Original Research
Transfusion-Transmitted Hepatitis E Virus Infection in France

https://doi.org/10.1016/j.tmrv.2019.06.001Get rights and content

Highlights

  • Hepatitis E virus (HEV) has emerged in France as well as elsewhere in Europe as a significant transfusion risk.

  • Such transfusion-transmitted (TT) HEV infections occur with red cells, platelets and fresh-frozen plasma.

  • Current pathogen inactivation technologies for blood products are unable to prevent TT HEV infection.

  • Transfusion-transmitted HEV infection can result in chronic severe hepatitis in immunosuppressed patient.

  • Where HEV is endemic, enhanced clinical awareness as well as blood donation screening will mitigate the risk associated with TT HEV infection.

Abstract

There is growing concern regarding the risk of transfusion- transmitted (TT) hepatitis E. Since the first described case in 2006, several TT hepatitis E have been reported to the French hemovigilance network. We performed a retrospective analysis of all cases of TT hepatitis E reported between 2006 and 2016. Transfusion-transmitted hepatitis E with high imputability according to phylogenetic analysis occurred in 23 patients aged 8 to 88 years and involved mostly solid organ recipients (n = 9) or patients with malignant hematological diseases (n = 9, including 4 hematopoietic allograft recipients). Involved blood products were plasma (n = 7), among which 6 had undergone pathogen reduction with solvent/detergent (n = 4) or amotosalen + ultra-violet A (UVA) (n = 2 from 1 donation) treatments, red blood concentrates (n = 7), apheresis platelets concentrates (n = 3) and whole blood pooled platelets concentrates (n = 6), among which one had underwent amotosalen + UVA treatment. Median hepatitis E virus (HEV) RNA dose infused was 5.79 [4.36–10.10] log IU. HEV infection progressed to chronic hepatitis E in 14 (61%) immunocompromised patients, 2 of whom had advanced liver fibrosis at diagnosis. Chronic hepatitis E patients cleared HEV with ribavirin treatment (n = 10), after immunosuppressive drug reduction (n = 3), or spontaneously (n = 1). One additional organ transplant recipient with associated co-morbidities died with ongoing HEV infection and multiple organ failure. The other 8 (34.8%) patients with TT hepatitis E cleared HEV within 6 months with ribavirin treatment (n = 3), reduced immunosuppression (n = 1) or spontaneously (n = 4). Red cells, platelets, and plasma transfusions may be associated with TT hepatitis E that can evolve to chronic hepatitis E in immunocompromised patients. Hepatitis E virus has emerged in France as a clinically significant TT infection risk.

Section snippets

Blood Products in France

In France, collection, qualification, preparation and distribution of labile blood products for civilians are under the exclusive responsibility of a national transfusion public service: Etablissement Français du Sang (EFS).

During the study period (2006—2016), approximately three million labile blood products were transfused annually in France including 2.4 million of red blood cells concentrates (RBC), ~300 000 platelets concentrates including~ 50 to 60% whole blood-derived pooled platelets

Patients

In 2006, the first case of TT HEV was reported in France in a 8 year-old child treated for a kidney tumor (#1, Table 1) [15]. Up to December 2016, 78 suspected cases of possible HEV-TT were reported to the French hemovigilance network.

In 22 of these 78 cases, TT HEV was excluded based on negative HEV NAT of all blood products transfused to the patients. Imputability was deemed non-evaluable in 4 cases. In 29 cases, absence of evaluable recipient viral genome or inconclusive phylogenetic

Discussion

With 23 reported cases of transfusion-transmitted infections of high imputability between 2006 and 2016 in France, including 14 with chronic hepatitis, HEV has emerged as a significant infectious transfusion risk. These cases highlight the clinical burden associated with TT-HEV, while most probably only representing a fraction of the current occurrences. Indeed, and despite recent progress, hepatitis E may be misdiagnosed. HEV infection is often asymptomatic in immunocompetent patients. Chronic

Author's contributions

PG, RD and PT designed the study; all authors contributed data; PG, EP, RD and PT wrote the first draft; JI, AMRA, NK and VM further contributed to the writing of the manuscript; all authors reviewed and approved the final version of the manuscript.

Conflict of Interest

PG, EP, RD, SG, PB, AA and PT are employed by the French transfusion public service (Etablissement Français du Sang) in charge of blood products manufacturing and issuing in France.

Acknowledgments

The authors express their thanks to the French hemovigilance network members for the careful reporting of these cases.

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    1

    Contributed equally.

    2

    Current affiliation: Direction Générale de la Santé, Ministère de la Santé, Paris, France.

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