Independent report

Executive summary: hepatitis E virus transmission by blood transfusion - review of current screening effectiveness

Published 8 December 2025

The Hepatitis E Virus (HEV) Working Group was established in October 2020 to re-examine the effectiveness of current HEV screening of blood and platelet (apheresis) donors and to advise on whether it provides sufficient mitigation of transmission risk. HEV screening is currently performed by nucleic acid testing (NAT) for HEV ribonucleic acid (RNA) in pools of 24 or 16 alongside NAT for human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and HCV).

HEV testing is applied universally to all whole blood, platelet and plasma donations, as well as donors of organs and tissues. The effectiveness or otherwise of current HEV screening was reviewed in the light of a recent report of the death of an immunocompromised patient who became infected with HEV from transfusion of a platelet unit (see reference 1). The donation contained enough virus to be infectious but insufficient to be detected by current screening for HEV. Through donor lookback, further missed donations that were potentially infectious or demonstrated to be infectious were described.

The study group has discussed and reported back on the following areas requested in the remit for the working group provided by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO):

• the testing or donor selection strategies that are available to reduce HEV transmission risk and whether they are feasible to implement
• the residual risk of HEV transmission from red cells, platelets and plasma screened by current methodology
• the cost of introducing assays with increased sensitivity, and whether their use is cost effective by conventional health economic metrics
• to discuss and resolve each of these matters with the working group and make a recommendation to SaBTO on the benefit and value of changes to HEV testing strategy

The summary of the working group discussions and decisions is as follows.

Dietary exposure to HEV from uncooked pork is the primary source of HEV infection in the UK, including of blood and organ donors. There is little immediate prospect of HEV infection being reduced or removed from pork production in the UK or elsewhere.

With current screening, it was calculated that the proportion of donations with undetected HEV RNA per year was 0.004% (95% confidence interval (CI) 0.0025% to 0.0059%) for apheresis donations, and 0.003% (95% CI 0.0027% to 0.0034%) for whole blood donations.

The predicted infectivity of blood components depended on their residual plasma content. Plasma content was predicted to range from 33% (apheresis platelets) to 4% for red cells.

The health economic analysis was crucially dependent on several parameters that relate to the health impact of HEV transmission. In 2022 a review of outcomes of infections in recipients from 12 studies between 2014 and 2020 provided information on the proportion of recipients who might develop severe, life-threatening disease on infection and the extent to which persistent infections in the immunocompromised may be effectively treated (see reference 2).

It was estimated that approximately 6 platelet, plasma and red cell recipients are infected per year from donations missed by current screening, with an estimated impact of 5.9 quality-adjusted life years (QALYs) per year.

A QALY is a measure used to assess the value of medical interventions by combining the quantity of life with the quality of life.

A variety of donor selection and alternative testing strategies for HEV screening to reduce transmission risk were considered. The only practical methods available were to:

• increase sensitivity of HEV screening through testing of donation samples in smaller pools or individually
• use platelet additive solution (PAS) to reduce residual plasma volume in platelets

Individual NAT was considered capable of virtually eliminating current residual transmissions of HEV, but at a substantially increased additional testing cost when used for all donations.

The working group acknowledged the predicted benefit of individual NAT but acknowledged the high cost of doing so compared to other medical interventions.

Recommendations for SaBTO

Recommendation 1

The increased cost of testing individual donations for HEV (£11 million per year) was over 60 times greater than its calculated health economic benefit (£176,000) based on a QALY value of £30,000. This economic calculation shows that testing individual donations for HEV RNA is not conventionally cost-effective, and if decisions to implement changes in testing are based purely on this health economic metric, the working group does not recommend any change to current screening practice.

Recommendation 2

The working group recognises the existence of less easily quantified factors such as reputational damage to the blood services if further incidents of HEV transmission occur with continuation of the less sensitive testing in ‘minipools’. Consequently, we advise that SaBTO evaluates risk tolerability as it applies to HEV screening and the extent to which conventional cost effectiveness calculations can be applied in the area of transfusion safety.

Recommendation 3

SaBTO should develop a communications plan for the report, for example by writing to relevant royal colleges to raise awareness of HEV infection in the management of patients. Early diagnosis and initiation of appropriate treatment may substantially reduce HEV-associated morbidity and mortality. Some members of the HEV Working Group co-authored a review in 2023 on maintaining the microbiological safety of the UK blood supply (see reference 3) that may contribute to greater awareness of transfusion-transmitted infections.

Recommendation 4

Each year, SaBTO should review the reported incidence of HEV infections in the wider community using epidemiological data provided by the UK Health Security Agency (UKHSA), and NAT positivity rates in UK blood and platelet donors. Changes in HEV incidence can be evaluated against the economic model developed in this report and the QALY costs can be reviewed. Large increases in HEV incidence should prompt a re-evaluation of HEV testing strategies by the UK blood services - NHS Blood and Transplant (NHSBT), the Scottish National Blood Transfusion Service (SNBTS), the Welsh Blood Service (WBS) and the Northern Irish Blood Transfusion Service (NIBTS).

Recommendation 5

Evaluation of current testing should be mindful of donation testing strategies by blood services in other countries and their HEV transmission risk evaluations.

Recommendation 6

A review of the effect of potential changes in the parameters used in the current report should be undertaken in 5 years. Those changes might include:

• progress towards HEV elimination in pork production
• potential changes in NAT testing methods, pool sizes for other targets and associated costs
• the effectiveness of PAS in reducing the plasma content of apheresis platelets
• the development of pathogen inactivation (PI) technologies, their costs and potential use for red cell components
• increasing knowledge of the outcomes of HEV infection, better identification of susceptible individuals, potential improved antiviral treatments for HEV and greater clinical awareness by clinicians of HEV as a post-transfusion complication

References

1. Harvala H and others. Fulminant transfusion-associated hepatitis E virus infection despite screening, England, 2016 to 2020. Emerging Infectious Diseases 2022: volume 28, pages 1805 to 1813

2. Cheung CKM and others. Transfusion-transmitted hepatitis E: what we know so far. World Journal of Gastroenterology 2022: volume 28, pages 47 to 75

3. Neuberger J and others. Challenges for maintaining the microbiological safety of the UK blood supply. Clinical Medicine (London) 2023: volume 23, issue 2, pages 151 to 156