Aims: The long-term efficacy of adefovir dipivoxil in combination with lamivudine to chronic hepatitis B virus (HBV) infection is still unclear. Methods: Virological response and hepatocarcinogenesis during lamivudine + adefovir were investigated in 183 lamivudine-resistant Japanese patients with chronic genotype C-dominant HBV infection. As the predictors of virological response, an assessment of clinical parameters and a nucleotide (nt) sequence analysis of the negative regulatory element to core gene (nt 1611–2450) were performed at the start of adefovir. Results: The cumulative HBV-DNA non-detectable and ALT normalization rates were 93.6 and 97.6% at the end of 3 years, respectively. Multivariate analysis identified total bilirubin, AST, and nt substitutions (nt 1762, 1768, 1846, 1896, 2134, 2288, 2441) as determinants of early non-detectable HBV-DNA. The yearly incidence of hepatocellular carcinoma (HCC) during the first 3 years was 2.7%. At the diagnosis of HCC, ALT normalization, HBV-DNA non-detectable, and HBeAg-seronegative conversion rates were 75.0, 83.3, and 57.1%, respectively. Furthermore, the cumulative HBV-DNA non-detectable and ALT normalization rates were not significantly different according to the development of HCC or not. Conclusions: Lamivudine-resistant patients treated with lamivudine + adefovir could achieve the excellent virological response and biochemical response, but the low hepatitis activity was not enough to suppress hepatocarcinogenesis.

Keywords:
Hepatitis B virus, Lamivudine, Adefovir dipivoxil, Hepatocellular carcinoma, Basic core promoter, Precore, Core region
This content is only available via PDF.
© 2009 S. Karger AG, Basel
2009
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.