Low risk of adefovir resistance in lamivudine-resistant chronic hepatitis B patients treated with adefovir plus lamivudine combination therapy: two-year follow-up.

Abstract

BACKGROUND/AIMS:

We studied the long-term efficacy (median follow-up of 28 months) of adefovir (ADV) in combination with lamivudine (LAM) in 132 LAM-resistant Japanese patients with chronic genotype C-dominant hepatitis B virus (HBV) infection.

METHODS:

The viral response (undetectable HBV-DNA by PCR assay) and the predictor of viral response were evaluated. The emergence of ADV-resistant mutants was investigated during the combination therapy.

RESULTS:

The cumulative probability of viral response was 69% at 12 months, and 81% at 24 months. Multivariate analysis identified baseline HBe antigen status (P=0.0001), aspartate aminotransferase level (AST) (P=0.001) and HBV-DNA level (P=0.002) as determinants of viral response to treatment. At the beginning of ADV therapy, substitutions at rtA181 (rtA181T and rtA181S) were identified in 3 patients (2.3%). In the remaining 129 patients, the rtM204 mutants were identified at baseline, and two (1.6%) of the 129 patients developed new ADV-resistant mutants; one was rtA181S and another was rtA181T plus rtN236T mutation.

CONCLUSIONS:

Adefovir and lamivudine combination therapy effectively suppressed viral replication and maintained the efficacy well in LAM-resistant patients with chronic HBV infection. Genotypic analysis indicated that the emergence of ADV-resistant mutants is rare, at least over a period of 2 years, in patients with combination therapy.

• Authors: Hiromi Yatsuji, Fumitaka Suzuki, Hitomi Sezaki, Norio Akuta, Yoshiyuki Suzuki, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Sachiyo Watahiki, Satomi Iwasaki, Mariko Kobayashi, Hiromitsu Kumada
• Journal: Journal of hepatology (J Hepatol) Vol. 48 Issue 6 Pg. 923-31 (Jun 2008) ISSN: 0168-8278 [Print] Netherlands
• PMID: 18433925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• DNA, Viral
• Organophosphonates
• Lamivudine
• adefovir
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology, therapeutic use)
• Adult
• Aged
• Antiviral Agents (pharmacology, therapeutic use)
• DNA, Viral (blood)
• Dose-Response Relationship, Drug
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Genotype
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (drug therapy, genetics)
• Humans
• Lamivudine (pharmacology, therapeutic use)
• Male
• Middle Aged
• Multivariate Analysis
• Mutation (genetics)
• Organophosphonates (pharmacology, therapeutic use)
• Risk Factors
• Treatment Outcome
• Virus Replication (drug effects)