No abstract

Background and ObjectivesThis study was conducted by the International Consortium for Blood Safety (ICBS) to identify high-quality test kits for detection of hepatitis B virus (HBV) surface antigen (HBsAg) for the benefit of developing countries.Materials and MethodsThe 70 HBsAg test kits from around the world were evaluated comparatively for their clinical sensitivity, analytical sensitivity, sensitivity to HBV genotypes and HBsAg subtypes, and specificity using 394 (146 clinical, 48 analytical and 200 negative) ICBS Master Panel members of diverse geographical origin comprising the major HBV genotypes A-F and the HBsAg subtypes adw2,4, adr and ayw1-4.ResultsSeventeen HBsAg enzyme immunoassay (EIA) kits had high analytical sensitivity <0·13 IU/ml, showed 100% diagnostic sensitivity, and were even sensitive for the various HBV variants tested. An additional six test kits had high sensitivity (<0·13 IU/ml) but missed HBsAg mutants and/or showed reduced sensitivity to certain HBV genotypes. Twenty HBsAg EIA kits were in the sensitivity range of 0·13–1 IU/ml. The other eight EIAs and the 19 rapid assays had analytical sensitivities of 1 to >4 IU/ml. These assays were falsely negative for 1–4 clinical samples and 17 of these test kits showed genotype dependent sensitivity reduction. Analytical sensitivities for HBsAg of >1 IU/ml significantly reduce the length of the HBsAg positive period which renders them less reliable for detecting HBsAg in asymptomatic HBV infections. Reduced sensitivity for HBsAg with genetic diversity of HBV occurred with genotypes/subtypes D/ayw3, E/ayw4, F/adw4 and by S gene mutants. Specificity of the HBsAg assays was ≥99·5% in 57 test kits and 96·4–99·0% in the remaining test kits.ConclusionDiagnostic efficacy of the evaluated HBsAg test kits differed substantially. Laboratories should therefore be aware of the analytical sensitivity for HBsAg and check for the relevant HBV variants circulating in the relevant population.

Seventeen HBsAg assays, in use in the European market (CE-marked), were assessed for their diagnostic sensitivity using 38 commercially available seroconversion panels, and for their analytical sensitivity with the HBsAg ad and ay standards of the Paul-Ehrlich-Institut (PEI). In addition, the ability to detect HBsAg mutants was investigated by means of 21 recombinant HBsAg mutant samples and 5 natural mutants. Analysis of seroconversion data revealed that there were marked differences in the sensitivity among the CE-marked HBsAg assays. Differences in the window period between the most and the least sensitive assays were up to 2 weeks. Analytical sensitivities of the investigated assays ranged from 0.009 to 0.05 PEI-U/ml for HBsAg ad standard (relating to approximately 0.018 to 0.100 IU/ml of the 2nd WHO HBsAg standard) and 0.012 to 0.11 PEI-U/ml for the ay standard. Clinical and analytical sensitivities were basically correlated. The capacity to detect mutant HBsAg forms was influenced by the assay format and the properties of the monoclonal antibodies used for coating of the solid phase or in the conjugate. While some assays detected all mutants others exhibited weaknesses especially in recognising HBsAg mutations affecting loop 2 of the HBsAg a-determinant. The results obtained with the recombinant mutants were largely confirmed by the investigation of clinical samples. The study gives a broad overview of the current state of the art of about 70% of the HBsAg assays currently available in Europe. The overall sensitivity has not been improved further since 1995 when the most sensitive assay was introduced into the market. In addition, detection of HBsAg mutants seems problematic with several assays. It is concluded that there is potential to improve clinical sensitivity and mutant recognition of HBsAg assays.

No abstract

No abstract