title: Performance of hepatitis B surface antigen tests with the first WHO international hepatitis B virus genotype reference panel.
abstract: BACKGROUND
  Standardization of hepatitis B surface antigen (HBsAg) tests is indispensable for consistent quality and comparability. Ideally, the assays should detect all known hepatitis B virus (HBV) genotypes equally well.
  
  
  OBJECTIVE
  Development of an HBV genotype reference panel for HBsAg assays representing the most prevalent HBV subgenotypes to address commutability and traceability of the heat-inactivated 2nd WHO International Standard (IS) for HBsAg in relation to native HBsAg and to HBV genotypes.
  
  
  METHODS
  An HBV panel of 15 non-inactivated lyophilized specimens representing the subgenotypes A1, A2, B1, B2, C2, D1-D3, E, F2, and H was evaluated in parallel to the IS by 15 laboratories using 19 different HBsAg tests and tree unitages. The virus content of the samples was reduced by ultracentrifugation and dilution to <2×10(4) IU HBV DNA/mL.
  
  
  RESULTS
  Twenty-two qualitative and 6 quantitative data sets were evaluated. Overall, the results demonstrated consistent detection of HBV genotypes by the majority of tests with a mean potency variability relative to the IS of 36%. Some assays showed significant genotype-dependent differences in analytical sensitivity. Some tests were more sensitive with the IS, others less. On average, one IU HBsAg corresponded to 0.88±0.20 ng HBsAg protein.
  
  
  CONCLUSIONS
  The panel was accepted by the WHO as the "1st International Reference Panel for HBV genotypes for HBsAg-based assays". The panel is a helpful complementation to the IS to validate HBV genotype specific analytical test sensitivities.
authors.affiliation: Section of Molecular Virology, Paul-Ehrlich-Institut, Langen, Germany. Michael.Chudy@pei.de
authors.forename: M
authors.initials: M
authors.lastname: Chudy
authors.forename: H
authors.initials: H
authors.lastname: Scheiblauer
authors.forename: K-M
authors.initials: KM
authors.lastname: Hanschmann
authors.forename: J
authors.initials: J
authors.lastname: Kress
authors.forename: S
authors.initials: S
authors.lastname: Nick
authors.forename: U
authors.initials: U
authors.lastname: Wend
authors.forename: C
authors.initials: C
authors.lastname: Schüttler
authors.forename: C M
authors.initials: CM
authors.lastname: Nübling
authors.forename: W H
authors.initials: WH
authors.lastname: Gerlich
mesh_terms: D019411:Clinical Laboratory Techniques / Q000379:methods* / Q000592:standards*; D005838:Genotype; D006509:Hepatitis B / Q000175:diagnosis* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics*; D006801:Humans; D059021:Laboratory Proficiency Testing; D012680:Sensitivity and Specificity; D014944:World Health Organization
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: HBV diagnostics; HBV genotype diversity; HBV genotype sensitivity; HBsAg; HBsAg unitages; Reference preparations