Probable transmission of hepatitis E virus (HEV) via transfusion in the United States

Abstract

Background: Hepatitis E virus (HEV) can inapparently infect blood donors. To assess transfusion transmission of HEV in the United States, which has not been documented, a donor-recipient repository was evaluated.

Study design and methods: To identify donations that contained HEV RNA and were linked to patient-recipients with antibody evidence of HEV exposure, we assayed samples from the Retrovirus Epidemiology Donor Study (REDS) Allogeneic Donor and Recipient repository that represents 13,201 linked donations and 3384 transfused patients. Posttransfusion samples, determined to contain IgG anti-HEV by enzyme-linked immunosorbent assay, were reassayed along with corresponding pretransfusion samples for seroconversion (incident exposure) or at least fourfold IgG anti-HEV increase (reexposure). HEV-exposed patients were linked to donations in which HEV RNA was then detected by reverse-transcription quantitative polymerase chain reaction, confirmed by transcription-mediated amplification, and phylogenetically analyzed as subgenomic cDNA sequences.

Results: Among all patients, 19 of 1036 (1.8%) who had IgG anti-HEV before transfusion were reexposed; 40 of 2348 (1.7%) without pretransfusion IgG anti-HEV seroconverted. These 59 patients were linked to 257 donations, 1 of which was positive by reverse-transcription quantitative polymerase chain reaction and transcription-mediated amplification. Plasma from this donation contained 5.5 log IU/mL of HEV RNA that grouped with HEV genotype 3, clade 3abchij. The patient-recipient of RBCs from this donation had a greater than eightfold IgG increase; however, clinical data are unavailable.

Conclusions: This is the first report of probable HEV transmission via transfusion in the United States, although it has been frequently observed in Europe and Japan. Additional data on the magnitude of the risk in the United States are needed.

FIGURE 1.. Testing algorithm for patient-recipient and donation samples from the RADAR repository.

We assayed post-transfusion specimens for IgG anti-HEV and, for those with reactive results, tested corresponding pre-transfusion specimens in subsequent assay-runs. Each specimen-pair that yielded preliminary evidence of HEV exposure during the sampling interval, as manifested by seroconversion or by ≥ 3.5-fold increase in IgG anti-HEV S/CO value, was re-assayed on a single ELISA plate. We then assayed for HEV RNA in donations that were linked to patients who had single-plate confirmed seroconversion or ≥ 4-fold increase of IgG anti-HEV concentration. Finally, we determined and analyzed partial nucleotide sequences of any detected HEV RNA in donation samples.

FIGURE 2.. Phylogenetic tree of a 530-nucleotide segment of HEV ORF1 from 31 reference-taxa and a RADAR donation.

This tree is a rectangular phylogram with an HEV genotype 5 outgroup. Bootstrap values, as per cent of 100 re-samplings, are indicated by italicized numerals near branch-points. Reference-sequences ^, are designated by country; host; collection-year (b, before the earlier of GenBank deposition or publication; c, circa, the midpoint in a range of possible years); GenBank accession number, in parentheses; [WHO Std], 1st WHO International Standard for Hepatitis E Virus RNA Nucleic Acid Amplification Techniques-Based Assays; and clade assignment by Smith et al. ^, or, with asterisk, Vina-Rodriguez et al. . All recognized human subtypes of genotypes 1, 2, 3, and 4 are represented except 3d, for which only ORF2 sequences have been reported , and 3ra that primarily represents rabbits and for which there is one reported human-strain sequence that includes the pertinent ORF1 segment ^,. “USA human c2001 RADAR donor” designates sequence from this study. Largest numerals and brackets indicate genotypes; numeral 3 followed by letters indicate proposed monophyletic groups . Bar indicates genetic distance.