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College of Medicine/School of Medicine (의과대학/대학원)
Molecular and Genomic Medicine (분자유전체의학전공)
Journal Papers (저널논문_분자유전체의학전공)
Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy
- Authors
- Issue Date
- 2006-05-27
- Publisher
- Wiley-Blackwell
- Citation
- Hepatology. 2006 Jun;43(6):1385-91.
- Keywords
- Adenine/administration & dosage/*analogs & derivatives ; Adult ; Aged ; Antiviral Agents/*administration & dosage ; Base Sequence ; Case-Control Studies ; DNA, Viral/analysis ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Resistance, Multiple/*genetics ; Female ; Hepatitis B, Chronic/*drug therapy/genetics ; Humans ; Lamivudine/*administration & dosage ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pharmacogenetics ; Phosphonic Acids/*administration & dosage ; Probability ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Assessment ; Severity of Illness Index ; Statistics, Nonparametric ; Treatment Outcome ; Viral 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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