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Original Paper

Response to Adefovir Depends on Mutation Patterns in Precore Region, Basal Core Promoter and Reverse Transcriptase, and On-Treatment Responses in Lamivudine-Resistant Chronic Hepatitis B Patients

Song B.-C.a · Cui X.J.a · Shin J.W.b · Park N.H.b · Cho Y.-K.a · Song H.J.a · Hyun S.a · Jeong S.U.a · Choi E.K.a · Kim H.U.a

Author affiliations

aDepartment of Internal Medicine, Jeju National University School of Medicine, Jeju, and bDepartment of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea

Corresponding Author

Byung-Cheol Song, MD

Department of Internal Medicine

Jeju National University School of Medicine

1753-3 Ara-dong, Jeju 690-716 (Republic of Korea)

Tel. +82 64 717 1528, Fax +82 64 717 1131, E-Mail drsong@jejunu.ac.kr

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Intervirology 2010;53:203–210

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Abstract

Objective: In vitro studies showed that mutations in the basal core promoter (BCP) or precore (PC) region restore the replication inefficiency of the lamivudine-resistant mutant. The aim of this study was to clarify the effect of molecular characteristics on the antiviral response to adefovir in patients with lamivudine-resistant chronic hepatitis B (CHB). Methods: Sixty-six lamivudine-resistant patients who were treated with adefovir monotherapy were studied. Sequences of BCP, PC region and reverse transcriptase were determined before adefovir therapy. In patients with virologic breakthrough, reverse transcriptase sequencing was performed. Results: The cumulative probabilities of virologic response were 23.3, 46, 52.7 and 59.5% at years 1, 2, 3 and 4, respectively. PC mutation, the absence of compensatory mutations (rtL80I/V or rtV173L), and a decrease in serum hepatitis B virus (HBV) DNA by 3 log or greater at 6 months were independent predictors of virologic response. The cumulative probabilities of virologic breakthrough were 0, 12.9, 30.7 and 44.5% at years 1, 2, 3 and 4, respectively. BCP mutation and a less than 3 log decrease in serum HBV DNA at 6 months were 2 independent risk factors for virologic breakthrough. Conclusion: Response to adefovir depends on mutation patterns in the BCP, PC region and reverse transcriptase, and on-treatment decreases in serum HBV DNA in lamivudine-resistant CHB patients.

© 2010 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: October 06, 2009
Accepted: December 22, 2009
Published online: March 23, 2010
Issue release date: June 2010

Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 3

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

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