NHSBT is reliant on the General Data Protection Regulation Article 6(1)(e)—Performance of a public task. Under Article 9(2)(h), (i), and (j), NHSBT is allowed to use patient identifiable information for service evaluation and safety monitoring without the consent of patients.

The introduction of universal screening was considered in the context of the relevant UK epidemiology for this zoonotic infection and its clinical impact on immunocompromised patients. The incidence of asymptomatic acute HEV infection observed in the UK blood donor population was around 1 in 2,850 donors when a large study was conducted in 2012/13 [3] with no significant changes in the immediate subsequent years and a decline from 2017, mirroring the epidemiology in the UK general population [4]. A gradual drop in incidence has been observed over more recent years, with 1 in 4,347 being the approximate figure for blood donors in 2021 [5]. Interestingly, the yield from deceased organ donor screening has been showing a different pattern, with one case of acute HEV being identified per 536, 1,682 and 1,797 donors tested in 2020, 2021, and 2022, respectively. The reason for this is not entirely clear, and not only do we continue to detect HEV viraemia in deceased donors, but we have also seen an increase in incidence during the COVID-19 pandemic. The demographics of acutely infected donors reflects the epidemiology of the general UK population, with more cases seen in men in the >50 year old age group [4]. The numbers tested are low, on average 1,600 to 1,800 potential donors per year, hence the number of identified infected donors is small, but significant; the screening strategy introduced in the UK in late 2017 has led to the identification of 20 recipients who have benefited from monitoring and tailored intervention to avoid ultimate liver damage due to late diagnosis. The approach hereby described ensured no transplant-related chronic infections were missed in the organ recipients since donor screening was initiated. Many more infections acquired through consumption of contaminated food are likely to be missed, so information and awareness amongst patients and healthcare professionals remains important.

Donor-derived HEV infection has been infrequently described, with scarce publications available in the literature [6–8]. Without organ donor screening and post-transplant recipient surveillance for HEV RNA positivity, there is a real possibility of under recognition of infection of donor origin; diagnosis of chronic HEV infection many months or years after transplantation does not necessarily trigger look back investigations. It is acknowledged however, that apart from further contribution from transfusion-associated infections, the dietary route remains the main route of acquisition of zoonotic HEV genotypes. In the setting of significant immunocompromise, absence of significant inflammatory responses with normal or mildly abnormal liver enzymes may not trigger testing, particularly in the early post-transplant period. Familiarity with local epidemiology and need to include HEV in testing panels, where appropriate, can address some of the issues with under ascertainment and late diagnosis.

There is no definition of infectious dose in the context of an infected organ being used for transplantation, and presence of viable virus within the graft is theoretically sufficient to pose a transmission risk; no data exist to suggest thresholds of transmission based on measured plasma viral load in the donor and indeed, low plasma loads in our donor cohort were associated with transmission through not only liver, as would be expected, but also kidneys (Table 1). Risk of transmission is of course multifactorial, but some observations from this cohort are worthy of mention. As viable virus will be present in the liver, viral load in plasma during early acute and early resolving infection in the donor cannot be used to stratify risk of transmission through this organ; as seen in our cases, low level VL in the order of 10^2 IU/mL resulted in transmission through the liver but not through kidneys from the same donor. Transmission via an infected liver graft with undetectable viral RNA in plasma has been described [6]. Determinants of transmission and control of infection have not been defined but both viral and host factors are expected to play a role; this includes the net immune status of recipients as regards to control of viral infections. Previously described recipient characteristics that are linked to progression to HEV chronicity include lower lymphocyte count and exposure to tacrolimus [9]; detailed variables are also being collated for this cohort.

Where local epidemiology, risk-benefit and cost analysis justify testing of donors and/or recipients, it is important to note that recipient follow up needs to be extended and should not be shorter than 12 weeks, as late RNA detection in non-liver recipients does occur. Conversely, in liver recipients, with the graft being the main site of virus replication, viremia becomes detectable within days from transplant.

Guidance on the management of HEV in solid organ transplantation [1, 10], advise to monitor for 3 months from the point of diagnosis, unless otherwise clinically indicated, allowing time to assess the infection status and possible control without anti-viral treatment. Previous studies have indicated that approximately 33% of acutely infected solid organ transplant recipients clear HEV infection spontaneously within this time frame, with the remaining progressing to chronicity [9, 11]. Of note, subjects in the studied cohort had had their transplants years before acquiring HEV infection, a scenario that differs from when infection is acquired at the time of transplant, as the net state of immunosuppression and other parameters may differ between these time points. Whether a similar proportion of solid organ transplant patients undergoing acute donor-derived infection would have the same outcome, is unknown. In the UK cohort, only one out of the 15 individuals who tested positive for HEV RNA in plasma went on to become negative within 3 months from diagnosis of acute hepatitis. None of the patients who were either monitored beyond 3 months from the date of first positive result or who had a delayed diagnosis of HEV infection made beyond the first 3 months from transplantation, managed to control the infection and went on to receive ribavirin. This suggests that in the setting of donor-derived infection, and in contrast to infection acquired later in the post-transplant period, earlier treatment may be an approach that deserves consideration; further accrual of data from more cases may help clarifying this. Logically, this gap in knowledge and practice stems from the fact that risk of exposure through the transplanted graft can only be considered where donor screening is in place; given the variable incidence of HEV genotype 3 infection, this is a practice limited to certain regions where the epidemiology justifies such an approach. This puts countries where screening takes place, in an obligatory position to monitor the impact of the chosen strategy, follow up outcomes and use the data to inform policy and guidance.