Hepatitis E screening for blood donations: an urgent need?
Authors: Jean-Michel Pawlotsky
Journal: The Lancet (2014)

In The Lancet, Patricia Hewitt and colleagues1Hewitt EP Ijaz S Brailsford SR et al.Hepatitis E virus in blood components: a prevalence and transmission study in southeast England.Lancet. 2014; (published online July 28.)http://dx.doi.org/10.1016/S0140-6736(14)61034-5PubMed Google Scholar report the prevalence of hepatitis E virus (HEV) RNA in 225 000 blood donations from southeast England. Their study was based on HEV RNA detection by means of reverse transcriptase real-time PCR in minipools of 24 donations or fewer collected in a 1-year period (2012–13). They defined the rate of transmission from HEV-containing blood components, investigated the factors associated with transmission, and looked at the outcomes of recipients of HEV-containing blood components. HEV RNA was noted in roughly one in every 2848 (0·04%) blood donations tested. When projected across England, this prevalence suggests that about 80 000–100 000 acute HEV infections are likely to have occurred countrywide during the year of the study. Overall, 79 HEV genotype 3 RNA-positive donations, 56 of which (71%) were seronegative, were used to prepare 129 blood components; 62 were transfused, resulting in 18 documented infections (42%) among the 43 recipients who could be followed up. The components associated with transmission included platelet preparations, red cells, granulocyte pools, and fresh frozen plasma. The median times for seroconversion and duration of infection depended on the degree of immunosuppression. Ribavirin treatment was started in one severely immunosuppressed infected recipient, and the level of immunosuppression was reduced in one moderately immunosuppressed patient and one severely immunosuppressed patient, to induce viral clearance. Among the other patients, four died, one remained viraemic, and the remaining infections cleared spontaneously. These results are interesting and can inform the ongoing debate about HEV and blood safety. The HEV genome was cloned in 1990 and this virus was identified as the main causative agent of enterally transmitted non-A, non-B hepatitis. Four genotypes, 1 to 4, have subsequently been identified in human beings. HEV was initially thought to be present mainly in low-income or middle-income areas, where poor hygiene conditions favour faecal–oral transmission of genotypes 1 and 2, resulting in frequent sporadic cases and large outbreaks of acute hepatitis related to the contamination of drinking water. More recently, HEV genotypes 3 and 4 were reported as zoonotic infections in the developed world, causing acute hepatitis cases in occupationally exposed individuals or consumers of infected meat that had been insufficiently cooked.2Kamar N Dalton HR Abravanel F Izopet J Hepatitis E virus infection.Clin Microbiol Rev. 2014; 27: 116-138Crossref PubMed Scopus (428) Google Scholar Acute hepatitis E is generally mild and self-limiting. However, HEV infection is not always harmless. Severe cases, including subfulminant or fulminant hepatitis, have been reported in patients with underlying chronic liver disease.3Peron JM Bureau C Poirson H et al.Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathy.J Viral Hepat. 2007; 14: 298-303Crossref PubMed Scopus (220) Google Scholar HEV infection can induce various types of eventually severe extrahepatic manifestations, such as neurological symptoms, kidney injury, pancreatitis, or thrombocytopenia, and aplastic anaemia;2Kamar N Dalton HR Abravanel F Izopet J Hepatitis E virus infection.Clin Microbiol Rev. 2014; 27: 116-138Crossref PubMed Scopus (428) Google Scholar a higher mortality owing to HEV infection has been reported in pregnant women than in the general population during large outbreaks in low-income areas, the causes of which remain debated.2Kamar N Dalton HR Abravanel F Izopet J Hepatitis E virus infection.Clin Microbiol Rev. 2014; 27: 116-138Crossref PubMed Scopus (428) Google Scholar Chronic HEV infection has been reported in immunocompromised patients, including recipients of solid organ transplants and haemopoietic stem cell transplants, patients receiving chemotherapy, HIV-infected individuals, and patients taking steroids.4Dalton HR Bendall RP Keane FE Tedder RS Ijaz S Persistent carriage of hepatitis E virus in patients with HIV infection.N Engl J Med. 2009; 361: 1025-1027Crossref PubMed Scopus (419) Google Scholar, 5Kamar N Selves J Mansuy JM et al.Hepatitis E virus and chronic hepatitis in organ-transplant recipients.N Engl J Med. 2008; 358: 811-817Crossref PubMed Scopus (1024) Google Scholar, 6Ollier L Tieulie N Sanderson F et al.Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab.Ann Intern Med. 2009; 150: 430-431Crossref PubMed Scopus (171) Google Scholar Chronic HEV infection can cause chronic liver disease that rapidly evolves towards cirrhosis in roughly 10% of cases, with a risk of lethal liver failure.7Kamar N Garrouste C Haagsma EB et al.Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants.Gastroenterology. 2011; 140: 1481-1489Summary Full Text Full Text PDF PubMed Scopus (467) Google Scholar Blood transfusion is known to be a route of HEV transmission in immunocompromised patients.8Coilly A Haim-Boukobza S Roche B et al.Posttransplantation hepatitis E: transfusion-transmitted hepatitis rising from the ashes.Transplantation. 