1) Screening of over 500,000 Dutch blood donations from 2017-2018 found 231 positive for HEV, a rate of about 1 in 2,447 donations. Genotyping showed all were genotype 3. 2) Previous screening of plasma donations from 2012 found a record high prevalence of about 1 in 600 people being viremic on a given day, equivalent to an annual incidence of 1%. 3) A case study describes a chronically immunocompromised patient who developed chronic hepatitis E in 2014 despite multiple treatment attempts, demonstrating the clinical impact for vulnerable patient groups.

1. HEV in Holland
part 1:
HEV in Dutch blood donors
ECDC, Stockholm, Nov. 28-29th, 2018.
prof.dr. Hans L. Zaaijer, MD PhD, medical microbiologist
Sanquin Blood Supply Foundation &
Amsterdam University Medical Centers

2. - HEV PCR on pools of 24 donations.
- July 3rd 2017 – Nov 4th 2018: 565.207 donations , avg. 8074 / week.
- 231 / 565.207 confirmed HEV+ , 1 : 2447 donations.
Yield of HEV PCR donorscreening in NL,
as started on July 3rd 2017.

3. Yield of screening of NL plasmadonations,
in pools of 96, as of Oct. 2012
- HEV PCR screening of 2000 - 3000 plasmadonations / month, in pools of 96.
- Record high medio 2014:
approx. 1:600 persons viremic on any given day (= incidence of 1% / year).
(previous slide)

4. Distribution of HEV viral loads
in 231 PCR positive blood donors.
(July 3rd 2017 – Nov 4th 2018)

5. Serology of 231 PCR+ donations: HEV IgG in 116 follow-up (later) donations:
161 (70%) IgM neg IgG neg ► 116/116 IgG pos = seroconversion
9 (4%) IgM pos IgG neg HEV IgG in 59 previous donations:
47 (20%) IgM pos IgG pos
◄
58 IgG neg → seroconversion in index
14 (6%) IgM neg IgG pos 1 IgG weak pos.
▼
PCR on 83 previous (≤3 months) donations: 58/59 seroconversions imply:
HEV IgG testing is specific,
"27% overall seroprevalence" is reliable.78 (94%) repository: PCR neg.
5 (6%) repository: PCR pos.
HEV genotyping of 75 donations:
75 (100%) HEV genotype 3
Additional testing of the 231 HEV PCR+ donors
serology, follow-up, genotype
© H.L.Zaaijer, Sanquin 2018

6. • Genotyping performed
on 35 donations (2016-
2017) with high load:
33/35 genotype 3c
• HEV sequences cluster
with sequences found in
Dutch liver sausages and
paté (anno 2017)
• NB: liver sausages and
paté remain HEV RNA
positive at 80% (2017)
• RIVM + Sanquin:
HEVIG, HEVID studies:
HEV infection associated
with consumption of
‘cervelaat’ and ‘fijnkost’.
HEV genotyping in NL
© Hogema & Zaaijer, Sanquin Research, 2018

7. Estimation of HEV in the Netherlands:
61,000 HEV infections per year; 85 via transfusion (= only 1:700 !).
HEV donor screening (in pools of 24) :
79 HEV transmissions prevented, 6 HEV infections slip through.
1722 Organ- and bone marrow transplant patients per year:
via food: 5.5 chronic cases of hepatitis E / year.
via transfusion: 2.2 chronic cases of hepatitis E / year.
HEV donor screening prevents 79 of 85 transfusion transmissions, and
2.0 of the 2.2 transfusion associated chronic hep E cases annually.
1.4 M€ testing costs/year; ~ € 700,000 per prevented chronic case.
How many HEV infections were prevented?
we applied our previous model, correcting for the lower incidence of HEV:

8. HEV - summary
- HEV PCR donor screening is expensive,
but more cost-effective than ongoing PCR screening
of Dutch donors for HIV, HBV, HCV.
- the real solution: make food safe.
The HEV team at Sanquin:
Boris Hogema, Michel Molier, and Hans L. Zaaijer
© Hans L. Zaaijer, Sanquin, Amsterdam NL 2018

9. part 2:
HEV in NL: clinical impact
(including: failure to cure chronic hep E in a Dutch patient)
ECDC, Stockholm, Nov. 28-29th, 2018.
prof.dr. Hans L. Zaaijer, MD PhD, medical microbiologist
Sanquin Blood Supply Foundation &
Amsterdam University Medical Centers

10. "hepatitis E" = 2 distinct diseases
tropical & travellers hep E
by HEV genotypes 1,2
zoonotic (pig) hep E
by HEV genotype 3
pregnant women 20% fatality no disease
children acute hepatitis no disease
adults acute hepatitis ‘no disease’
middle aged, elderly acute hepatitis acute hepatitis (mild)
extra hepatic: ? - sporadic: neuralgic amyotrophy
- Guilain Barré Syndrome ?
organ- and stem cell
transplant patients*
? chronic hepatitis*, cirrhosis*
* in immuno-suppressed patients HEV IgM and IgG
often remain negative. Please do HEV PCR.

11. adapted from: WHM vd Poel - Current Opinion in Virology 2014, 4:91–96
How do we acquire HEV genotype 3?

12. Clinical impact of hep E in Holland
for example:
Overview of diagnostic HEV PCR testing at Academic Medical Centre (AMC),
Amsterdam, 2011-2018
HEV PCR testing at
AMC Amsterdam
2011 – 2018
HEV PCR
outcome
hospital
of origin
1759 samples submitted
for HEV RNA PCR
248 positive 62 patients:
35 AMC
24 VUmc
1511 negative 3 other

13. Clinical impact of hep E in Holland
Overview of HEV PCR positive patients at
Academic Medical Centre (AMC), Amsterdam, 2011-2018
35 HEV PCR+ patients
in AMC hospital,
Amsterdam, 2011 – 2018
gender
duration of
documented
PCR+ episode
course of
hep E
outcome
28
12 at nefrology
21 male 14 ≤ 6 mo
10 acute 1 no therapy, †
15 at hematology 4 ? 5 resolved spontaneously
7 female 14 > 6 mo1 at reumatology 14 chronic 8 ribavirine: cured
9 riba: cured, but maybe
acute-spontaneously
7
miscellaneous
acute hep E’s,
all resolved
1 feces donor
1 neuralgic amyotrophy
2 ‘ordinary’ acute hep E
1 acute hep E, evolocumab
1 HIV+
1 cardiac patient
2 cured by decrease of
immuno suppression
3 riba: failure
(1 resolved spontaneously later on)
© H.L.Zaaijer, AMC 2018

14. Mr. X
1999: chronic lymphatic leukemia
2006: allogeneic stem cell transplant
2014: recurrence, chemo and chronic hepatitis E
How to save his liver?
© Amsterdam University Medical Center 2018; prof.dr. A.Kater (hematology), dr. M. van der Valk (hepatology), prof.dr. H.L.Zaaijer (clinical virology).

15. Mr. X

16. Mr. X

17. Mr. X (Nov. 2018: we consider
suppressive ribavirine
maintainance therapy)

18. HEV - summary
- endemic, porcine HEV has significant impact
on small, well defined subset of vulnerable patients.
- the real solution: make food safe.
© Hans L. Zaaijer, AMC, Amsterdam NL 2018