hepatitis e: epidemiology, transmission and treatment · 2012 sausages 93 6 (6.4%) spain di bartolo...
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Hepatitis E:
Epidemiology, transmission and
treatment
Antonio Rivero-Juarez
Unidad de Enfermedades Infecciosas
Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)
Hospital Universitario Reina Sofía
Universidad de Córdoba
Disclosure
• I declare no competing interests for this presentation
• Outside the current presentation, I have received consulting
fees, conference travel support, and lectures fees from:
– Bristol-Myers Squibb
– Abbott
– Roche
– Merck Sharp & Dohme
– Janssen-Cilag
– ViiV Health Care
• I´m not vegetarian
The case of David
• Male, 32 years old
• HIV infected on HAART with undetectable viral
load (CD4+ 357 cells/mL)
• Digestive symptoms: diarrhea and vomit
• Flu-like symptoms
• AST 650 IU/dL and ALT 750 IU/dL
• CMV, Epstein-Barr, HAV, HCV and HVB viral
load: undetectable
• RT-PCR VHE: 100.000 IU/mL
Today´s agenda
• Key virological bullets
• HEV in Europe:
– Epidemiology: an emergence disease?
– Transmission: public health risk?
– Clinical and Treatment: just an acute hepatic disease?
• Conclusions
HEV key virological points
• Orthohepeviridae family1
• RNA+ non-enveloped: 7,2 kba2
• Four know genotypes that can infect humans3
1. Hepeviridae Study Group. J Gen Virol 2014
2. Hoofnagle. NEJM 2012
3. Kamar. Clin Microb Infect 2014
EPIDEMIOLOGY
¿HOW FREQUENT IS HEV?
HEV global distributtion
CDC Public Health Service 2016
HEV in Low income countries:
Country Affected Transsmision Reference
India 29,300 Waterborne Viswanathan et al. J Med Res 1957
Kashmir 270 Waterborne Khuroo et al. Am J Med 1980
Mexico 200 Waterborne Velazquez et al. JAMA 1990
Ethiopia 750 Monsoon rains Tsega et al. J Med Virol 1991
India 79,000 Waterborne Naik et al. WHO 1992
China 119,000 Waterborne Zhang et al. Gastroenterol 1991
Vietnan 300 Waterborne Corwin et al. A J Trop Med Hyg 1996
Sudan 2,600 Waterborne Guthmann et al. Clin Infec Dis 2006
Uganda 10.000 Person-person Teshale et al. Emerg Infec Dis 2010
Bangladesh 62 Waterborne Haque et al. J Viral Hep 2015
Nepal 10.000 Waterborne/ person-person Shrestha et al. Emerg Infect Dis 2015
Adpatated and updated from Teshale EH. Clin Infect Dis 2010
The case of David
• No travel history to high endemic/ epidemic
countries
HEV in high income countries
Ijaz. J Clin Microbiol 2005
Two different diseases
Hoofnagle NEJM 2012
Prevalence of Endemic HEV in Europe
9.3%
20%
4.7%
20%
11%25%
5%
52%
5%
21%
4%4%
4%
5%
15%
HEV prevalence in Córdoba
(HIV patients)
Rivero-Juarez. J Infection 2015
Prevalence: 21.2% (9.8% confirmated by Western-blot)
HEV incidence in Córdoba
(HIV patients)
Incidence rate:
7.2 seroconversion /100 patients-year
Incidence rate:
Rural: 17.4 seroconversion /100 patients-year
Urban: 5.8 seroconversion / 100 patients-years
Rivero-Juarez. CROI 2015
The case of David
• Inhabitant of a rural town of Córdoba
TRANSMISSION
¿HOW COULD BE INFECTED?
