title: Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients.
abstract: Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.
authors.affiliation: Department of Virology and Fundamental Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Sevim
authors.initials: S
authors.lastname: Mese
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Arikan
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Aris
authors.initials: A
authors.lastname: Cakiris
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Abaci
authors.affiliation: Department of Computer Engineering, Istanbul University, Istanbul, Turkey.
authors.forename: Ergun
authors.initials: E
authors.lastname: Gumus
authors.affiliation: Department of Computer Engineering, Istanbul University, Istanbul, Turkey.
authors.forename: Olcay
authors.initials: O
authors.lastname: Kursun
authors.affiliation: Department of Virology and Fundamental Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Onel
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Duran
authors.initials: D
authors.lastname: Ustek
authors.affiliation: Department of Gastroenterology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Kaymakoglu
authors.affiliation: Department of Virology and Fundamental Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Badur
authors.affiliation: Department of Virology and Fundamental Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Osman Sadi
authors.initials: OS
authors.lastname: Yenen
authors.affiliation: Department of Virology and Fundamental Immunology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Bozkaya
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D009711:Nucleotides; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase