Transfusion-transmitted hepatitis E: What we know so far?

Table 2 Hepatitis E virus ribonucleic acid prevalence in donor, only studies include more than 1000 study subjects are included

Ref.	Country	Initial screening method	Number of donations screened	Number positive donations	Prevalence (95%CI)	HEV genotype: n/N	Median (range) viral load, IU/mL	Outcome of recipient
Europe
Fischer et al[45], 2015	Austria	RT-PCR (plasma pool of 96 samples) with 95% LOD 11.6 IU/mL	58915	7	0.012%	3: 7/7	(2200 to 290000)	N/A
Vercouter et al[46], 2019	Belgium	RT-PCR (plasma pool of 6 samples) with 95% LOD 18.6 IU/mL	38137	7	0.018%	N/A	(153 to 8710)	N/A
Harritshøj et al[47], 2016	Denmark	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	25637	11	0.043% (0.02% - 0.07%)	3 (in 2 samples)	13 (unquantifiable to 920)	(1) Look-back testing was performed in 7 recipients; all were tested negative for HEV RNA and anti-HEV IgM; (2) No recipient developed transaminitis; and (3) One patient had strongly positive anti-HEV IgG assay which may indicate recent HEV infection or secondary immune response by HEV re-exposure.
Gallian et al[48], 2014	France	RT-PCR (plasma pool of 96 samples) with 95% LOD 23 IU/mL	53234	22	0.045% (0.043%-0.047%).	3c: 5/14; 3f: 8/14; 3 1/14	(468 to 5155800)	N/A
Westhölter et al[49], 2018	Germany	RT-PCR (plasma pool of 24 samples) with 95% LOD 18.6 IU/mL	18737	23	0.123%	3: 6/7	(120 to 11200000)	(1) Retrospective analysis of 4 viremic donors showed that they were HEV-positive in previous donations; (2) In 3 donors, testing of the previously donated blood in pools of 24 samples failed to identify viremic donations but were tpositive in unpooled samples; (3) Fourteen recipients had received HEV RNA positive blood products; (4) One immunosuppressed recipient tested positive for HEV RNA, developed acute on chronic liver failure, and died; and (5) One immunocompetent recipient developed acute self-limited episode of hepatitis E
Dreier et al[50], 2018	Germany	RT-PCR with 95% LOD 4.7 IU/ml for FFP, platelet concentrates, and RBC supernatant; 95% LOD 8.9 IU/mL for RBCs.	235524	182	0.077%	3: 4/4	(< 25 to 69.4)	(1) Nine viremic donations were transfused to 6 different recipients; (2) Two recipients were immunocompromised (heart transplantation and leukemia); (3) Two recipients died shortly after transfusion for reasons other than HEV infection; and (4) None of the other 4 recipients developed acute HEV infection or had detectable HEV RNA / anti-HEV IgG
Corman et al[51], 2013	Germany	RT-PCR (plasma pool of 96 samples mixed in metapools of 20)	93955	14	0.015%	3: 14/14	(3.1 to 4.8 Log10 IU/mL)	N/A
Vollmer et al[52], 2012	Germany	RT-PCR (plasma pool of 48 samples) with 95% LOD 4.7 IU/ml	16125	13	0.081%	3: 13/13	(13 to 68100)	N/A
Baylis et al[53], 2012	Germany	RT-PCR (plasma pool of 96 samples) with 95% LOD 250 IU/mL	18,100	4	0.022%	3	(3.26 to 5.35 log10 copies/mL)	Donations screened positive for HEV were excluded from pharmaceutical production
O'Riordan et al[54], 2016	Ireland	TMA assay with 95% LOD 5.5 IU/mL	24985	5	0.020% (0.0065%-0.0467%)	3: 3/3	(10 to 44550)	N/A
Spreafico et al[55], 2020	Italy	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	9726	1	0.010% (0.00%-0.06%)	N/A	N/A	N/A
Spada et al[56], 2018	Italy	RT-PCR, plasma pool and sensitivity varies according to anti-HEV IgG and IgM status	10011	0	N/A	N/A	N/A	N/A
Hogema et al[57], 2015	Netherlands	RT-PCR (plasma pool of 96 samples) with 95% LOD 38.4 IU/mL with the EasyMag extraction method and 10.3 IU/mL using Qiagen extracts	59474	41	0.069%	3c: 15/17; 3f: 2/17	N/A	N/A
Slot et al[58], 2013	Netherlands	RT-PCR (plasma pool of 48 or 480 samples) with 95% LOD 25 IU/mL	40176	13	0.032%	3: 16/17	(< 25 to 470000)	N/A
Grabarczyk et al[59], 2018	Poland	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	12664	10	0.079% (0.043%-0.145%)	3i: 2/3; 3c: 1/3	(16 to 6586 in 4 patients with positive results in qPCR)	N/A
