title: Analysis of potential antiviral resistance mutation profiles within the HBV reverse transcriptase in untreated chronic hepatitis B patients using an ultra-deep pyrosequencing method.
abstract: The potential antiviral resistance mutations within hepatitis B virus (HBV) reverse transcriptase (RT) region for nucleos(t)ide analogues (NA) are not well known. Especially, the effect of pre-existing antiviral drug resistance mutations in untreated patients in comparison to the resistance developed after treatment is not still clear. Sixteen naive chronic hepatitis B patients were studied. None of the patients had received NA treatment prior to the serum samples being collected. Forty-two potential NA resistance (NAr) mutation sites were screened by ultra-deep pyrosequencing (UDPS). After therapy, mutations conferring treatment resistance were detected by LiPA. Serum samples taken before treatment showed no classic primary or compensatory/secondary drug resistance mutations. However, NAr mutations found in 6 isolates (37.5%) involved 7 positions including rtL91I, rtT128I, rtQ215P, rtF221Y, rtN238D, rtC256S, and rtI266G. Substitutions at 3 NAr mutation sites (rtT128I, rtN238D, and rtC256S) were detected in 3 unresponsive patients developing drug resistance after NA treatment. One patient with rtI266G mutation also developed drug resistance after lamivudine (LAM) therapy. However, the relationship between rtI266G mutation and NA drug resistance was not previously reported. These results suggest that association of potential mutations besides the primary and secondary/compensatory resistance mutations should be investigated. Investigation of NAr mutations before treatment may be important for the success of the treatment.
authors.affiliation: Department of Microbiology, Faculty of Dentistry, Istanbul University, 34390 Istanbul, Turkey. Electronic address: sevgiciftci@gmail.com.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Ciftci
authors.affiliation: Department of Microbiology, Faculty of Dentistry, Istanbul University, 34390 Istanbul, Turkey.
authors.forename: Fahriye
authors.initials: F
authors.lastname: Keskin
authors.affiliation: Institute for Experimental Medical Research, Istanbul University, 34393 Istanbul, Turkey.
authors.forename: Aris
authors.initials: A
authors.lastname: Cakiris
authors.affiliation: Department of Gastroenterohepatology, Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Akyuz
authors.affiliation: Department of Gastroenterohepatology, Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey.
authors.forename: Binnur
authors.initials: B
authors.lastname: Pinarbasi
authors.affiliation: Institute for Experimental Medical Research, Istanbul University, 34393 Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Abaci
authors.affiliation: Institute for Experimental Medical Research, Istanbul University, 34393 Istanbul, Turkey.
authors.forename: Erdinc
authors.initials: E
authors.lastname: Dincer
authors.affiliation: Microbiology and Clinical Microbiology, Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Badur
authors.affiliation: Department of Gastroenterohepatology, Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Kaymakoglu
authors.affiliation: Institute for Experimental Medical Research, Istanbul University, 34393 Istanbul, Turkey.
authors.forename: Duran
authors.initials: D
authors.lastname: Ustek
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D058889:Molecular Typing / Q000379:methods; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult
chemical_list: D000998:Antiviral Agents
keywords: HBV-RT domain; Potential mutations; UDPS; Untreated chronic patients