However, in rare cases HBV can reach concentrations in the blood by which reduction procedures cannot be challenged. measure in addition to existing methods or measures will have very poor cost effectiveness. Therefore each country needs to perform its own calculation based on the countrys own epidemiology, resources, political and public awareness of the risks, in order to choose the correct and most cost-efficient measures. Ideally, each country would make decisions regarding implementation of additional blood safety measures in the context of both the perceived benefit and the allocation of overall health care resources. strong class=”kwd-title” Keywords: hepatitis B virus, transfusion-transmitted infection, HBsAg, anti-HBc, NAT Introduction Since the milestone introduction of hepatitis B surface antigen (HBsAg) testing in 1969, the risk of transfusion-transmitted hepatitis B virus (TTHBV) has steadily decreased, thanks to the development of increasingly more sensitive HBsAg assays; the adoption in some countries of hepatitis B core antibody (anti-HBc) screening; improved donor selection, including Ozenoxacin nonremunerated intrinsically motivated blood donors; HBV vaccination programs; and finally the introduction of hepatitis B virus (HBV) nucleic acid testing (NAT) in minipools (MP) or later on as individual (ID) testing. Several different approaches can be envisaged to reduce the risk of TTHBV. These vary according to the prevalence of HBV in a certain region; the extent to which a population is already vaccinated against HBV; the local economic situation; the availability of specific technical equipment; the availability of suitable donors; and the level of safety that is requested by the corresponding society. Based on these considerations, different algorithms can be foreseen, such as the sole serological approach with HBsAg; testing for HBsAg and anti-HBc; serology in combination with a less sensitive NAT (minipools); or on the other hand a highly sensitive ID NAT-only approach. Within these considerations it can be argued whether NAT should be Ozenoxacin dropped and antigen/antibody tests developed for more cost-effective screening strategy, or whether HBsAg testing could be dropped if an adequate sensitive NAT system was adopted. All these possible approaches have advantages and disadvantages and will be discussed in the present review. In the end, a balance between donor loss, economic reasons, required safety, and donor counseling has to be found for every country or region and an appropriate algorithm has to be defined. HBsAg testing A unique feature of the HBV life cycle is the production of large amounts of free HBsAg in the form of particles and filaments in vast excess to intact DNA-containing virions. This phenomenon makes HBsAg a very sensitive and useful marker of HBV infection, and HBsAg testing became the first-line screen for HBV. Over the past 40 years, the sensitivity of these tests has increased by 2 log10 as the technology advanced from crude immunological techniques to reverse passive hemagglutination (RPHA) and enzyme immunoassays (EIA), including enzyme-linked immunosorbent assays (ELISA), and the current assays now employing chemiluminescence (CLIA) detection. There are more than 40 commercially available HBsAg assays currently in use around the world. Nevertheless, comparative studies have highlighted key differences in analytical detection sensitivities for HBsAg from wild type, mutant, and specimens of different genotypes among commonly used EIAs.1C6 The most sensitive assays detect HBsAg levels 0.1 ng/mL, but significantly less sensitive methods with detection limits 1 ng/mL still continue to be used worldwide. The CLIA sensitivity of 0.08 ng/mL corresponds to 102C267 HBV DNA IU/mL as determined by NAT quantification of seroconversion panels, but can only be applied to the window period (WP) phase.7,8 Several other deficiencies with HBsAg assays have become apparent in recent years. During the 59 day window period (45C50 days for most Ozenoxacin sensitive assays)8C10 for HBV infection, HBsAg tests are not sensitive enough. Likewise in the early convalescence phase (core window) of HBV infection Ozenoxacin acute phase as well as in chronic HBV infections very low levels of HBsAg Mouse monoclonal to TrkA are often present, which are not detected by the routinely used HBsAg assays.11C25 Mutations associated with conformational and hydrophobic changes within and outside the immunogenic major hydrophilic region (MHR) of the S antigen, the main target for capture antibodies in commercial HBsAg assays, often lead to reduced synthesis or secretion of HBsAg. Such changes may account solely or in conjunction with other factors for the failure of immunoassays to detect HBsAg.5,26C31 There have been several reports on HBV escape mutants which were not detected by.
However, in rare cases HBV can reach concentrations in the blood by which reduction procedures cannot be challenged