Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS Ampliscreen HBV test

Kleinman Biomedical Research, Victoria, British Columbia, Canada.
Transfusion (Impact Factor: 3.23). 09/2005; 45(8):1247-57. DOI: 10.1111/j.1537-2995.2005.00198.x
Source: PubMed


The risk of hepatitis B virus (HBV) transmission by blood transfusion (estimated at 1 in 63,000-1 in 205,000 units in the United States) exceeds that of hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Reduction of window-period HBV transmissions through detection of HBV DNA-positive units by minipool nucleic acid testing (MP NAT) would be expected to decrease this risk.
A large multicenter study of the COBAS AmpliScreen HBV test (Roche Molecular Systems) was conducted on minipools of 24 blood donation specimens. The yield of HBV DNA-positive, hepatitis B surface antigen (HBsAg)-negative window-period donations was determined relative to current and newly licensed HBsAg assays. Donors with selected HBV DNA, HBsAg, and anti-hepatitis B core antigen (HBc) results were further evaluated.
The detection rate of window-period units was 1 in 352,451 (95% confidence interval, 1 in 2,941,176-1 in 97,561). Assay specificity was high (99.9964%). HBV DNA was detected in 84 percent of HBsAg-positive, anti-HBc-positive donations by MP NAT and in 94 percent when individual-donation (ID) NAT was added. HBV DNA was detected in 0.03 percent of HBsAg-negative, anti-HBc-positive donations by MP NAT and in 0.41 percent when ID NAT was added.
Implementation of HBV MP NAT will provide an increment in safety relative to HBV serologic screening, similar to that for HCV and in excess of that for HIV. Our data indicate that the implementation of HBV MP NAT would likely interdict 39 HBV window-period units and prevent 56 cases of transfusion-transmitted HBV infection annually. The current data indicate that HBV MP NAT should not lead to discontinuation of anti-HBc testing but that discontinuation of HBsAg testing with retention of anti-HBc testing may be possible.

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    • "The detection of antibodies against hepatitis B core (anti-HBc) alone was used previously as a diagnostic marker [Torbenson and Thomas, 2002], although occult HBV infections with other serological profiles have been identified [Mphahlele et al., 2006; Lukhwareni et al., 2009]. In up to 20% of occult HBV cases, all serological markers are absent [Kleinman et al., 2005]. As current testing algorithms for HBV diagnosis rely on HBsAg detection alone or in combination with antibodies against HBV, occult HBV is undiagnosed frequently. "
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    ABSTRACT: Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations—those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references—were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. J. Med. Virol. 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2014 · Journal of Medical Virology
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    • "As Anti-HBcAb being easier to perform than NAT, Anti-HBcAb core test can't be ruled out under the present scenario. Thus, complete elimination of traditional testing methods in the near future seems to be difficult (Busch MP 2004, Stramer SL, 2005, Kleinman SH et al. 2005). Earlier observations have shown that, Anti-HBcAb screening detects HBsAg EIAnegative HBV-infected donors, at a rate comparable to the estimated residual risk for HBV window-period infections (Kleinman SH et al., 2003) NAT can contribute the strategy of safe blood along with core in specific cases where HBV core is reactive by immunoassay (Figure 3). "
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    ABSTRACT: Aim: To develop algorithm focussed on increasing the availability of blood components & cost effectiveness, without compromising blood safety, in a setup where NAT and serological methodological are available. Background: There is increasing usage of total Anti-HBV Core Antibody (anti-HBcAb) &
    Full-text · Article · May 2013 · Journal of Interdisciplinary and Multidisciplinary Research
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    • "Consequently the incremental cost-effectiveness of NAT is marginal since the safety benefits used in these calculations are restricted to the prevention of transmission of NATonly yields and the cost of NAT testing remains relatively expensive [19]. Recent technical advances might be able to address these limitations [23] [24]. "
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    ABSTRACT: Introduction. In India, family/replacement donors still provide more than 45% of the collected blood. With increasing voluntary blood donation and the still-prevalent infectious diseases in donors, we need to augment transfusion-transmitted infections (TTIs) testing before use. Our study was aimed to know the seroprevalence of TTIs among the donors of Rajasthan and the need for newer technologies like nucleic acid testing (NAT). Materials and Methods. Enhanced chemiluminescence immunoassay (ECi) was used for detection of HBsAg, anti-HIV, and anti-HCV in donor serum. 50% of the blood units which were negative on ECi were randomly selected and subjected to NAT testing for HBV, HCV, and HIV. Results. The total seroprevalence of TTIs is 2.62%. Of the randomly selected donor units negative by ECi, 8 turned out to be reactive on NAT testing: 4 were voluntary and 4 were family/replacement donors. Combined NAT yield (NAT reactive/seronegative) for HIV, HCV, and HBV was 0.034% (1 in 2972 donations). All the 8 reactive samples were positive for HBV DNA. Conclusion. In countries with a high prevalence of TTIs like India there are likely to be a significant number of window period donations that can be identified by NAT which may be implemented in blood centers allover India with serological testing to provide safe blood and cost alone should not be a deterrent to the government and implementing agencies.
    Full-text · Article · Sep 2012
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