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Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy

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Issue Date
2006-05-27
Publisher
Wiley-Blackwell
Citation
Hepatology. 2006 Jun;43(6):1385-91.
Keywords
Adenine/administration & dosage/*analogs & derivativesAdultAgedAntiviral Agents/*administration & dosageBase SequenceCase-Control StudiesDNA, Viral/analysisDose-Response Relationship, DrugDrug Administration ScheduleDrug Resistance, Multiple/*geneticsFemaleHepatitis B, Chronic/*drug therapy/geneticsHumansLamivudine/*administration & dosageMaleMiddle AgedMolecular Sequence DataMutationPharmacogeneticsPhosphonic Acids/*administration & dosageProbabilityReverse Transcriptase Polymerase Chain ReactionRisk AssessmentSeverity of Illness IndexStatistics, NonparametricTreatment OutcomeViral Load
Abstract
Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naive chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resistant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naive patients at 48 weeks of ADV monotherapy. Fifty-seven LAM-resistant patients and 38 treatment-naive patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real-time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, whereas none of the 38 treatment-naive patients developed such mutations (P < .01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs. -2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-naive patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.
ISSN
0270-9139 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16729316

http://dx.dor.org/10.1002/hep.21189

https://hdl.handle.net/10371/47063
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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