1 Introduction

Human Herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is the causative agent of Kaposi sarcoma (KS). It is globally distributed but pathogenic in a small proportion of individuals, particularly in immunocompromised. KS occurs 200 times more frequently in solid organ transplant (SOT) recipients than in the general population [1]. HHV8 infection in SOT is also linked to other diseases like Multicentric Castleman Disease, Primary Effusion Lymphoma, and KSHV Inflammatory Cytokine Syndrome [2]. HHV8 is mainly transmitted horizontally via saliva; other routes include vertically, sexually, through blood and transplant transmission [3]. In SOT recipients, infections can arise from reactivation or donor transmission, with donor-derived infections often being severe and rapidly progressing [4]. KS typically presents with skin abnormalities, but disseminated infections can present heterogeneously, sometimes lacking skin involvement, complicating diagnosis [2]. Serostatus information of the donor and recipient promotes early recognition of infection. Global HHV8 seroprevalence varies significantly, with the highest rates in Africa (up to 80%) and much lower rates in the USA and Northern Europe (below 10%) [3]. Rates also differ based on risk groups. In the Netherlands, a seroprevalence of 39%–65% among men who have sex with men and 5% among repeat male blood donors has been reported [5]. Screening for HHV8 in donors is not common in the Netherlands, but changing donor and recipient demographics necessitate reevaluation of screening strategies.

This pilot study aimed to determine the current HHV8 seroprevalence among SOT donors and recipients at the University Medical Center Groningen to estimate the risk of donor positive/recipient negative (D+/R−) mismatches and to reconsider our current screening strategy.

2 Methods

A retrospective pilot study was conducted using stored serum samples from SOT donors and recipients at the UMCG. The study included transplant procedures between April 2022 and September 2023. HHV8 serology testing was performed on pretransplant samples of 144 donors and 145 recipients using the Indirect Fluorescence Assay (IFA) for Human Herpesvirus 8 Lytic IgG antibody (Biocell) [6]. More than 60% of the samples were from the day before or on the day of transplantation, 20% within 2 months prior to transplantation and 20% had a longer interval. Samples were considered positive if deemed so by at least two independent lab technicians. Since donor sera are stored anonymously, donors and recipients could not be matched.

3 Results

Table 1 shows the baseline characteristics of the recipients only, since donors are anonymous. Of the recipients 66% were male, the mean age was 57 years, and the distribution of transplant types reflected the proportions of SOT in our center, mostly kidney, followed by liver and lung.

Among the recipients, 10.3% (15/145) tested positive for HHV8 Lytic IgG antibody. When weak positives were included, seropositivity was 17.9%. No significant differences were found in age or gender distribution among the different IFA result categories. Among the donors, 2.8% (4/144) tested positive for HHV8 Lytic IgG antibody. Including weak positives, 10.4% tested positive. For details of test results, see Table 2. With a seroprevalence of 2.8% in donors and 10.3% in recipients, the calculated risk of a D+/R− mismatch is 2.5%.

4 Discussion

The study found a higher-than-expected seroprevalence of 10.3% among SOT recipients, compared to 2.8% among donors. This discrepancy aligns with other studies showing higher seroprevalence in recipients than donors [6-12]. This may be attributed to differences in sociodemographic factors such as older age and increased risk of exposure to HHV8 among recipients. Additionally, the physical trauma associated with the transplant process may trigger reactivation of KSHV/HHV8, leading to elevated antibody levels and resulting in a positive classification of the recipient's sample.

The observed seroprevalence indicates an estimated risk of a 2.5% chance of a donor-positive/recipient-negative (D+R−) combination, with and even lower risk of symptomatic disease. Literature reports symptomatic infection rates from 0% in D+R+ combinations [7, 12] to up to 38% in D+R− combinations [6-12]. A recent large study by Mularoni et al. [12] found HHV8 transmission in 45% of D+R− cases, with a 26.5% rate of related disease and 8.2% mortality.

Given these data, is our policy of not screening for HHV8 still justifiable? Current guidelines do not support universal HHV8 screening due to lack of evidence. Screening options include serology before transplantation and posttransplant HHV8 DNA monitoring. An international survey [4] showed varying screening practices, with higher screening habits in high-prevalence areas.

The study's limitations include its pilot nature, small sample size, and lack of donor sociodemographic data. Given our results and fewer than one clinical HHV8 infection per year out of a total of 235 SOTs in 2022 in our center, screening does not seem warranted. However, due to globalization, seroprevalence is constantly subject to changes and we need to monitor this from time to time. Further multicenter research is recommended to better assess HHV8-related disease risk and screening benefits.

Ethics Statement

The Board of Directors of the University Medical Centre Groningen (UMCG) and the Central Ethics Review Board Non-WMO studies (CTc UMCG) have approved the conduct of the study on January 19, 2024.

Consent

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.