title: An initial assessment of correlations between host- and virus-related factors affecting analogues antiviral therapy in HBV chronically infected patients.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Stalke
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Magda
authors.initials: M
authors.lastname: Rybicka
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wróblewska
authors.affiliation: Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Dreczewski
authors.affiliation: Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Stracewska
authors.affiliation: Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Smiatacz
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Krzysztof Piotr
authors.initials: KP
authors.lastname: Bielawski
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D058605:Host-Derived Cellular Factors / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D019259:Lamivudine / Q000494:pharmacology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009705:Nucleosides / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics; D012737:Sex Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D058605:Host-Derived Cellular Factors; D009705:Nucleosides; D063065:Organophosphonates; D016753:Interleukin-10; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine