Source: Hollinger FB. Transfusion 2008 48:1001-1026
How will the introduction of NAT affect the window period for detection of HBV?
The implementation of individual donation HBV NAT will reduce the infectious window period for HBV from approximately 38 days to approximately 24 days.
What is occult HBV infection (OBI)?
Acute HBV infection is self-limiting in approximately 97% of immunocompetent adults leading to recovery and immunity.
However, in 3% of cases, individuals remain chronically infected (i.e. carrier state), usually testing HBsAg positive and anti-HBc positive.
Some of these chronically infected individuals can, however, have very low and/or intermittently detectable levels of HBV DNA and, on testing, are found to be HBsAg negative, anti-HBc positive, HBV DNA positive or negative and anti-HBs positive or negative. This is known as occult HBV infection (OBI).
What do we know about OBI in blood donors?
The prevalence of OBI in blood donors varies markedly by region. One study of Asian blood donors (Liu C et al 2006) quotes a median prevalence of 1% with a range of 0 to 4.6% of donors.
The HBV DNA viral load is generally low and therefore intermittently detectable.
In a review of transfusion-transmitted HBV, Candotti & Allain (2009) analysed available data from a number of international studies. The synthesized data for cases of confirmed HBV transfusion-associated transmission showed that the rate of HBV transmission by components collected from donors in the window period of acute HBV infection was greater than those collected from donors with OBI (81% versus 19% respectively).
References:
- Liu CJ, Chen DS, Chen PJ. Epidemiology of HBV infection in Asian blood donors: emphasis on occult HBV infection and the role of NAT. J Clin Virol 2006; 36 Suppl 1: S33-44.
- Candotti D, Allain JP. Transfusion-transmitted hepatitis B virus infection. J Hepatol. 2009 Oct;51(4):798-809.
With the introduction of HBV NAT, is the Blood Service likely to find existing blood donors who have OBI?
The Australian Red Cross Blood Service HBV screening algorithm combining universal HBsAg screening and a ”history of hepatitis” (HOH) protocol has substantially reduced the risk of transfusion transmitted HBV infection in Australia, with the current estimated residual risk being 1 in 739,000. This residual risk benchmarks well against other comparable international blood service.
All donors must complete a comprehensive medical questionnaire and sign a declaration form relating to risk factors for transfusion transmissible infections. Each donor also participates in a confidential interview to determine their eligibility to donate.
Potential donors who declare symptoms or a history of hepatitis undergo additional testing (i.e. anti-HBc and anti-HBs and, if necessary, HBV DNA testing) to further determine their eligibility to donate.
This HOH protocol does partially address the risk of having a donor with OBI. However, as individuals who have HBV infection may be asymptomatic (50-70% of cases), it is possible that a donor with OBI may not to be identified through the donor questionnaire and confidential interview and the additional testing will not be performed.
The addition of HBV NAT will increase the probability of detecting donors with OBI. It is estimated that, following implementation of HBV NAT, a small number of potential new donors and existing donors with OBI may be identified.
What are the implications of identifying existing donors with OBI?
All donors identified as having OBI would need to be notified of their test results, counseled and referred for further medical management.
Blood component recall and lookback investigations would need to be undertaken for any previous donations provided by existing donors who are subsequently identified as having OBI.
Why doesn’t the Blood Service routinely perform anti-HBc screening on all donations?
The Blood Service does screen potential donors for anti-HBc if they have indicated past exposure to hepatitis. However, the test is not used routinely for all donations because of its relatively high rate of false reactivity. This would result in the unacceptable loss of many healthy donors whose donations are reactive in the test but who are not infectious.
Are other countries screening for anti-HBc?
Other countries that have a higher prevalence of HBV in the community than Australia such as the USA, Canada and France screen donors for anti-HBc.
How will the implementation of NAT for HBV affect the residual risk estimates for transfusion transmitted HBV?
The following table shows the change in infectious window period (WP), the percentage of window period closure and the residual risk estimates for HBV following the implementation of HBV NAT.
