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.
Intervirology
; 53(4): 203-10, 2010.
Article
en En
| MEDLINE
| ID: mdl-20332649
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adenina
/
Virus de la Hepatitis B
/
Regiones Promotoras Genéticas
/
ADN Polimerasa Dirigida por ARN
/
Hepatitis B Crónica
/
Organofosfonatos
/
Antígenos del Núcleo de la Hepatitis B
/
Mutación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Intervirology
Año:
2010
Tipo del documento:
Article