Hepatitis E Virus in Transfusion and Transplantation

1. Hepatitis E Virus in Transfusion and Transplantation Lorna Williamson NHS Blood and Transplant, England.

2. HEV in UK • Number of reported infections in population increasing • 1 in 2850 blood donors positive in study in 2011-12 • First UK transmission 2006; then three cases 2011-14 • Literature: • Case series of chronic carriage/progression to chronic liver disease in immunosuppressed • Worsening of pre-existing liver disease • Other clinical features as well as hepatitis • One transmission via transplanted liver UK situation & state of knowledge both rapidly evolving

3. HEV natural history • Hyper-endemic in developing world (water), genotypes 1 and 2 • Increasing in W Europe, genotypes 3 and 4; linked to pork, wild boar, venison • Incubation period 40 days; virus in blood for 3 weeks; then IgM and IgG with viral clearance; virus in stool for 2 more weeks • Asymptomatic or mild symptoms; jaundice rare: ? BUT fulminant/chronic if immunosuppressed • Susceptibility to re-infection unclear

4. Prevention and treatment • Thorough cooking of pork products • Hand hygiene in food handlers • No vaccine licenced in Europe • Most cases need no specific treatment • In immunosuppressed, ribavirin for 3 months effective; ?interferon

5. HEV infection in UK • Evolving • Clinical cases increasing (PHE enhanced surveillance/new phylotype): • England: 600/yr in 2012 to 800/yr in 2014 • Scotland 13/yr in 2011 to 160/yr in 2014 • N Ireland 3 cases in 10 years to 9/yr in 2014 • Attack rate: 0.1-0.2%/yr = 1 in 500/yr. • Prevalence of immune antibody: • 13% England/4% Scotland (?now higher) • Increases with age • May have fallen over last 20 years

6. HEV reported infections in England 2002-2013

7. Viraemia rates from blood donor studies

8. UK transfusion transmissions

9. Risks in specific transfusion recipients No clinical cases reported via transfusion: • Pregnancy • Neonates & infants • Haemoglobinopathy patients • HIV positive people (though HEV is described) BUT low awareness of HEV amongst clinicians

10. NHSBT/PHE donor/recipient study(Hewitt et al Lancet 2014) • Only donor/recipient study so far • Donors 1 in 2848 virus positive • 18/43 recipients had evidence of HEV (40%)- 6 had antibody and 12 RNA • Transmission from red cells, FFP, platelets, granulocytes • Transmission rates higher if high viral load/large plasma volumes (small nos)

11. HEV in immunosuppressed • Small case series reporting progression to chronic carriage/liver disease in up to 60% of infected solid organ transplants • Chronic liver disease also reported in stem cell transplant recipients (case reports) • Chronic carriage in some HIV positive people • May make chronic liver disease acute

12. Effect of immune suppressionon recipient outcome(Hewitt et al Lancet 2014)

13. Clinical features other than hepatitis • Mainly studied by Dalton et al in Exeter; SW England • Neurological: Guillain-Barré, neuropathies • Renal, pancreas, thyroid • Low platelets, high lymphocytes • Remain to be confirmed in other series

14. Strategies to provide ‘HEV-safe’ blood components

15. RNA HEV testing of blood donors • 2 CE marked suppliers • Can be done in 16-24 pools • Confirmatory assay available • Would generate 3-4 positive donors/day • Manageable impact on supply • Donors would be informed, deferred & retested before return to donation • Lookback if previous recent donations ? < 4 months

16. International situation re blood donor screening • Netherlands- decision not to test (1 in 500 pos) • France: testing for Octaplas manufacture; otherwise being discussed • Ireland: request for funding to test entire blood supply for 5 years • Other EU countries: reviewing data • Not an issue for N America, Australia, Japan

17. Pathogen inactivation • No licensed systems for red cells • Platelets • Mirasol- no information, little routine use • Intercept- no information, no transmissions • FFP • Intercept - 2 transmissions • Methylene blue - no information • Solvent detergent - evolving situation

18. Solvent-detergent FFP • Pooled product, licensed medicinal (Octaplas) • UK guideline: Recommended for plasma exchange for TTP & some inherited clotting disorders • Wales: all patients receive SDFFP (also Ireland) • Scotland: TTP only • England: mixed economy, some use in paeds • Transmissions reported from Canada • Octapharma now requesting tested plasma and will set safe levels for pools • Could become safe option for high risk patients

19. Organ and stem cell transplant recipients appear to be at highest risk of serious clinical sequelae They might acquire HEV from blood, from diet, and from the transplant

20. Transmissions from organs and stem cells • One reported transmission from a liver transplant (not in UK) • One stem cell donor with acute HEV • Approx one organ donor/year calculated to be virus positive

21. Risks to recipients of tissues • No transmissions reported from tissue products • Processing removes most plasma • No immunosuppression needed • Rarely transfused • Hence tissue transplantation low risk

22. Risks to recipients of gametes and embryos • No transmissions reported • Processing of sperm removes plasma • Egg = single cell • Recipients not immunosuppressed • No specific transfusions • Hence seen as low risk procedure

23. Acknowledgements • Pat Hewitt, Richard Tedder, Samreen Ijaz, NHSBT/PHE Bloodborne virus laboratory • Su Brailsford, NHSBT/PHE epidemiology team • James Neuberger, NHSBT organ donation & transplant team