG, Basel
2006
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.