New Strategies for Blood Donor Screening for Hepatitis B Virus

Abstract

Serologic testing for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV core antigen (anti-HBc) has historically been the foundation of blood screening, while HBV nucleic acid testing (NAT) was recently developed to detect HBsAg-negative, anti-HBc-negative blood units donated during early acute infection. Comparison data on seroconversion panels using HBsAg assays of varying sensitivities and pooled- or single-sample NAT, along with viral load estimates corresponding to HBsAg assay detection limits, have provided information on the theoretical benefits of NAT relative to HBsAg. Model-derived estimates have generally been predictive of the yields of DNA-positive, HBsAg-negative window period blood units detected in a number of studies from Europe, Japan, and the US. Studies indicate that the added benefit of pooled-sample NAT is relatively small in areas of low endemicity, with greater yields in areas highly endemic for HBV. Single-sample NAT would offer more significant early window period closure and could prevent a moderate number of residual HBV transmissions not detected by HBsAg assays; however, no fully automated single-sample HBV NAT systems are currently available.Even single-sample HBV NAT may not substitute for anti-HBc screening, as indicated by studies of donors with isolated anti-HBc who have extremely low DNA levels undetectable by standard single-sample NAT and who have been associated with transfusion-transmitted HBV. Moreover, HBsAg testing may still be needed even in the setting of combined anti-HBc and NAT screening. HBsAg-positive units from donors in the chronic stage of infection may contain very low or intermittently detectable DNA levels that single-sample NAT would miss. Although such donors are usually anti-HBc reactive and would be interdicted by anti-HBc screening, some lack anti-HBc. Extensive parallel testing will be needed to determine whether single-sample NAT in combination with anti-HBc might be sufficient to detect all the infectious donors currently interdicted by HBsAg testing. In countries that do not screen for anti-HBc, HBsAg testing would be the only means of detecting donations from chronically infected individuals with low/intermittently detectable DNA, since even single-donor NAT would not identify these potentially infectious blood units. In the future, the current fully automated HBsAg assays may incorporate significant sensitivity improvements, and automated single-sample HBV NAT may become a reality. Each country will need to develop its blood screening strategy based on HBV endemicity, yields of infectious units detected by different serologic/NAT screening methods, and cost effectiveness of test methods in ensuring blood safety.

Prevalence of hepatitis B and hepatitis C virus infection in repeatedly transfused thalassemics in a tertiary care hospital in eastern India

“…Blood screening using the viral antigen and nucleic acid amplification tests (NAT) can reduce the window periods of HIV, hepatitis B virus and hepatitis C virus infections substantially. 25 Estimates of the risk of blood-borne infections are essential for monitoring the safety of blood supply and the impact of new screening tests. Blood transfusion, a lifesaving modality, can be made safer by the introduction of the NAT for screening of blood units for HIV, hepatitis B and hepatitis C viruses and it can be made cost-effective by Analysing multiple samples together.…”

Seroprevalence of HIV, hepatitis C and hepatitis B in multitransfused thalassemics

“…[3] Estimates of the risk of bloodborne infections are essential for monitoring the safety of blood supply and the impact of new screening tests. Blood transfusion, a life saving modality, can be made safer by the introduction of the NAT for screening of blood units for HIV, Hepatitis B and Hepatitis C viruses and it can be made cost-effective by pooling samples.…”

Need for Quality Assurance Program of Donor Screening Tests

“…HBV NAT in donor screening has been introduced in the Finland and Netherland since 2009 and in Korea since 2011. Although theoretical benefits of HBV NAT relative to HBsAg has been proven through comparison data on seroconversion panels as been using HBsAg assays of varying sensitivities, benefit of pooled-sample NAT is relatively small in areas of low endemicity, with greater yields in areas highly endemic for HBV [11] . Japan is the first country introducing HBV NAT as a donor screening test in 1999, now using 20-MP since 2004.…”