Bir Yildan Uzun Süreli Antiviral ílaç Kullanan Kronik Hepatit B Hastalarinda Direnç Mutasyonlarinin Saptanmasi

Translated title of the contribution: Detection of resistance mutations in chronic hepatitis B patients receiving antiviral therapy for over one year

Sibel Aydoǧan, Koray Ergünay, Yasemin Balaban, Alpaslan Alp, Halis Şmşek, Gonca Tatar, Gülşen Hascelik, U. S. Dürdal

Research output: Contribution to journalArticle

Abstract

Primary mutations conferring hepatitis B virus (HBV) antiviral resistance and associated secondary/compensatory mutations were investigated in this study by DNA sequencing (SEQ) and two commercial Line Probe Assays (LiPAs) (Inno-Lipa HBV DRv2 and Inno-Lipa HBV DRv3, lnnogenetics, Belgium). A total of 71 subjects under follow-up for chronic hepatitis B and receiving lamivudine (LVD) therapy for one year or longer at the Hacettepe University Faculty of Medicine, Department of Internal Medicine, Gastroenterology Unit were included in the study with informed consent. Male to female ratio and mean age was noted as 47/24 and 43 ± 15.8 (age range: 13-71) years, respectively. Twenty samples with low HBV DNA levels (mean: 204.6 lU/ml) could not be interpreted by SEQ due to insufficient amplification. All samples with a positive consensus PCR were further analysed via LiPAs, as directed by the manufacturer. Thus a total of 51 and 56 samples could be evaluated via SEQ and LiPA assays, respectively. In 13 of the 51 (25.5%) samples by SEQ and in 9 of 56 (16%) samples by LiPAs, primary and compensatory mutations associated with resistance were identified. Multiple mutations that comprise LI 8OM + M204l in four and L18OM + M204V in one sample and single mutations (M204l) in three samples were identified by SEQ. In one sample which had multiple mutations associated with LVD resistance single mutations (S202G, N236T) associated with entecavir resistance and in two other such samples mutations associated with adefovir resistance were detected by SEQ. Also, in three samples aminoacid substitution at position rt215 (Q-S) as alone and in one sample with multiple mutations were observed via SEQ. In five of nine samples primary and compensatory multiple mutations (LI 80M + M204I in one sample, L80I + L18OM + M204I in two samples, L80I/V + M204I in one sample) and primary single mutations associated with LVD resistance (M204I/V) in four samples were detected by Inno-Lipa HBV DRv2. Two different mutations (G202, ILFM184) were observed in two samples with multiple mutations associated LVD resistance via Inno-Lipa HBV DRv3. However, mutation at position rt184 was evaluated as a weak positive. Any mutation associated with adefovir resistance was not detected by LiPA. As a result, SEQ and LiPAs displayed comparable performances for the detection of HBV drug resistance mutations. We suggested that for the evaluation of discordant results, it should be better to test consecutive serum samples.

Original languageTurkish
Pages (from-to)472-481
Number of pages10
JournalMikrobiyoloji Bulteni
Volume47
Issue number3
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

Chronic Hepatitis B
Antiviral Agents
Mutation
Hepatitis B virus
Lamivudine
Therapeutics
Belgium
Gastroenterology
Internal Medicine
Informed Consent
DNA Sequence Analysis
Drug Resistance

Keywords

  • Antiviral drug resistance
  • Dna sequencing
  • Hepatitis b virus
  • Line probe assays.

ASJC Scopus subject areas

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

Cite this

Aydoǧan, S., Ergünay, K., Balaban, Y., Alp, A., Şmşek, H., Tatar, G., ... Dürdal, U. S. (2013). Bir Yildan Uzun Süreli Antiviral ílaç Kullanan Kronik Hepatit B Hastalarinda Direnç Mutasyonlarinin Saptanmasi. Mikrobiyoloji Bulteni, 47(3), 472-481. https://doi.org/10.5578/mb.5625

Bir Yildan Uzun Süreli Antiviral ílaç Kullanan Kronik Hepatit B Hastalarinda Direnç Mutasyonlarinin Saptanmasi. / Aydoǧan, Sibel; Ergünay, Koray; Balaban, Yasemin; Alp, Alpaslan; Şmşek, Halis; Tatar, Gonca; Hascelik, Gülşen; Dürdal, U. S.

