26 February 2014 : Research paper
An initial assessment of correlations between host- and virus-related factors affecting analogues antiviral therapy in HBV chronically infected patientsPiotr StalkeABCDE, Magda RybickaBCDEF, Anna WroblewskaC, Marcin DreczewskiB, Ewa StracewskaB, Tomasz SmiataczG, Krzysztof Piotr BielawskiACDEFG
Med Sci Monit 2014; 20:321-328
BACKGROUND: Success in treating hepatitis B virus (HBV) infection with nucleoside analogues drugs is limited by the emergence of drug-resistant viral strains upon prolonged therapy. In addition to mutation patterns in the viral polymerase gene, host factors are assumed to contribute to failure of treatment in chronic HBV infections. The aim of this study was to analyze the correlation between efficacy of antiviral therapy and the prevalence of HBV pretreatment drug-resistant variants. We also analyzed the role of heterogeneity in the promoter region of the IL-10 on the HBV pol/s gene polymorphisms and efficacy of analogues-driven therapy.
MATERIAL AND METHODS: HBV DNA was extracted from 54 serum samples from chronic hepatitis B (CHB) patients. Drug-resistance mutations were analyzed using MALDI-TOF mass spectrometry technology (MALDI-TOF MS) and Multi-temperature single-strand conformation polymorphism (MSSCP). IL-10 gene promoter region polymorphisms at positions -1082, -819, and -592 were determined in allele-specific PCR reactions (AS-PCR).
RESULTS: Drug-resistance mutations were detected in 74% of naïve and 93% of experienced patients, but the effect of pre-existence of drug-resistant HBV variants on antiviral therapy was not statistically significant (p=0.86). The role of polymorphisms at positions –1082 (p=0.88), –819 (p=0.26), and –592 (p=0.26) of IL-10 promoter region polymorphisms was excluded from the response-predicting factors. The main host factors predicting successful response to antiviral therapy were female sex (p=0.007) and young age (p=0.013).
CONCLUSIONS: The presence of drug-resistant HBV variants in baseline is not a viral predictor of good response to nucleoside/nucleotide analogues therapy. Only low HBV viral load predicted positive response to antiviral therapy. The ideal candidate for antiviral therapy is an immunocompetent, young female with low HBV viral load and elevated ALT activity.
Keywords: Adenine - pharmacology, Hepatitis B, Chronic, Antiviral Agents - pharmacology, Drug Resistance, Viral - genetics, Drug Therapy, Combination, Hepatitis B, Chronic - virology, Host-Derived Cellular Factors - genetics, Interleukin-10 - genetics, Lamivudine - pharmacology, Mutation - genetics, Nucleosides - pharmacology, Organophosphonates - pharmacology, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Promoter Regions, Genetic - genetics, Sex Factors, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Viral Load
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