Routes of transmission
Direct
Transmission
Blood
HEV viremia in blood donors
Country Tested Positive Reference
Austria 58,915 7 (0.01%) Fischer et al. PLoS One 2015
England 225,000 79 (0.03%) Hewit et al. Lancet 2014
USA 18,829 9 (0.04%) Stramer et al. Transfusion 2015
France 89 (HSC) 0 (0%) Frange et al. J Infection 2015
The case of David
• No blood transfusion
Routes of transmission
Direct
Transmission
Blood
HEV in animals
Siridhar S. J Formo Med Ass 2015
HEV seroprevalence in pigs
12.5%
39%
63%
61%
65%
30%
27%
75%
92.8%
50%
HepEpork Study: Pigs
• Córdoba: 2nd province of Spain in Pork production
• Home-town of Black Iberian pig
Intensive
farming
Extensive farming
HepEpork Study (partial data)
Global
0
20
40
60
80
100
% o
f p
igs
HE
V-R
NA
po
sitiv
e
N = 499
22.2%
• 13 farms tested (26 farms proyected)
• 499 pigs tested (1040 pigs proyected)
Intensive farming Extensive farming
0
20
40
60
80
100
Farm
% o
f p
igs
HE
V-R
NA
po
sit
ive
N = 419 N = 80
15.5%
57.5%
p < 0.001
Rivero-Juarez. [Unpublished data]
• 40 animals per farm tested
• Prevalence: 8/13 (61.5%)
The case of David
• Not veterinarian
• No relation with pigs farming
HEV viremia in wild life
3.3%
16%4%
20%
19%
11%
HepEpork Study: Wild boar
• Wild boars: in contact with extensive farming
Rivero-Juarez. [Unpublished data]
HepEpork Study: Wild boar
• 45 wild boars tested
Global
0
20
40
60
80
100
% o
f w
ild
s b
oa
r H
EV
-RN
A p
os
itiv
e
N = 45
55.5%
Rivero-Juarez. [Unpublished data]
The case of David
• Father and brother: wild boar hunters
Routes of transmission
Direct
Transmission
Blood
Presence of HEV in food (pork)Pork related food Tested HEV-RNA Country Reference
Raw liver sausages 45 10
(22%)
Italy Di Bartolo et al. Inter J Food Microb 2015
Meat 40 1
(2.5%)
Czech Republic Di Bartolo et al. Inter Emerg Infec Dis
2012
Sausages 93 6
(6.4%)
Spain Di Bartolo et al. Inter Emerg Infec Dis
2012
Meat 33 2
(6%)
Italy Di Bartolo et al. Inter Emerg Infec Dis
2012
Foie related 394 68
(17.2%)
France Pavio et al. N Emerg Infect Dis 2015
Chops 878 31
(3.5%)
Canada Wilhekm et al. Inter J Food Microbiol
2014
Sausages 63 6
(9.5%)
UK Berto et al. Emerg Infect Dis 2012
Presence of HEV in other foodMollusk Tested HEV-RNA Country Reference
Mussel 37 3
(8.1%)
Italy Donia et al. J Viro Meth 2012
Mussel 51 0
(2.5%)
Finland Diez-Valcarce et al. Food Environ Virol
2012
Mussel 51 3
(6%)
Spain Diez-Valcarce et al. Food Environ Virol
2012
Clams 65 5
(7.6%)
France Grodzki et al. AEM 2014
Cockles 49 6
(12.5%)
France Grodzki et al. AEM 2014
Mussels 94 7
(7.4%)
France Grodzki et al. AEM 2014
Oyster 66 3
(4.5%)
France Grodzki et al. AEM 2014
The case of David
• Consumption of undercooked wild boar
The case of David
Father Mother
Brother Sister Sister DavidBrother
in law
Rivero-Juarez. [Unpublished data]
The case of David
Brother
(40.000 UI/mL)
Sister
(30.000 UI/mL)
Sister
(30.000 UI/mL)
David
(20.000 UI/mL)
Father
(50.000 IU/mL)Mother
(20.000 IU/mL)
Brother in law
(30.000 UI/mL)
Rivero-Juarez. [Unpublished data]
The case of David
200.000 UI/mL 150.00 UI/mL
Phylogenetic analysis in process
Rivero-Juarez. [Unpublished data]
Routes of transmission
Direct
Transmission
Blood
Veggies? Breast feeding?
Others
The case of David
Brother
(40.000 UI/mL)
Sister
(30.000 UI/mL)
Sister
(30.000 UI/mL)
David
(20.000 UI/mL)
Father
(50.000 IU/mL)Mother
(20.000 IU/mL)
Brother in law
(30.000 UI/mL)
4 months8 years
Breast feeding?Rivero-Juarez. [Unpublished data]
The case of David
1.000 IU/mL
Children currently under studyRivero-Juarez. [Unpublished data]
CLINICAL AND TREATMENT
¿Is just an hepatic disease?
Clinical manifestation:
Woolson Aliment Pharmacol Ther 2014
Extra-hepatic manifestations
Aggarwal. Virus reserach 2011 Woolson Aliment Pharmacol Ther 2014
Special population:
Cirrhotic patientsHigher mortality Higher decompensation rate
Rivero-Juarez. CROI 2015Acharya. J Hepatol 2007
Special population:
HIV infected patients
Rivero-Juarez. CROI 2015
Special population:
HIV infected patients
Rivero-Juarez. J Infection 2015Dalton. NEJM 2009
The case of David
0
20000
40000
60000
80000
100000
120000
0 7 14 28 35 42
HEV-RNA (IU/mL)
HEV-RNA (IU/mL)
HE
V v
ira
l lo
ad
(IU
/mL)
Days since diagnosticRivero-Juarez. [Unpublished data]
Treatment
Peters van Ton J Viral Hep 2015
Conslusions
• HEV is frequent in EU
• The prevalence found in pigs and wild animals is
high
• The presence of the virus in food is frequent,
supposing an important route of transmission
• The course: mainly acute self-resolved
• Treatment not well established: RBV 6 months?
• Preventive measures in high risk population:
Farm testing?
Acknowledgement
InstitutionsHospital Universitario Reina Sofía:
• UGC Enfermedades Infecciosas
• UGC Análisis Clínico Hospital
Enfermedades Infecciosas Hospital Valme
HepEpork Study Team:• Mario Frias
• Isamel Zafra
• Diego Rodriguez Cano
• Laura Ruiz
• Angela Camacho
• Francisca Cuenca
• Ana Gordon
• Antonio Martinez
• Angeles Risalde
• Jose Carlos Villamandos
• Vicente Fernandez