1887

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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.053041-0
2013-12-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/12/2729.html?itemId=/content/journal/jgv/10.1099/vir.0.053041-0&mimeType=html&fmt=ahah

References

  1. Beck J., Nassal M. 2007; Hepatitis B virus replication. World J Gastroenterol 13:48–64[PubMed] [CrossRef]
    [Google Scholar]
  2. Bozdayi G., Türkyilmaz A. R., Idilman R., Karatayli E., Rota S., Yurdaydin C., Bozdayi A. M. 2005; Complete genome sequence and phylogenetic analysis of hepatitis B virus isolated from Turkish patients with chronic HBV infection. J Med Virol 76:476–481 [View Article][PubMed]
    [Google Scholar]
  3. Chen R. Y., Edwards R., Shaw T., Colledge D., Delaney W. E. IV, Isom H., Bowden S., Desmond P., Locarnini S. A. 2003; Effect of the G1896A precore mutation on drug sensitivity and replication yield of lamivudine-resistant HBV in vitro. Hepatology 37:27–35 [View Article][PubMed]
    [Google Scholar]
  4. Cho E. Y., Choi C. S., Cho J. H., Kim H. C. 2001; Association between hepatitis B virus X gene mutations and clinical statusin patients with chronic hepatitis B infection. Gut Liver 5:70–76 [View Article]
    [Google Scholar]
  5. Choi J. W., Ahn S. H., Park J. Y., Chang H. Y., Kim J. K., Baatarkhuu O., Kim Y., Han K. H., Chon C. Y. 2009; Hepatitis B e antigen-negative mutations in the precore and core promoter regions in Korean patients. J Med Virol 81:594–601 [View Article][PubMed]
    [Google Scholar]
  6. D’Aurelio M., Vives-Bauza C., Davidson M. M., Manfredi G. 2010; Mitochondrial DNA background modifies the bioenergetics of NARP/MILS ATP6 mutant cells. Hum Mol Genet 19:374–386 [View Article][PubMed]
    [Google Scholar]
  7. Eriksson N., Pachter L., Mitsuya Y., Rhee S. Y., Wang C., Gharizadeh B., Ronaghi M., Shafer R. W., Beerenwinkel N. 2008; Viral population estimation using pyrosequencing. PLOS Comput Biol 4:e1000074 [View Article][PubMed]
    [Google Scholar]
  8. Fung J., Lai C. L., Seto W. K., Yuen M. F. 2011; Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B. J Antimicrob Chemother 66:2715–2725 [View Article][PubMed]
    [Google Scholar]
  9. Homs M., Buti M., Quer J., Jardí R., Schaper M., Tabernero D., Ortega I., Sanchez A., Esteban R., Rodriguez-Frias F. 2011; Ultra-deep pyrosequencing analysis of the hepatitis B virus preCore region and main catalytic motif of the viral polymerase in the same viral genome. Nucleic Acids Res 39:8457–8471 [View Article][PubMed]
    [Google Scholar]
  10. Kidd-Ljunggren K., Miyakawa Y., Kidd A. H. 2002; Genetic variability in hepatitis B viruses. J Gen Virol 83:1267–1280[PubMed]
    [Google Scholar]
  11. Koike K., Takada S. 1995; Biochemistry and functions of hepatitis B virus X protein. Intervirology 38:89–99[PubMed]
    [Google Scholar]
  12. Livezey K. W., Negorev D., Simon D. 2000; Increased chromosomal alterations and micronuclei formation in human hepatoma HepG2 cells transfected with the hepatitis B virus HBX gene. Mutat Res 18:163–178[PubMed] [CrossRef]
    [Google Scholar]
  13. Locarnini S. 2008; Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure. Hepatol Int 2:147–151 [View Article][PubMed]
    [Google Scholar]
  14. Lok A. S., Zoulim F., Locarnini S., Bartholomeusz A., Ghany M. G., Pawlotsky J. M., Liaw Y. F., Mizokami M., Kuiken C. Hepatitis B Virus Drug Resistance Working Group 2007; Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology 46:254–265 [View Article][PubMed]
    [Google Scholar]
  15. Mahtab M. A., Rahman S., Khan M., Karim F. 2008; Hepatitis B virus genotypes: an overview. Hepatobiliary Pancreat Dis Int 7:457–464[PubMed]
    [Google Scholar]
  16. Margeridon-Thermet S., Shulman N. S., Ahmed A., Shahriar R., Liu T., Wang C., Holmes S. P., Babrzadeh F., Gharizadeh B. other authors 2009; Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients. J Infect Dis 199:1275–1285 [View Article][PubMed]
    [Google Scholar]
  17. Osborn M. K., Lok A. S. 2006; Antiviral options for the treatment of chronic hepatitis B. J Antimicrob Chemother 57:1030–1034[PubMed] [CrossRef]
    [Google Scholar]
  18. Papatheodoridis G. V., Hadziyannis S. J. 2001; Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat 8:311–321[PubMed] [CrossRef]
    [Google Scholar]
  19. Seeger C., Zoulim F., Mason S. W. 2007; Hepadnaviruses. In Fundamental Virology pp. 2977–3013 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lipincott;
    [Google Scholar]
  20. Sheldon J., Rodès B., Zoulim F., Bartholomeusz A., Soriano V. 2006; Mutations affecting the replication capacity of the hepatitis B virus. J Viral Hepat 13:427–434 [View Article][PubMed]
    [Google Scholar]
  21. Smith T. F., Waterman M. S. 1981; Identification of common molecular subsequences. J Mol Biol 147:195–197 [View Article][PubMed]
    [Google Scholar]
  22. Solmone M., Vincenti D., Prosperi M. C. F., Bruselles A., Ippolito G., Capobianchi M. R. 2009; Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen. J Virol 83:1718–1726 [View Article][PubMed]
    [Google Scholar]
  23. Tacke F., Gehrke C., Luedde T., Heim A., Manns M. P., Trautwein C. 2004; Basal core promoter and precore mutations in the hepatitis B virus genome enhance replication efficacy of lamivudine-resistant mutants. J Virol 78:8524–8535 [View Article][PubMed]
    [Google Scholar]
  24. Zoulim F., Locarnini S. 2009; Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology 137:1593–1608, e1–e2 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.053041-0
Loading
/content/journal/jgv/10.1099/vir.0.053041-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error