ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism for adefovir dipivoxil (ADV) resistance occurred in chronic hepatitis B patients of a series of phase III clinical trails.</p><p><b>METHODS</b>30 resistant HBV strains were selected out from 177 cases of ADV treated chronic hepatitis B patients. HBV polymerase RT region were amplified by nested PCR and analyzed with the standard nucleotide sequence of HBV strains deposited in GeneBank.</p><p><b>RESULTS</b>21 out of 30 HBV strains were primary resistant strains, among them 5 HBV strains (23.8%, 5/21) had the polymorphism site of rtN118H. While the other 9 HBV strains showed secondary resistance, variations in conservative region C (rtM207V) and other non-conservative regions were found. The classic mutation sites such as rtN236T and rtA181V/T were not found.</p><p><b>CONCLUSIONS</b>Polymorphism site of rtN118H might be responsible for HBV primary resistance to ADV therapy. rtM207V variation in HBV RT C domain and other variation sites might play a role in HBV secondary resistance to ADV treatment, and natural resistant quasispecies may be the basis for the ADV quick resistance. These conclusions await further confirmation by phenotype test.</p>
Subject(s)
Adult , Female , Humans , Male , Adenine , Pharmacology , Therapeutic Uses , Alanine Transaminase , Blood , Amino Acid Sequence , Antiviral Agents , Pharmacology , Therapeutic Uses , Base Sequence , DNA Primers , DNA, Viral , Blood , Drug Resistance, Viral , Genotype , Hepatitis B virus , Genetics , Hepatitis B, Chronic , Drug Therapy , Genetics , Virology , Molecular Sequence Data , Organophosphonates , Pharmacology , Therapeutic Uses , Polymorphism, Genetic , Genetics , RNA-Directed DNA Polymerase , Genetics , Reverse Transcriptase Inhibitors , Pharmacology , Therapeutic Uses , Reverse Transcriptase Polymerase Chain Reaction , Methods , Sequence Analysis, DNAABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of HBV genotypes on their response to adefovir dipivoxil (ADV) antiviral therapy.</p><p><b>METHODS</b>HBV genotypes from 177 HBeAg-positive chronic hepatitis B (CHB) patients were identified and the patients were treated with ADV 10 mg per day for 48 weeks. The clinical data in terms of serum HBV DNA seroclearance, mean HBV DNA reduction (log value), HBeAg loss, anti-HBe seroconversion and serum ALT of those patients were analyzed against their HBV genotypes.</p><p><b>RESULTS</b>Genotype B and genotype C were found in 102 and 65 cases, respectively. The mean HBV DNA reduction in patients with genotype B and genotype C at their treatment times of 12, 24 and 48 weeks was 2.2 log10copies/ml, 2.1 log10copies/ml (P more than 0.05), 2.7 log10copies/ml, 2.4 log10copies/ml (P more than 0.05) and 3.6 log10copies/ml, 3.1 log10copies/ml (P less than 0.05), respectively. At the end of the therapy (48 weeks), 43 (42.2%) patients with genotype B HBV infection and 22 (33.8%) patients with genotype C HBV infection had achieved HBV DNA seroclearance (P less than 0.05).</p><p><b>CONCLUSIONS</b>Our results suggest that genotype B HBV has a better virological response to ADV therapy in HBeAg-positive chronic hepatitis B patients than that of genotype C. Longer terms of ADV treatment are needed to confirm this conclusion.</p>