Hepatitis E virus in France

1. Hepatitis E virus infection,
France, 2002-2015
Elisabeth Couturier
Institut de Veille Sanitaire
ECDC December 2015

2. Objectives
To describe main hepatitis E virus infection
surveillance data in France, 2002-2015

3. Data sources
Surveillance systems
• National Reference Centre (NRC), 2002-2014
• Other sources
 Hospital discharge reports (2004-2014)
 Reimbursement data of anti-HEV EIA tests (2005-2014)
Investigations and studies
• Outbreak investigations (2005-2015)
• National descriptive study of autochthonous cases (2010)
• Case control study (2015)
• Seroprevalence studies (2003-2012)

4. National Reference Centre (NRC),
2002-2014
• Diagnostic algorithm
 Immunocompetent
IgM(+) = recent infection to confirm by PCR
IgM(-) = no recent infection
 Immunocompromised
* IgM(+) and HEV RNA(+) = recent or active infection
Clearance or persistence by testing for HEV RNA
* IgM(-) and HEV RNA(-) = no recent infection

5. Number of tested persons,
imported and autochthonous hepatitis E cases,
2002-2014, France (source: NRC)
1
10
100
1000
10000
100000
2002 2004 2006 2008 2010 2012 2014
N tested
N autochthonous
N imported

6. Number of tested persons,
imported and autochthonous hepatitis E cases,
2002-2014, France (source: NRC)
Year Tested persons
(N)
Cases (n) HEV(+) (n/N)
(%)
Imported Autochthonous Total
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
209
155
233
327
583
1 012
1 700
2 150
2 549
3 429
17 566
35 416
44 382
4
11
4
19
14
10
21
23
16
19
9
3
12
9
3
16
20
24
97
159
183
216
249
801
1 848
1 813
13
14
20
39
38
107
180
206
232
266
801
1 851
1 825
6
9
8
12
6
10
10
10
9
8
5
5
4

7. HEV genotypes, France, 2007-2014 (source: NRC)
0
50
100
150
200
250
300
350
400
450
500
2007 2008 2009 2010 2011 2012 2013 2014
HEV 1
HEV 2
HEV 3
HEV 4

8. HEV 3 subtypes, France, 2007-2014 (source: NRC)
0
50
100
150
200
250
300
2007 2008 2009 2010 2011 2012 2013 2014
3a
3b
3c
3e
3f
3i
3c
3e
3f

9. Characteristics of autochthonous hepatitis E cases,
2002-2014, France (source: NRC)
Year M/F sex ratio Mean age (y) Southern
regions*
2002-2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
3
1,8
2,7
2,7
4,6
2,9
2,6
2,5
ND
1,9
45
45,5
56
56
61
55
55
55
ND
55±15
70%
65%
72%
60%
57%
50%
ND
40%
ND
45%
*Aquitaine, Corse, Midi-Pyrénées, Languedoc-Roussillon, Provence-Alpes-Côte d’Azur

10. Number
 Case definition : ICD-10 code B17.2 (acute hepatitis E)
 M/F sex ratio = 2.2; mean age = 54.5y
 Hospitalisation incidence rate
regional disparity  0.2-1.2/100,000
 highest in southern regions
Hospital discharge reports (2004-2014)
0
100
200
300
400
500
600
700
800
2004 2006 2008 2010 2012 2014
Hospital
stay
Case
Year
Year

11. Number
Reimbursement data of anti-HEV EIA tests,
2005-2007 and 2010-2014
0
5000
10000
15000
20000
25000
30000
2005 2006 2007 2010 2011 2012 2013 2014
HEV EIA

12. Outbreak investigations (2005-2015)
Year Population Indigenous
cases (N)
Suspected source
2005-2006
2007
2007-2009
2009
2011
2011
2012
2013
2013
2015
ND*
4
18
4
59
ND*
200
15
111
200
6
3
7
1
7
11
4
2
17
7
environment
raw figatelli**
raw figatelli**
raw figatelli**
unknown
raw figatelli**
unknown
raw smoked ham
undercooked pig liver
stuffing
private well connected to
public water supply
*not documented; **pork liver sausage

13. • National descriptive study of autochthonous cases (2010)
 N = 139; sex ratio M/F = 2.9; median age 55 y [18-86]
 65% residing southern France
 60% jaundice; 6% reported neuralgic amyotrophy at symptom onset
 19% immunocompromised
 74% subtype 3f
 39% consumed raw pig-liver based products
 More frequent in SE regions (52%) compared to SW (33%) and North (25%)
 raw pork-liver products may be a risk factor
• Case control study (2015): ongoing
 To estimate the fraction of cases attributable to consumption of raw pig-liver
products, other risk factors
 Frequency and characteristics of neurologic disorders
Studies

14. HEV seroprevalence studies, 2003-2012, France
Year Regions Population Seroprevalence
2003-2004
2010
2009-2010
2011
2011-2012
2011
2012
1 (SW)
France
5 (East)
6
2 (South)
France
blood donors (n=529)
same blood samples
general (n=5,400)
forestry workers (n=593)
pig farm workers (n=306)
tertiary employees (n=322)
forestry workers (n=231)
blood donors (n=3,353)
blood donors (n=861)
16.6%
52%* [48-57]
4.9% [4.1-5.8]
31%
44%
26%
36%
39.1%* (IgG)
3.3%* (IgM)
23.6%* (IgG)
*Wantai HEV IgG assay

15. • 1rst published French case of transfusion-associated hepatitis E
(Colson et al, Emerg Infect Dis 2007)
• November 2012-December 2013
 53,234 blood donations
 0.045% [0.043-0.047]
estimated detection rate of HEV RNA in plasma donation
 1 HEV(+) sample/2,218 blood donations
 2-fold greater in southern France
 adjusted on region, age and sex 1/3,800 [1/6,200-1/2,700]
• 2013-2014 : systematic testing for HEV RNA
on plasma processed with solvent-detergent
• Since 2015: testing for HEV RNA
to have in stock 20-30% of plasma VHE free
Blood transmission

16. • Various sources: NRC, private laboratories, hospital, descriptive study
• HEV cases: male, mid-fifties, southern France
• Since 2002-2004, increasing trends (autochthonous cases, hospitalisation)
due to increasing awareness and tests availability
• Molecular surveillance
• Higher prevalence in southern France
• Small outbreaks
• Foodborne transmission: consumption of raw pork-liver products
• Labelling “Cook thoroughly” on raw pig-liver products (2009)
• Case control study: other risk factors?
Conclusion