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

Hepatitis E Virus in
Transfusion and Transplantation
Lorna Williamson
NHS Blood and Transplant,
England.
HEV in UK
1.
2.
3.
4.
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
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
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
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
HEV reported infections in
England 2002-2013
Viraemia rates from
blood donor studies
Country
Year
RNA positive
France
2012-13
1in 2218
Netherlands
2013
1 in 1761
Netherlands
2011-12
1 in 2671
Germany
2011
1 in 1240
Scotland
2004-08
1 in 14,520
England
2012-13
1 in 2848
UK transfusion transmissions
# 1:
2006
#2:
2011
#4:
2014
Lymphoma Stem cell
Discovered transplant
via
recipient
lookback
#3:
2012
Ca. bladder
Ca. prostate
(129 donor
exposures)
Red cells
FFP
FFP
FFP
Cleared
virus
Died other
causes
Cleared
virus
Cleared
virus
Liver
disease
Encephalo
pathy
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
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)
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
Effect of immune suppression
on recipient outcome
(Hewitt et al Lancet 2014)
NONE/MILD
MODERATE
SEVERE
n= 8
n=6
n=4
10 weeks of
infection
Anti-HEV in 8
18 weeks of
infection
Anti-HEV in 5
30 weeks of
infection
Anti-HEV in 2/3
Viral clearance
in 8
Clinical
hepatitis: 1
Viral clearance
in 3/4
Clinical
hepatitis: 0
Viral clearance
in 2/3
Clinical
hepatitis: 0
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
Strategies to provide ‘HEV-safe’
blood components
Donor selection by
occupation or diet
No
(vegetarians only 7%)
Test donors for HEV
RNA
Yes
Create donor panel with No
immune anti-HEV
Pathogen inactivation of Uncertain
FFP or platelets
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
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
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
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
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
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
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
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
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