Development and evaluation of real-time loop-mediated isothermal amplification for hepatitis B virus DNA quantification: a new tool for HBV management

J Clin Virol. 2008 Apr;41(4):270-6. doi: 10.1016/j.jcv.2007.11.025. Epub 2008 Mar 4.

Abstract

Background: Accurate quantitation of hepatitis B viral load is a critical aspect in screening and monitoring HBV infection.

Objectives: We used loop-mediated isothermal amplification (LAMP) to develop a real-time fluorogenic (RtF-LAMP) protocol to quantitate HBV DNA. Quantitative analysis was obtained by measuring time-to-positive (TTP), a biomarker similar to cycle threshold (Ct) in real-time PCR.

Study design: Sensitivity, specificity, reproducibility, and dynamic range for RtF-LAMP were evaluated using molecular and biological standards. Four hundred and two patient samples were then used to compare the performance of RtF-LAMP to a commercial real-time PCR assay (DaAn Gene Co, China).

Results: The lower detection limit (LDL) of RtF-LAMP by Probit analysis at the 95% detection level was 210 copies/ml, and the dynamic range was 8 orders of magnitude. The conversion factor for results obtained with the RtF-LAMP assay was 1 IU/ml equals to 4.4 copies/ml. Coefficients of variation (CV) reflected low intra-assay and inter-assay variability (4.24-12.11%). In a large number of serum samples, there was excellent an correlation between RtF-LAMP and real-time PCR (R(2)=0.96). There was a good agreement between the two tests except at the detection cutoff of the real-time PCR assay.

Conclusion: Our RtF-LAMP protocol appears to be precise, accurate and rapid. It could be a valuable tool for the detection of HBV in large clinical and epidemiological studies.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Analysis of Variance
  • Base Sequence
  • China
  • DNA Primers / genetics
  • DNA, Viral / blood*
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / isolation & purification*
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Amplification Techniques / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Viral Load / methods*

Substances

  • DNA Primers
  • DNA, Viral