hepatitis e - jornadasavancehepatologia.uma.es · new microbes new infect. 2015 15;10:6-12 . eating...
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![Page 1: Hepatitis E - jornadasavancehepatologia.uma.es · New Microbes New Infect. 2015 15;10:6-12 . Eating pork product \⠀猀愀甀猀愀最攀Ⰰ 瀀愀琀攀Ⰰ 攀琀挀尩](https://reader031.vdocuments.co/reader031/viewer/2022013023/5fa908328c2acb47ca7a0a44/html5/thumbnails/1.jpg)
Hepatitis E
María Buti Hospital Universitario Valle Hebron
Barcelona
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Hepatitis E. Casos clínicos
Varón 52 años Dolor hombros y parestesias
tras viaje a la Cerdaña
Varón 49 años Hepatitis aguda en paciente
con púrpura trombótica trombocitopénica
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Caso clínico 1
Varón 52 años
No hábitos tóxicos
Antecedentes: HTA (ramipril, manidipimo) •Sept 2017: dolor hombros bilateral de 48 horas
de duración, con parestesias en EESS
EF: balance muscular y reflejos conservados.
Resto anodino
Antecedente epidemiológico:
Mes previo vacaciones en la Cerdaña
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Caso clínico 1
Analítica: TQ 108%, Bilir 0.92 mg/dL, AST 268 UI/mL [12-50], ALT 470
UI/mL [8-50], FA 135 UI/mL [9-55], GGT 147 UI/mL [55-171], albúmina 3.7
mg/dL [3.5-5]
Rx cervical: normal
Ecografía abdominal: normal
EMG: signos incipientes de neuralgia braquial
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Varón 52 años con hepatitis aguda
Biliar
Infecciones
Hepatitis autoinmune
Drug-induced liver injury
Hepatitis aguda B o C
Hepatitis E
Ecografía normal
No fármacos salvo antihipertensivos
HBsAg, Ig M antiHBc antiVHC, RNA VHC
NEGATIVOS
Electroforesis IgG
Est. AU NEGATIVO
IgM y RNA VHE POSITIVOS
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Hepatitis E Main characteristics:
– Enteric transmission – Epidemic
• Unique viral hepatitis with animal reservoir
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Current magnitude of HEV Annual estimation (2005):
20 million acute infections
3 million symptomatic infections
70,000 deaths per year
?? Chronic infections
Rein DB, et al. Hepatology 2012;55:988–997
Data from GT 1 and 2, therefore it took no account of zoonotic HEV
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Worldwide distribution of HEV
Purcell RH. J Hepatol, 2008
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Hepatitis E. Escenarios
Países subdesarrollados Países desarrollados
August 25, 2016
Genotype 1 and 2 Genotype 3 and 4 Strictly human Human and animals
Link with outbreaks No
Fecal-orally (contaminated water) Zoonosis Blood product transfusion; Transplantation
GT 1- Asia GT 2- Africa and Mexico
GT 3- Europe, Southeast Asia GT 4- France,Italy,Germany, Belgium (pigs), Japan
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HEV in developed countries • Main source of infection: zoonosis • Exceptionally: Transfusion, transplantation • HEV RNA have isolated in many animals
(rabbits, pigs, wild boar...) • Associated risk factors:
– Raw/undercooked meat intake – Meat manipulation – Homemade sausages – Game meat intake
Tei S, et al. Lancet. 2003;362:371–373 Riveiro-Barciela M, et al. J Clin Gastroenterol. 2015 ;49:165-8
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Acute hepatitis E in developed countries Increasing number of cases in Barcelona
Buti M, et al. J Hepatol 1994 Riveiro-Barciela M, et al. EASL 2015. P0624
HEV is the leading cause of acute hepatitis in Scotland
Kokki I, et al. New Microbes New Infect. 2015 15;10:6-12
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Acute hepatitis E Diagnosis
F. Rodríguez-Frias. Enferm Infecc Microbiol Clin, 2012
Meses
