title: Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples.
abstract: BACKGROUND
  Natural variation and mutations in the envelope protein (S) of hepatitis B virus can translate into HBsAg variants no longer detectable by conventional HBsAg assays.
  
  
  OBJECTIVE
  The aim of the study was to assess the performance of 13 commercial assays currently used for screening and clinical analysis of HBsAg variants.
  
  
  METHODS
  The limit of detection (LOD) for each assay was established using two reference standards (WHO HBsAg 00/588 and the SFTS French reference). Sensitivity was evaluated using different panels. Panel 1 included 25 recombinant HBs variants at three concentrations, panels 2 and 4 included 8 recombinant HBsAg variants and 9 wild-type proteins (genotypes A-F), respectively, panel 3 included 16 natural HBsAg variants.
  
  
  RESULTS
  LODs ranged from 0.011 to 0.095 IU/ml with the WHO standard, and from 0.021 to 0.326 ng/ml with the French reference. The overall percentage of positive signals using HBsAg variants ranged from 62.9% to 97.9%. Three substitutions: T123, D144A and G145, were negative at all concentrations with at least one assay.
  
  
  CONCLUSIONS
  Our findings show that, although they fulfil CE requirements for analytical sensitivity (LODs below 0.13 IU/ml), HBsAg assays may vary in their capacity to detect HBsAg variants. This limit in diagnosis performance should encourage the health regulatory agencies to include HBsAg variant panels in the evaluation process.
authors.affiliation: National Reference center for Hepatitis B and C in Blood Transfusion, Institut National de la Transfusion Sanguine, Paris, France. aservant@ints.fr
authors.forename: Annabelle
authors.initials: A
authors.lastname: Servant-Delmas
authors.forename: Mélanie
authors.initials: M
authors.lastname: Mercier-Darty
authors.forename: Thoai Duong
authors.initials: TD
authors.lastname: Ly
authors.forename: Françoise
authors.initials: F
authors.lastname: Wind
authors.forename: Chakib
authors.initials: C
authors.lastname: Alloui
authors.forename: Camille
authors.initials: C
authors.lastname: Sureau
authors.forename: Syria
authors.initials: S
authors.lastname: Laperche
mesh_terms: D001782:Blood Donors; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000097:blood* / Q000175:diagnosis; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D057230:Limit of Detection; D009154:Mutation; D011933:Reagent Kits, Diagnostic / Q000592:standards; D012015:Reference Standards; D012680:Sensitivity and Specificity
chemical_list: D006514:Hepatitis B Surface Antigens; D011933:Reagent Kits, Diagnostic