Time for change – Addressing the risk of occult hepatitis B in blood donations
Doctors Emma Wakins and Heli Harvala.
A recent analysis of hepatitis B infections in blood donors has resulted in a review of the current screening strategy for blood donations in the UK. Recommendations to further reduce the risk of hepatitis B transmission via blood transfusion are anticipated later on in Autumn 2021.
Hepatitis B is a serious liver infection, caused by the Hepatitis B Virus (HBV) that is spread through blood and body fluids. Hepatitis B infection can become a chronic condition for some people, which means that it lasts more than six months. Having a chronic Hepatitis B infection can increase a persons risk of developing liver failure, liver cancer or cirrhosis — a condition that permanently scars of the liver. HBV infection is a major public health problem worldwide and an ongoing risk to blood safety. Although HBV is not commonly found amongst people in the UK, it is still one of the most frequently detected infections in blood donors in England.
NHS Blood and Transplant (NHSBT) has been testing blood donations for the surface HBV antigen (HBsAg) since 1972, and for HBV DNA using the highly sensitive nucleic acid amplification testing (NAT) technique since 2009. Additional testing for the HBV core antibody (anti-HBc) is performed on donations from blood donors reporting a relevant history including past HBV infection, or jaundice of unknown cause.
It has been estimated that two recent HBV infections will be missed by testing every year in the UK. This is because the amount of virus is so little at the beginning of an infection that it cannot be detected by current methods. However, this estimate does not consider how likely it is that an occult (silent) hepatitis B infection (OBI) may be missed. This is a form of chronic HBV infection where low levels of HBV DNA can be intermittently detected in a blood sample but the level of HBsAg is undetectable by the tests currently available. Anti-HBc is detectable in blood samples in about 80–90% of OBI cases. Blood donations that are HBsAg-negative and anti-HBc positive can transmit HBV via transfusion, although transmission rates might be as low as 5% and depend on factors such as viral load (amount of virus) and the volume of the component transfused.
In our recent study1, we collected epidemiological*, virological, and genotyping information on 655 positive HBV cases identified in blood donors in England during the ten-year period from 2009 to 2018. The estimated risk of non-detection and likely transmission of OBI, was calculated using two separate models from Australia and South Africa. The estimate was compared to our data available on HBV transmission via blood transfusion to the recipients.
The overall HBV prevalence was 6.9 per 100,000 donors, with a higher prevalence in donors of Asian or Black African ethnicity. 598 of the HBV infections were chronic, 32 were acute and 25 were occult infections. Most donors (83%) with chronic and 58% of donors with occult infections were born in Eastern Europe, Africa, or Asia. Acute infections were largely seen in UK-born donors. Genotyping revealed five HBV genotypes (A–E), reflecting donor ethnicity and country of birth.
Between 2009 and 2018, 40 cases of possible transfusion transmitted HBV, were investigated by NHSBT. From these, transmission was confirmed in one case where an early acute HBV infection was missed and probable in two other cases, both linked to donors with OBI. It is often difficult to confirm HBV transmission from OBI cases due to low levels of virus in the blood, which makes it challenging to determine the viral sequence. Furthermore, retrospective exercises are also often unable to prove or disprove transmission due to a lack of recorded information about the fate of the donations and insufficient follow-up data on the recipients.
We calculated the average risk of OBI transmission to be 3.9–6.5 per million donations collected, which is four times higher than the calculated HBV window period residual risk.2 The residual risk of non-detection of OBI was 17.5 per million using the Australian model and 7.9 per million using the South African model based on data for 2016 and 2018. NAT screening on individual donations, rather than on pools of donations could potentially reduce the annual transmissions from an estimated 7 cases to less than two, but anti-HBc screening would be required to eliminate that risk. Although most cases of OBI can be identified by sensitive individual NAT screening, evidence in the literature indicates that around 10% of OBI cases will still be missed unless anti-HBc screening is used as well. Universal anti-HBc screening of blood donations would reduce or eliminate the risk of OBI not being detected. However, without extensive reference testing, it would also lead to a reduction in the donor base due to false reactivity.
OBI remains a risk to the safety of the blood supply, as well as to individuals. Identification of these occult infections would benefit transfusion recipients and would benefit blood donors by making them aware of the HBV reactivation risk if they were to become immunodeficient (where a person’s immune system is compromised or entirely absent and is no longer able to fight infectious diseases/cancer). Despite the very low number of actual reported HBV transmissions in England, the results of our analysis have prompted the UK’s Advisory Committee of the Safety of Blood, Tissues and Organs (SaBTO) to consider the costs vs the benefits of revising the testing requirements for blood donations. SaBTO is due to make recommendations later this year, which will ensure that the UK continues to minimise any risks to the safety of blood components for transfusion.
*Epidemiology is the study and analysis of the distribution, patterns and determinants of health and disease conditions in defined populations.
2. Safe supplies 2018: monitor, inform, progress. NHSBT/PHE Epidemiology Unit. Access epidemiology reports.
If you would like to learn more, you can read the full publication.
R&D Blog Co-Authors
Emma Watkins (PA to Dr. Heli Harvala) and Dr. Heli Harvala (NHSBT Principal Investigator)
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