Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi

Translated title of the contribution: Investigation of baseline antiviral resistance in treatment-naive chronic hepatitis B cases

Koray Ergünay, Evrim Kahramanoǧlu Aksoy, Halis Şimşek, Alpaslan Alp, Burçin Şener, Gonca Tatar, Dürdal Us, Gülşen Hasçelik

Research output: Contribution to journalArticle

Abstract

Naturally-occuring mutations associated with resistance to nucleoside/nucleotide analogues (NA) can be detected in a group of treatment-naive individuals chronically infected with hepatitis B virus (HBV). Genotypic resistance testing prior to the initiation of NA therapy may facilitate the selection of optimal drug regime and help to prevent early emergence of clincal resistance. In this study, presence of resistance mutations in treatment-naive individuals with chronic hepatitis B (CHB) was investigated in Hacettepe University Hospital, a referral center in Ankara province, Turkey. A total of 42 patients (17 female, 25 male; age range: 18-62 years) diagnosed as CHB were enrolled in the study with informed consent. All of the patients were negative for hepatitis C and D viruses and human immunodeficiency virus coinfections, and none had a history of interferon or NA treatment. HBV viral load, HBV markers and hepatic enzymes in patients were determined via standardized commercial assays. For the detection of NA resistance mutations, a partial sequence of approximately 250 nucleotides, harboring the frequently-observed sites for NA resistance was amplified via nested PCR and characterized by direct sequencing of the amplicons. The sequences were handled and interpreted for the presence of mutations via various softwares and a web-based virtual phenotyping tool. Well-characterized sequences were obtained in 30 out of 42 samples (71.4%). All circulating HBV strains were observed as genotype D. Nucleotide variations were detected in 19 individuals (63.5%) that comprise silent mutations without amino acid substitution in 8 (26.6%), mutations with undetermined significance in 7 (23.3%) and mutations associated with NA resistance in 3 (10%) patients. Mutations conferring resistance to entecavir + lamivudine (S202C, M204V, L180M, T184N) were identified in one patient whereas L180P, A181Q and A194V substitutions associated with probable lamivudin + adefovir and tenofovir resistance, respectively, were detected in other patients. All patients with resistance mutations were HBsAg and HBeAg positive, anti-HBe negative and had viral loads exceeding 3 × 10 7 IU/ml. In two patients, the route for HBV transmission was vertical. Since no follow-up samples were available from individuals with resistance mutations, alterations in serological markers, viral load and mutation patterns could not be monitored. In conclusion, the presence of NA resistance mutations were revealed in treatment-naive CHB cases in a referral hospital in Turkey. The impact and cost-effectivity of detecting naturally-occuring resistance mutations for clinical follow-up prior to the antiviral therapy need to be elucidated by prospective studies.

Original languageTurkish
Pages (from-to)628-635
Number of pages8
JournalMikrobiyoloji Bulteni
Volume47
Issue number4
StatePublished - Oct 2013
Externally publishedYes

Fingerprint

Chronic Hepatitis B
Antiviral Agents
Mutation
Nucleotides
Hepatitis B virus
Therapeutics
Viral Load
Tenofovir
Turkey
Referral and Consultation
Hepatitis Delta Virus
Lamivudine
Hepatitis B e Antigens
Amino Acid Substitution
Hepatitis B Surface Antigens
Informed Consent
Coinfection
Nucleosides
Hepacivirus
Interferons

Keywords

  • Chronic
  • Hepatitis B
  • Hepatitis B virus
  • Mutation
  • Naive
  • Resistance
  • Treatment

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)
  • Immunology and Microbiology(all)

Cite this

Ergünay, K., Kahramanoǧlu Aksoy, E., Şimşek, H., Alp, A., Şener, B., Tatar, G., ... Hasçelik, G. (2013). Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi. Mikrobiyoloji Bulteni, 47(4), 628-635.

Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi. / Ergünay, Koray; Kahramanoǧlu Aksoy, Evrim; Şimşek, Halis; Alp, Alpaslan; Şener, Burçin; Tatar, Gonca; Us, Dürdal; Hasçelik, Gülşen.

In: Mikrobiyoloji Bulteni, Vol. 47, No. 4, 10.2013, p. 628-635.

Research output: Contribution to journalArticle

Ergünay, K, Kahramanoǧlu Aksoy, E, Şimşek, H, Alp, A, Şener, B, Tatar, G, Us, D & Hasçelik, G 2013, 'Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi', Mikrobiyoloji Bulteni, vol. 47, no. 4, pp. 628-635.
Ergünay K, Kahramanoǧlu Aksoy E, Şimşek H, Alp A, Şener B, Tatar G et al. Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi. Mikrobiyoloji Bulteni. 2013 Oct;47(4):628-635.
Ergünay, Koray ; Kahramanoǧlu Aksoy, Evrim ; Şimşek, Halis ; Alp, Alpaslan ; Şener, Burçin ; Tatar, Gonca ; Us, Dürdal ; Hasçelik, Gülşen. / Tedavi naif kronik hepatit B olgulannda bazal antiviral direncin araştirilmasi. In: Mikrobiyoloji Bulteni. 2013 ; Vol. 47, No. 4. pp. 628-635.
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