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Diagnosis acute hepatitis E Ig M antiHEV
ELISA against epitopes: – ORF2: Wantai, In-house assays – ORF2 and ORF3: Adaltis, Mikrogen, Genelabs
Test In-house assays
Wantai [China]
Adaltis [Eurobi,France]
Mikrogen [Menarini, Germany]
Genelabs [Singapore]
Sensitivity 98% G1 85% 87,5% 92% 82%
Specificity 78- 93% G1 99,6% 100% 96% 100%
Drobeniuc J et al. Clin Infec Dis 2010 Aggarwal R. Nat Rev Gastroenterol Hepat 2012
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Extrahepatic manifestations of HEV
Riveiro-Barciela M, et al. Ann Hepatol, 2013
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Neurologic manifestations of HEV
Dalton HR, et al. J Hepatol 2017;67(5):925-932
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Hepatitis E virus-associated neuralgic amyotrophy
Van Eijk JJJ, et al. Neurology 2017 29;89(9):909-917
57 cases with HEV 61 cases without HEV
Majority anicteric All genotype 3 (38 plasma; 1 CSF)
More likely to bilateral involvement
(80.0% vs 8.6%, p < 0.001)
More likely to damage outside the
brachial plexus (58.5% vs 10.5%, p < 0.01)
There was no difference in outcome between the 2 groups at 12 months
Need of HEV testing in all patients with neuralgic amyotrophy??
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Varón 52 años con hepatitis aguda E y neuralgia braquial
Evolución analítica y clínica
ALT (UI/mL)
ARN VHE (UI/mL)
21-sep 1-oct 13-oct
Mejoría dolor Desaparición dolor y parestesias
EMG normal
Diagnóstico
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Caso clínico 2
Varón 49 años
No hábitos tóxicos
Antecedentes: púrpura trombótica trombocitopénica (PTT)
Desde 2016 EC con caplacizumab
Enero 2017: Último episodio PTT: inducida por gripe A (plasmaféresis)
Febrero 2017: 155.000 Plaquetas/mL [150-500]
Marzo 2017:
Plaquetas 149.000/mL [150-500]
TQ 101%
Bilirrubina 5.35 mg/dL [0.3-1.2]
AST 1515 UI/mL [12-50]
ALT 991 UI/mL [8-50]
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Caso clínico 2
Ecografía abdominal: normal
Estudio autoinmunidad: negativo
AntiVHC y RNA VHC, HBsAg, IgM antiHBc: negativos
No ingesta ni manipulación de carne cruda, no viajes al extranjero...
Ingreso previo enero: corticoides, oseltamivir, plasmaféresis,
caplacizumab... DILI?
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Not all undiagnosed acute hepatitis cases are related to drugs...
Dalton HR, et al. Aliment Pharmacol Ther. 2007 15;26(10):1429-35
47 cases of hepatotoxicity
6 (13%) HEV RNA +
45 acute hepatitis E
10 (22%) firstly suspicion of hepatotoxicity
DILI HEV
Amoxi-clav. Statins
Flucloxacilin NSAIA
Chinese herbs Amoxicilin
Clorpromazin Cephalosporins
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Caso clínico 2
Ecografía abdominal: normal
Estudio autoinmunidad: negativo
AntiVHC y RNA VHC, HBsAg, IgM antiHBc: negativos
IgM VHE y ARN VHE: positivos
Traceback plasmaféresis: 1 de 99 hemoderivados utilizados positivo para ARN VHE
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HEV RNA prevalence in blood donors Country Year Author N Subjects HEV RNA
Scotland 2013 Cleland 14520 1/14520
USA 2013 Xu 1939 0/1939
Netherlands 2013 Slot 40176 1/2363
Germany 2014 Juhl 1019 1/4252
Spain 2015 Sauleda 9998 1/3332
China 2015 Ma 816 0/816
USA 2016 Stramer 18829 1/9500
Netherlands 2016 Hogema 59474 1/1321
Cleland A, et al. Vox Sang 2013;105:283-9; Xu C, et al. Transfusion. 2013;53:2505-11; Juhl D, et al. Transfusion. 2014;54:49-56; Slot E, et al. Euro Surveill. 2013 ;18(31); Sauleda S, et al. Transfusion 2015;55:972-9; Ma L, et al. The Journal of international medical research 2015;43:257-262; Stramer SL, et al. Transfusion; 2016;56(2):481-8; Hogema BM, et al. Transfusion 2016;56(3):722-8.
