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Record number:
1871
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
Hepatitis E virus (HEV) is a global pathogen that, among humans, is represented by a single serotype with four genotypes. Genotypes 1 and 2 are endemic and responsible for waterborne epidemics. Genotypes 3 and 4 are associated with zoonotic HEV infections, which are transmitted to humans through the consumption of raw or undercooked infectious pork and game products, and very rarely shellfish, or by contact with infected animals. HEV genotypes 3 and 4 can also be transmitted through transfusion and transplantation from an infectious donor. HEV is transmissible through all types of blood components. The infectivity depends on the viral load and the content of plasma in the components. The infectivity of red cell components is 42% (Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 2014;384:1766-73). The highest number of reported cases is associated with the transfusion of RBCs. A meta-analysis of 157 studies on transfusion and exposure risks found that the nucleic acid testing (NAT) and antibody prevalence rates of HEV infection in blood donors were higher in Europe and Asia compared to the United States, Canada, and Australia, where routine screening is not performed. NAT reactivity averaged 0.01% in the U.S., 0.10% in Europe, and 0.14% in Asia. In Japan, following 2.5 years of nationwide screening, NAT reactivity was 0.055%. HEV RNA frequencies ranged from <1:1000 to 1:17,000. The average seroprevalence was 13% in the U.S. and 19% in Europe. (Reference: Wolski A, Pischke S, Ozga A-K, Addo MM, Horvatits T. Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis. Pathogens. 2023; 12(3):425. https://doi.org/10.3390/pathogens12030425).
Time to detection:
Among two retrospective analyses and three case reports, 23 transfusion-transmitted HEV infections were identified. Of these, 14 cases were linked to red blood cell transfusions, with three cases occurring in each report and 11 identified in the retrospective study. The time from the transfusion to the onset of symptoms varied within a broad interval of approximately 1 to 3 months. In the retrospective study from Japan, the viral concentration of components responsible for transfusion-transmitted HEV varied from 1.53 × 10² to 5.33 × 10⁶ IU/mL. For other reported cases, the estimated viral load ranged from 17,000 to 316,227 IU/mL.
Alerting signals, symptoms, evidence of occurrence:
All transfusion recipients who developed transfusion-transmitted HEV had weakened immune systems due to immunosuppression from drugs or systemic diseases. The alerting signal was acute hepatitis, manifesting as jaundice, elevated alanine aminotransferases, and cholestasis. In two cases, the patients were receiving potentially hepatotoxic medications, and the discontinuation of these did not improve the symptoms. Immunosuppression likely causes the moderate illness of transfusion-transmitted HEV, but it may lead to the establishment of chronic sequelae (2 cases in Japan). The evidence of occurrence was the detection of both HEV RNA and IgG/IgM anti-HEV antibodies in the patient and the donor. HEV RNA genotype 3 was predominantly identified, alongside genotype 4 (in Japan).
Demonstration of imputability or root cause:
The evidence of transfusion-transmitted HEV was the same HEV strain of genotype 3 in the transfused RBC products and the patient’s serum. Patients showed no evidence of alimentary exposure, and the involved donors were asymptomatic during the index donation while exhibiting alimentary exposure to HEV.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Suggest new keywords:
HEV, red blood cells, transfusion
Reference attachment:
Suggest references:
1) Riveiro-Barciela M. Red blood cell transfusion-transmitted acute hepatitis E in an immunocompetent subject in Europe: a case report.
2) Haim-Boukobza S. Transfusion-transmitted hepatitis E in a misleading context of autoimmunity and drug-induced toxicity.
3) Satake M, et al. Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression. Transfusion. 2017 Feb;57(2):280-288.
4) Ojea AM, et al. Transfusion-transmission of hepatitis E virus through red blood cell transfusion but not through platelet concentrates: A case report from Spain. Transfusion. 2023 Sep;63(9):1767-1772.
5) Ticehurst JR, et al. Probable transmission of hepatitis E virus (HEV) via transfusion in the United States. Transfusion. 2019 Mar;59(3):1024-1034.
Expert comments for publication:
In the case detected through retrospective analysis in the US, the HEV RNA (genotype 3) positive donation was linked to the recipient of RBCs, demonstrating an eightfold increase in IgG anti-HEV. The HEV RNA was not detected in the patient’s sample, and his clinical data remained unavailable. This is the first report of probable HEV transmission via transfusion in the US.