In: Mikrobiyoloji Bulteni, Vol. 47, No. 3, 07.2013, p. 472-481.

Research output: Contribution to journalArticle

Aydoǧan, S, Ergünay, K, Balaban, Y, Alp, A, Şmşek, H, Tatar, G, Hascelik, G & Dürdal, US 2013, 'Bir Yildan Uzun Süreli Antiviral ílaç Kullanan Kronik Hepatit B Hastalarinda Direnç Mutasyonlarinin Saptanmasi', Mikrobiyoloji Bulteni, vol. 47, no. 3, pp. 472-481. https://doi.org/10.5578/mb.5625
Aydoǧan, Sibel ; Ergünay, Koray ; Balaban, Yasemin ; Alp, Alpaslan ; Şmşek, Halis ; Tatar, Gonca ; Hascelik, Gülşen ; Dürdal, U. S. / Bir Yildan Uzun Süreli Antiviral ílaç Kullanan Kronik Hepatit B Hastalarinda Direnç Mutasyonlarinin Saptanmasi. In: Mikrobiyoloji Bulteni. 2013 ; Vol. 47, No. 3. pp. 472-481.
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abstract = "Primary mutations conferring hepatitis B virus (HBV) antiviral resistance and associated secondary/compensatory mutations were investigated in this study by DNA sequencing (SEQ) and two commercial Line Probe Assays (LiPAs) (Inno-Lipa HBV DRv2 and Inno-Lipa HBV DRv3, lnnogenetics, Belgium). A total of 71 subjects under follow-up for chronic hepatitis B and receiving lamivudine (LVD) therapy for one year or longer at the Hacettepe University Faculty of Medicine, Department of Internal Medicine, Gastroenterology Unit were included in the study with informed consent. Male to female ratio and mean age was noted as 47/24 and 43 ± 15.8 (age range: 13-71) years, respectively. Twenty samples with low HBV DNA levels (mean: 204.6 lU/ml) could not be interpreted by SEQ due to insufficient amplification. All samples with a positive consensus PCR were further analysed via LiPAs, as directed by the manufacturer. Thus a total of 51 and 56 samples could be evaluated via SEQ and LiPA assays, respectively. In 13 of the 51 (25.5{\%}) samples by SEQ and in 9 of 56 (16{\%}) samples by LiPAs, primary and compensatory mutations associated with resistance were identified. Multiple mutations that comprise LI 8OM + M204l in four and L18OM + M204V in one sample and single mutations (M204l) in three samples were identified by SEQ. In one sample which had multiple mutations associated with LVD resistance single mutations (S202G, N236T) associated with entecavir resistance and in two other such samples mutations associated with adefovir resistance were detected by SEQ. Also, in three samples aminoacid substitution at position rt215 (Q-S) as alone and in one sample with multiple mutations were observed via SEQ. In five of nine samples primary and compensatory multiple mutations (LI 80M + M204I in one sample, L80I + L18OM + M204I in two samples, L80I/V + M204I in one sample) and primary single mutations associated with LVD resistance (M204I/V) in four samples were detected by Inno-Lipa HBV DRv2. Two different mutations (G202, ILFM184) were observed in two samples with multiple mutations associated LVD resistance via Inno-Lipa HBV DRv3. However, mutation at position rt184 was evaluated as a weak positive. Any mutation associated with adefovir resistance was not detected by LiPA. As a result, SEQ and LiPAs displayed comparable performances for the detection of HBV drug resistance mutations. We suggested that for the evaluation of discordant results, it should be better to test consecutive serum samples.",
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AU - Aydoǧan, Sibel

AU - Ergünay, Koray

AU - Balaban, Yasemin

AU - Alp, Alpaslan

AU - Şmşek, Halis

AU - Tatar, Gonca

AU - Hascelik, Gülşen

AU - Dürdal, U. S.

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KW - Dna sequencing

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