2013; 96: e4-e6Crossref PubMed Scopus (33) Google Scholar, 9Khuroo MS Kamili S Yattoo GN Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area.J Gastroenterol Hepatol. 2004; 19: 778-784Crossref PubMed Scopus (165) Google Scholar We recently reported in The Lancet that 5 of 367 consecutive liver transplant recipients (1·4%) acquired chronic hepatitis E through blood transfusion and subsequently developed persistent liver graft damage.10Feray C Pawlotsky JM Roque-Afonso AM Samuel D Dhumeaux D Should we screen blood products for hepatitis E virus RNA?.Lancet. 2014; 383: 218Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar The prevalence of HEV RNA in blood donations in England reported by Hewitt and colleagues is in keeping with findings from studies in other European countries (one in 1240 donations in Germany11Vollmer T Diekmann J Johne R Eberhardt M Knabbe C Dreier J Novel approach for detection of hepatitis E virus infection in German blood donors.J Clin Microbiol. 2012; 50: 2708-2713Crossref PubMed Scopus (125) Google Scholar and one in 1761 donations in the Netherlands12Hogema BM Molier M Slot E Zaaijer HL Past and present of hepatitis E in the Netherlands.Transfusion. 2014; (published online May 29.)https://doi.org/10.1111/trf.12733Crossref Scopus (69) Google Scholar). Despite this high prevalence, the high rate of transmission by infected blood or blood products, the non-negligible morbidity and mortality related to HEV infection (especially in patient populations exposed to blood or blood product transfusion), and the lack of efficient antiviral therapy, Hewitt and colleagues surprisingly conclude that "there seems no pressing need to move rapidly with the introduction of donation screening". Although cost-effectiveness studies have not been done and might not show a substantial economic benefit of blood donation screening for HEV, the history of viral infections in blood transfusion should help stakeholders to make quick decisions. The public scandals related to the delay in implementation of HIV antibody screening in blood donations in several countries in the 1980s taught us that societies in high-income countries are extremely sensitive to the safety of medical procedures, especially those related to the use of blood and blood products. The medical threat of hepatitis E is obviously not comparable to that of HIV. However, it is useful to remember the conditions that led to the implementation of nucleic acid testing of blood donations for other transfusion-transmitted viral infections 15 years ago. Because the transmission of HIV and hepatitis C virus (HCV) had been substantially reduced by the use of serological testing for p24 antigen and specific antibodies, the implementation of nucleic acid testing in blood banks was not estimated to be cost effective and was not recommended by most scientific experts. Despite this view and because of the context, the decision was made by the political authorities and blood services to implement pooled nucleic acid testing in Europe and the USA. In the USA, in the first year only 62 HCV RNA-positive, antibody-negative donations were identified among more than 16·3 million donations screened (1:263 000), whereas only 4 HIV RNA-positive, p24 antigen-negative donations were found among more than 12·6 million donations screened (1:3 150 000).13Stramer SL Nucleic acid testing for transfusion-transmissible agents.Curr Opin Hematol. 2000; 7: 387-391Crossref PubMed Scopus (18) Google Scholar Numbers of the same order of magnitude have been reported in western Europe.14Coste J Reesink HW Engelfriet CP et al.Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003.Vox Sang. 2005; 88: 289-303Crossref PubMed Scopus (101) Google Scholar Despite this modest impact, nucleic acid testing of blood donations is still obligatory or recommended for HIV, HCV, and hepatitis B virus. The risk of transmission for HEV at present is far higher than for viruses such as HIV, and should be interpreted in the context of the poor sensitivity and specificity of anti-HEV antibody testing for infectivity in the blood bank setting. The potential clinical results of blood-borne HEV infection should not be downplayed; in particular, the risk of serious complications and death exists. Thus, on the basis of Hewitt and colleagues' and other studies, I believe that systematic screening of blood components for markers of hepatitis E infection should be implemented in areas where HEV is endemic (eg, the European Union), based on HEV RNA detection. No doubt this position will be debated and, whatever the experts think, a political decision will have to be made. I suspect that pooled HEV RNA testing will become obligatory in blood banks soon. I declare no competing interests. Hepatitis E virus in blood components: a prevalence and transmission study in southeast EnglandOur findings suggest that HEV genotype 3 infections are widespread in the English population and in blood donors. Transfusion-transmitted infections rarely caused acute morbidity, but in some immunosuppressed patients became persistent. Although at present blood donations are not screened, an agreed policy is needed for the identification of patients with persistent HEV infection, irrespective of origin, so that they can be offered antiviral therapy. Full-Text PDF Open Access