The UK's blood donations are now being universally tested for hepatitis B in an effort to reduce the risk of hepatitis B virus (HBV) in the UK's blood supply, following an investigation that looked into two cases, one of which was fatal, of tainted blood.
A recently published report from November 2021 revealed the recommendation for universal testing for anti-hepatitis B core (anti-HBc) antigen for all blood donors in an effort to reduce the risk occult hepatitis B infection (OBI). A spokesperson for the NHS Blood and Transplant (NHSBT) said that currently, 90% of donor blood is being tested, and they expect to reach 100% over the next few weeks.
The report, published by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) OBI working group, proposed that universal anti-HBc testing should initially be done for all donors, and then only for new donors who had not donated within the previous 2 years.
The recommendations were the result of an investigation that was prompted by two cases of probable transfusion-transmitted HBV infection in 2018, one of which was fatal. Enquiries revealed the two cases, which were traced back to red cell transfusions, had originated with donors who had OBI that had not been picked up by routine screening .
Although HBV is not common in the UK, it is one of the most frequently detected infections in blood donors in England, according to NHS Blood and Transplant (NHSBT). In the UK, all blood donations are tested for hepatitis B surface antigen (HBsAg) since 1972, and for HBV DNA using the highly sensitive nucleic acid amplification testing (NAT) technique in mini pools of 24 donations (a compromise between cost and detection sensitivity) since 2009. The UK currently only tests a small subset of donors for anti-HBc.
The 19-member working group, chaired by Will Irving, professor of virology at the University of Nottingham, included virologists, epidemiologists, microbiologists, a health economist, a hepatologist, lay members, and representatives of the DHSC, Public Health England, and NHSBT.
DNA From Past Infection Lingers for Life
Anti-HBc is a marker of either active or past infection with HBV, and the team said that "any individual who has had past HBV infection may harbour viral DNA in their hepatocytes for their lifetime; such virus may replicate and result in release of infectious viral particles into the blood stream". Anti-HBc is detectable in blood samples in about 80-90% of OBI cases.
OBI was defined as having undetectable levels of HBsAg, despite the presence of HBV DNA and detectable levels of anti-HBc. The committee noted that, although individuals have been reported with OBI in the absence of anti-HBc (seronegative OBI) in countries where HBV is endemic, there is little data about the prevalence of seronegative OBI in countries with low levels of HBV infection, though the number is thought to be very low.
Most occult HBV cases are infected with a replication competent virus, their report said, and "the true rate of transfusion-associated transmission of OBI likely approaches 60%". However, markers detectable by standard HBV screening of blood donations are frequently absent, and may be identifiable risk factors for HBV infection in the donors. Moreover, HBV infections in blood recipients are completely asymptomatic in around 50% of cases.
In the UK, 27 blood donors were identified with OBI from 2009 to 2018; 25 of them during donation screening and the remaining two as a result of lookback investigations following reported transfusion-associated cases. Most donors with OBI were males (n=22, 81%), over 45 years of age (n=20, 74%), and repeat donors (n=18, 67%). Exposure history was identified for 21 donors, 18 of whom were born in countries where HBV is endemic.
Follow up of all recipients of blood from OBI donors from 2009 to 2015 discovered 74 donations; among the recipients, 33 were deceased, 33 tested negative for HBsAg and HBV DNA, two had evidence of past HBV infections, and six were not followed up.
The committee said that although the lookback data were "reassuring", its collection was "laborious" and "transmission could easily be missed in circumstances when not all recipients can be contacted". Enhanced lookback was reintroduced in 2019, they noted.
'Unacceptable' Risk from Occult Infection in Donors
The committee examined two published experimental models from South Africa and Australia to estimate the residual risk of an HBV-infected donation from an OBI donor entering the blood supply, yielding residual risk estimates of 7.9 and 41.3 per million donations, respectively. These contrasted with the considerably lower residual risk from donors who were within the window period of an acute HBV infection, at 0.87 per million donations. The estimated residual risk of infection of HBV from OBI donors was "unacceptable", the group said.
The panel then appraised two options for changing the current screening strategy to mitigate the risk from OBI donors:
- Reduced pool NAT, increasing test sensitivity by reducing the size of donation congeries tested from the current pool of 24 donations to either a smaller pool of four to eight donations, or to individual testing of donations
- Introducing universal testing for anti-HBc antigen, initially for all donors, then only for new donors and those who had not donated within the previous 2 years
Lastly, the group assessed the costs and benefits of the two possible OBI testing strategies in terms of the total 10-year costs to UK blood services covering testing, operational impacts (including the additional staff, equipment and space required), and donor loss, versus the number of additional OBI detections and remaining residual risk (number of non-detections of OBI), combining these to reach an estimate of the cost per additional OBI detection with each strategy.
Anti-HBc Testing Would Detect Most OBI Donors
Modelling assumed that not all OBI donors would be detected by reducing the size of the NAT mini pool, as even with individual donation testing, the viral load for HBV in the blood of some donors would still be below the level of detection. In contrast, most if not all OBI donors would be detected by introducing anti-HBc testing.
The committee calculated that under the South African experimental model of residual risk, reducing the mini-pool size for HBV NAT to four to eight donations would cost an extra £250,000, and individual donation testing an additional £1 million, per infected donation identified. In the Australian model, these costs would be £45,000 or £200,000, respectively.
Introducing anti-HBc testing would cost an additional £63,000 per additional infected donation detected under the South African model, or £12,000 under the Australian model. However, the majority of the cost and benefit would be in the first phase of testing of all donors.
SaBTO concluded that introduction of anti-HBc testing would be "the most effective way of reducing risk" and "more cost effective than reducing the HBV NAT pool size", even if not all anti-HBc positive potential donors would have OBI at the time of testing. However, high levels of anti-HBs are associated with a considerably reduced risk of transmission of OBI and "it would be reasonable to allow such donors to continue to donate if they had anti-HBs levels exceeding 100 IU/L", the group said, though this should be "at the discretion of individual blood services".
Significant but Short-Term Impact on Donor Supply
The committee acknowledged that if donations from all anti-HBc-positive donors were deferred, this would have "a significant, short-term impact on the donor supply" and would require further investigation of donors identified with or at risk of OBI.
In addition: "Given the uncertainties in the data used to provide a cost/benefit analysis, the group recommends that the strategy is reviewed after 12 months of implementation when additional [data] will be available." A revised residual risk estimate and a more complete economic appraisal will then be possible.
The anti-HBc test was introduced from 31 May 2022 and is gradually being rolled out. Earlier this year SaBTO member Dr Su Brailsford, consultant in epidemiology & health protection for NHSBT, said: "We expect that only a small number of donors will have had previous hepatitis B infection, however, these donors will no longer be eligible to donate."
She added: "The UK has one of the safest blood supplies in the world – there is less than one in a million chance of current screening tests missing a newly acquired infection."