The window period closure of 37.6% for HBV will reduce the residual risk of transfusion transmitted HBV from 1 in 739,000 to less than 1 in 1 million.
|
HBV | HBsAg | No NAT | 38 | | 1 in 739,000 |
ULTRIO | 1 | 24 | 37.6% | Less than 1 in 1 million |
How does the Australian residual risk estimate for transfusion transmitted HBV compare internationally?
The current Blood Service residual risk estimate for transfusion transmitted HBV (based on 2007/08 data) of approximately 1 in 739,000 is lower than comparable international blood services:
- USA 1 in 205,000 - 488,000 (Zou et al 2009)
- Canada 1 in 153,000 (O’Brien et al 2007)
- Germany 1 in 360,000 (Houfar et al 2008)
- France 1 in 640,000 (Pillonel and Laperche 2005)
- UK 1 in 600,000 (Soldan et al 2005)
The introduction of HBV NAT will further reduce the Australian residual risk estimate to less than 1 in 1 million.
What was the process for the introduction of the HBV NAT?
The Blood Service actively monitors emerging technologies and the donor screening approaches used across the industry.
The Blood Service has previously undertaken a cost/benefit evaluation regarding the implementation of HBV NAT which recommended that routine implementation of hepatitis B NAT would be of benefit provided the testing was able to be undertaken on single donations given the estimated prevalence in Australia. This has now been made possible with the recent availability of fully automated NAT testing platforms.
The Blood Service has since participated in an international study evaluating the two commercially available automated NAT platforms which both provide HBV NAT.
A business case and formal tender process was completed and, in line with government funding approval, the implementation planning to introduce this technology is now well advanced.
The Blood Service is working closely with the Therapeutic Goods Administration (TGA) to ensure that the testing is introduced at the earliest opportunity. It is anticipated that testing will be provided for the Australian blood supply from mid 2010 with all fresh blood components supplied by the Blood Service being tested by HBV NAT by early September 2010.
When will all fresh blood components be tested by HBV NAT?
From early September 2010, all red cells and platelets supplied by the Blood Service will have been tested for HBV DNA using the NAT triplex assay.
As frozen clinical plasma (i.e. fresh frozen plasma, cryoprecipitate and cryodepleted plasma) have a longer shelf-life, management of these components during the transition period will be more complex. However, the Blood Service also aims to be able to supply only HBV NAT tested clinical plasma components from early September 2010 and is implementing a number of strategies to facilitate this.
Approved Health Providers (AHPs) are advised to review their current inventory holdings of clinical plasma components, as well as their inventory management practices, to enable a more rapid turnover of product during the transition period. It is recommended that AHPs hold a maximum of two months' supply of clinical plasma in the lead-up to the commencement of HBV NAT testing. It should be noted that the Blood Service inventory holdings of clinical plasma will be increased during this period to compensate for the reduced AHP stock holdings.
The Blood Service will be working closely with the Therapeutic Goods Administration (TGA), the National Blood Authority (NBA), governments and the clinical community to provide the optimal outcome with respect to blood component inventory management during the transition period.
What about plasma derived products?
Plasma derived products such as immunoglobulin products, albumin solutions and coagulation factor concentrates undergo two dedicated pathogen inactivation and/or removal steps during their manufacture which have been validated to result in multiple log reductions in potential pathogens.
Additionally, the fractionation process includes physical separation using precipitation and chromatography which also contribute to non-specific reduction of viruses and other pathogens.
No confirmed transmissions of viral agents have occurred from products used in Australia since introduction of effective, dedicated pathogen inactivation and removal steps.
Based on the fact that there is no change to the risk profile of plasma-derived products, the recommended framework for the introduction of HBV NAT testing is as follows:
- Retrospective HBV NAT testing of retained samples from plasma pools need not be performed on the basis that it would not be useful, because the level of HBV DNA is almost certain to be below the current level of sensitivity of the test.
- Prospective HBV NAT testing of manufacturing pools that include only HBV NAT tested donations will be introduced to ensure consistency with HIV and HCV testing procedures.
- Recall and lookback for plasma-derived products are not indicated based on the current risk evaluation.