The Lancet. January 2014
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Hepatitis E in blood products
Hewitt PE, et al. Lancet 2014 15;384(9956):1766-73
225.000 donations within 1 year in England
78 HEV RNA + (1/2848)
Majority seronegative
16 RBC 10 Plat. (pool)
14 Plat. (aferesis) 2 plasma Transfused
subjects
Infected subjects 4 (25%) 4 (40%) 7 (50%) 2 (100%)
13/18 were immunosuppressed
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Caso clínico 2
Coagulación normal
bilirrubina 24.5 mg/dL
Concomitantemente...
Plaquetopenia
50.000/mL
Hb 10 mg/dL
Púrpura en EEII
Aumento LDH
Haptoglobina
indetectable
Actividad ADAMS-13
indetectable Brote de púrpura trombótica
trombocitopénica
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Acute hepatitis E Prognosis
• Self-limited infection in the majority of cases Poorer prognosis in developed countries Elderly people Prior liver disease
• High morbidity and mortality rates associated with
acute on chronic liver failure Mortality: 33-76% Underlying alcoholic cirrhosis Genotype 1 and 3
Péron JM. J Hepat, 2011; Dalton HR. Lancet, 2007
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Complicaciones asociadas a la infección por VHE
Complicaciones
extrahepáticas
Cronificación de la infección en sujetos inmunosuprimidos
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Development of liver fibrosis and rapid progression to cirrhosis
Solid organ and stem cell transplantion
HIV infection Haematological neoplasm and chemotherapy Immunosuppressed therapy
Chronic hepatitis E Clinical relevance
Author, year Organ Incidence
Haagsma EB, 2009 Liver 1,75%
Pischke S, 2010 Liver 2,9%
Legrand-Abravanel F, 2011 Liver, Kidney, Pancreas 5.65%
Pischke S, 2012 Heart 1,5%
Legrand-Abravanel F, 2013 Liver or Kidney 3,1%
Versluis J, 2013 Hematopoietic stem cell 2,4%
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Diagnosis of chronic hepatitis E • Cause of persistently increased ALT levels in
transplant patients, immunosuppressed or cirrhotics
• Serological tests are not useful for diagnosis
HEV RNA Transplantation
Cirrhosis HIV
Immunosuppressed
ALT Without etiology
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Treatment of chronic hepatitis E Ribavirin in transplantation
Kamar N, el al. NEJM 2014 20;370:1111-20
37 Kidney 10 Liver 5 Heart 5 Kidney-Pancreas 2 Lung
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Caso clínico 2
Remisión de la PTT tras tratamiento y curación de la hepatitis aguda e
con Ribavirina (600 mg/d durante 12 semanas)
Plat
elet
s co
unt (
109 /
L)
HEV RNA (IU
/mL)
1,E+00
1,E+01
1,E+02
1,E+03
1,E+04
0
50
100
150
200
250
300
17-3 31-3 4/4 (BL) 11/04 (W1) 18/04 (W2) 03/05 (W4) 30/05 (W8) 27/06 (EOT) 25/07 (FU4) 19/10(FU12)
Platelets count HEV RNA
Ribavirin
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Take home messages
Infección por el virus de la hepatitis E
Número creciente de casos
Más frec.: Hepatitis colestásica y pacientes mayores
Manifestaciones extrahepáticas
Normalmente autolimitada
Riesgo de cronificación en sujetos inmunosuprimidos