Rivero-Juarez et al[60], 2019	Spain	RT-PCR (plasma pool of 8 samples) with sensitivity 670 IU/mL	11313	4	0.035% (0.01%-0.09%)	3: 4/4	(10788 to 2000000)	(1) Five patients received transfusions from HEV-infected donors; and (2) None of them showed an increase in alanine aminotransferase levels after transfusion
Sauleda et al[61], 2015	Spain	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	9998	3	0.030% (0.01%-0.09%)	3f (in 1 sample)	(250 to 2755)	N/A
Baylis et al[53], 2012	Sweden	RT-PCR (plasma pool of 96 samples) with 95% LOD 250 IU/mL	95835	12	0.013%	3	(3.20 to 5.68 log10 copies/mL)	Donations screened positive for HEV were excluded from pharmaceutical production
Harvala et al[62], 2019	United Kingdom	RT-PCR (plasma pool of 24 samples) with 95% LOD 18.6 IU/mL	1838747	480	0.026%	3c: 112/149; 3e: 21/1493f: 12/149; 3a: 1/149; 2 distantly related to 3h, and 1 clustered distantly with 3a	883 (1 to 3230000)	N/A
Thom et al[63], 2018	United Kingdom	RT-PCR (plasma pool of 24 samples)	94302	38	0.040%	3: 10/10	N/A	N/A
Hewitt et al[64], 2014	United Kingdom	RT-PCR (plasma pool of 24 samples)	225000	79	0.035%	3: 79/79	3900 (50 to 2.37 × 106)	(1) Forty-three patients who had received blood components from HEV-infected donors were followed up; (2) The overall transmission rate was 42% (18 of 43 exposed patients); (3) One recipient developed clinical hepatitis and 4 recipients developed asymptomatic transaminitis; and (4) Four heavily immunosuppressed patients had delayed (37-38 wk) seroconversion or no antibodies detected
Cleland et al[65], 2013	United Kingdom	Nested PCR (plasma pool of 24 samples) with 95% LOD 201 IU/mL	43560	3	0.0069%	3: 3/3	N/A	N/A
North America
Delage et al[66], 2019	United States	RT-PCR on individual samples with 95% LOD 18.6 IU/mL	50724	3	0.0059%	3: 2/3; genotyping was unsuccessful in 1 patient	(23 to 1420)	N/A
	Canada		50765	11	0.022%	3 (in 1 sample)	(< 10 to 3080)
Roth et al[67], 2017	United States	RT-PCR (plasma pool of 96 samples) with 95% LOD 18.6 IU/mL	128021	4	0.003%	3a: 3/3	(3.0 to 3.8 log IU/mL)	N/A
Stramer et al[68], 2016	United States	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	18829	2	0.011% (0.0018%-0.351%)	N/A	14 IU/mL in one sample	N/A
Xu et al[69], 2013	United States	RT-PCR (plasma pool of 7 to 8 samples) with 95% LOD 400 IU/mL and nested PCR with 95% LOD 200 IU/mL	1939	0	N/A	N/A	N/A	N/A
Baylis et al[53], 2012	United States	RT-PCR (plasma pool of 96 samples) with 95% LOD 250 IU/mL	51075	0	N/A	N/A	N/A	N/A
Asia
Wen et al[70], 2018	China	RT-PCR on individual plasma	5345	15	0.281%	One 4h, another one clustered between genotype 2 and 4i	N/A	N/A
Tsoi et al[71], 2019	Hong Kong	RT-PCR with 95% LOD 7.89 IU/mL	10000	2	0.02%	4 (in 1 sample)	N/A	N/A
Katiyar H et al[72], 2018	India	RT-PCR (plasma pool of 3 samples) with LOD 100 IU/mL	1799	0	N/A	N/A	N/A	N/A
Minagi T et al[73], 2016	Japan	RT-PCR (plasma pool of 50 or 500 samples) with 95% LOD 152 IU/mL	620140	36	0.0058%	3: 36/36	(< 1.69 to 7.22 log10 copies/mL)	N/A
Intharasongkroh et al[74], 2019	Thailand	RT-PCR (plasma pool of 6 samples) with 95% LOD 53.5 IU/mL	30115	26	0.086%	3: 6/6	N/A	N/A
Others
Hoad et al[75], 2017	Australia	TMA (plasma pool of 6 samples)	74131	1	0.0013%	N/A	180	N/A
Shrestha et al[76], 2016	Australia	TMA assay on individual plasma with 95% LOD 7.9 IU/mL	14799	1	0.0068% (0.0002%-0.0376%	3	15000	N/A
Hewitt et al[77], 2018	New Zealand	RT-PCR (plasma pool of 8 to 12 samples)	5000	0	N/A	N/A	N/A	N/A
Maponga et al[78], 2020	South Africa	TMA assay on individual plasma with 95% LOD 7.9IU/mL	10000	1	0.01%	3	79000	All donations from donors with active HEV infection were discarded

CI: Confidence interval; FFP: Fresh frozen plasma; HEV: Hepatitis E virus; Ig: Immunoglobulin; LOD: Limit of detection; RBC: Red blood cells; RNA: Ribonucleic acid; RT-PCR: Real time polymerase chain reaction; TMA: Transcription mediated amplification.