Research Article
HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients

https://doi.org/10.1016/j.jhep.2018.02.031Get rights and content

Highlights

  • HEV viraemia was detected in 23 out of 18,737 blood donors (0.12%).

  • HEV viraemia was prolonged for more than four months in an asymptomatic blood donor.

  • Eating undercooked pork meat is a major risk factor for HEV infection.

Background & Aims

Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe.

Methods

All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire.

Results

Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2.

Conclusions

Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection.

Lay summary

The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.

Introduction

HEV infections are present worldwide.1 Consumption of pork meat has been considered to be the major source of HEV Genotype (GT) 3 infections in Europe. In addition to zoonotic transmission, blood products were shown to be a potential source of acute and chronic HEV infection in industrialised countries.[2], [3] The anti-HEV seroprevalence rate in Europe, depicting the number of people previously exposed to HEV, varies largely depending on the region and the assay used.4 A high seroprevalence rate of 30% was found in healthy German individuals using the sensitive Wantai anti-HEV IgG assay.5 In addition to serological studies, blood donors were tested for HEV viraemia by PCR in various European studies, and rates of HEV positivity from 1:726 to 1:3,333 have been determined.[6], [7], [8], [9], [10], [11] The largest of these studies was conducted in the UK. In this study, 225,000 blood donations were tested in pools of 24 samples by an in-house assay, and 79 specimens tested positive for HEV PCR (1 out of 2,850). The likelihood of developing clinically relevant hepatitis E after transfusion of an HEV-contaminated blood product was 42%,10 while in a Japanese study, 50% of recipients of HEV-contaminated blood products developed HEV infection.12 Since it became apparent how frequently HEV was found in blood products, routine testing of blood products has been discussed controversially in many European countries. In the vast majority of these countries, HEV screening has not been implemented, while authorities in the UK, Ireland, and the Netherlands decided to test all blood products for HEV.13 The aim of the present study was to determine the prevalence of blood-borne HEV infections at our academic tertiary care centre in Northern Germany and to evaluate whether routine HEV testing of blood products should be performed.

Section snippets

Routine screening

Routine screening of all blood donations for HEV RNA was implemented at our centre, the University Medical Center Hamburg-Eppendorf, in October 2016. Here, we present data from a three-day preliminary testing phase in September 2016 in addition to 8-month routine screening data following the implementation of screening (October 2016 to May 2017). Identical protocols were applied in preliminary and routine screening phases. The study was in line with the recommendations of the local ethics

Identification of HEV RNA-positive blood donors through prospective screening

From October 2016 to May 2017, 18,737 blood donations were prospectively tested for HEV viraemia at the blood transfusion service of the University Medical Center Hamburg-Eppendorf. HEV viraemia was detected in 23 asymptomatic blood donors (D1–D23), resulting in an HEV RNA prevalence of 0.12% (1:815) in this cohort (Table 1; Fig. 1). At the time of blood donation, only 3 out of 23 HEV RNA-positive blood donors presented with detectable anti-HEV IgG and IgM; one donor tested positive for

Discussion

Here, we report the first study describing the experience with prospective routine HEV screening of blood donations at a German academic tertiary care centre. The authors of individual case reports and small retrospective case series have studied the severity of transfusion-associated HEV infections.[2], [3], [12] Furthermore, a number of prospective studies have evaluated the frequency of HEV RNA-positive blood donations in numerous European countries,[6], [7], [8], [9], [10] and a

Financial support

The authors received no financial support to produce this manuscript.

Conflict of interest

ML reports personal fees from lectures and advising for Roche Diagnostics, and grants from validation of laboratory-developed-test assays on the cobas 6800 (Roche), outside the submitted work. SP reports personal fees from Roche Diagnostics and MSD, outside the submitted work.

Please refer to the accompanying ICMJE disclosure forms for further details.

Authors’ contributions

DW, ML, and SP developed the concept of the study and wrote the manuscript. DW and SP coordinated the follow-up of HEV viraemic blood donors. ML, SG, and NF were responsible for the sequencing. ML, SP, UD, JB and JH coordinated the collection, pooling, and testing of blood samples. JH, DW, FA, MR, TH, and SP supervised the data collection and reviewed the drafts. MMA, AWL, JSW and BG revised the manuscript for important intellectual content. All authors reviewed the final manuscript.

References (26)

  • S. Pischke et al.

    Blood-borne hepatitis E virus transmission: a relevant risk for immunosuppressed patients

    Clin Infect Dis

    (2016)
  • V. Mallet et al.

    Transmission of hepatitis E virus by plasma exchange: a case report

    Ann Intern Med

    (2016)
  • Cited by (74)

    • Transplantation Pathology

      2023, MacSween's Pathology of the Liver, Eighth Edition
    • Chronic hepatitis E: Advancing research and patient care

      2022, Journal of Hepatology
      Citation Excerpt :

      Transfusion-transmitted acute HEV infection was first indicated in Japanese studies in 2004,47 and chronic HEV infection acquired via blood transfusion was reported later in Japanese liver transplant recipients.48 Subsequently, a series of cases were reported in Europe, particularly in immunocompromised patients, several of whom developed chronic infection.49,50 These cases have been associated with the transfusion of various blood components including fresh frozen plasma, red blood cell samples, platelet preparations and pooled granulocytes.51

    View all citing articles on Scopus

    These authors contributed equally and are both first authors.

    These authors contributed equally and share senior authorship.

    View full text