Hepatitis E. María Buti Hospital Universitario Valle Hebron Barcelona

Transcription

1 Hepatitis E María Buti Hospital Universitario Valle Hebron Barcelona

2 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

3 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

4 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

5 Varón 52 años con hepatitis aguda No fármacos salvo antihipertensivos Drug-induced liver injury Ecografía normal Biliar Hepatitis autoinmune Electroforesis IgG Est. AU NEGATIVO HBsAg, Ig M antihbc antivhc, RNA VHC NEGATIVOS Hepatitis aguda B o C Infecciones Hepatitis E IgM y RNA VHE POSITIVOS

6 Hepatitis E Main characteristics: Enteric transmission Epidemic Unique viral hepatitis with animal reservoir

7 Current magnitude of HEV Annual estimation (2005): 20 million acute infections 3 million symptomatic infections 70,000 deaths per year?? Chronic infections Data from GT 1 and 2, therefore it took no account of zoonotic HEV Rein DB, et al. Hepatology 2012;55:

8 Worldwide distribution of HEV Purcell RH. J Hepatol, 2008

9 Hepatitis E. Escenarios Países subdesarrollados Países desarrollados August 25, 2016 Strictly human Link with outbreaks Genotype 1 and 2 Genotype 3 and 4 Fecal-orally (contaminated water) GT 1- Asia GT 2- Africa and Mexico Human and animals No Zoonosis Blood product transfusion; Transplantation GT 3- Europe, Southeast Asia GT 4- France,Italy,Germany, Belgium (pigs), Japan

10 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: Riveiro-Barciela M, et al. J Clin Gastroenterol ;49:165-8

11 Acute hepatitis E in developed countries Increasing number of cases in Barcelona HEV is the leading cause of acute hepatitis in Scotland Buti M, et al. J Hepatol 1994 Riveiro-Barciela M, et al. EASL P0624 Kokki I, et al. New Microbes New Infect ;10:6-12

12 Acute hepatitis E Diagnosis Meses F. Rodríguez-Frias. Enferm Infecc Microbiol Clin, 2012

13 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

14 Extrahepatic manifestations of HEV Riveiro-Barciela M, et al. Ann Hepatol, 2013

15 Neurologic manifestations of HEV Dalton HR, et al. J Hepatol 2017;67(5):

16 Hepatitis E virus-associated neuralgic amyotrophy 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?? Van Eijk JJJ, et al. Neurology ;89(9):

17 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 Diagnóstico Mejoría dolor Desaparición dolor y parestesias EMG normal

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19 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: Plaquetas/mL [ ] Plaquetas /mL [ ] Marzo 2017: TQ 101% Bilirrubina 5.35 mg/dl [ ] AST 1515 UI/mL [12-50] ALT 991 UI/mL [8-50]

20 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?

21 Not all undiagnosed acute hepatitis cases are related to drugs cases of hepatotoxicity 45 acute hepatitis E 6 (13%) HEV RNA + 10 (22%) firstly suspicion of hepatotoxicity DILI Amoxi-clav. Flucloxacilin Chinese herbs Clorpromazin HEV Statins NSAIA Amoxicilin Cephalosporins Dalton HR, et al. Aliment Pharmacol Ther ;26(10):

22 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

23 HEV RNA prevalence in blood donors Country Year Author N Subjects HEV RNA Scotland 2013 Cleland /14520 USA 2013 Xu /1939 Netherlands 2013 Slot The Lancet. January /2363 Germany 2014 Juhl /4252 Spain 2015 Sauleda /3332 China 2015 Ma 816 0/816 USA 2016 Stramer /9500 Netherlands 2016 Hogema /1321 Cleland A, et al. Vox Sang 2013;105:283-9; Xu C, et al. Transfusion. 2013;53: ; Juhl D, et al. Transfusion. 2014;54:49-56; Slot E, et al. Euro Surveill ;18(31); Sauleda S, et al. Transfusion 2015;55:972-9; Ma L, et al. The Journal of international medical research 2015;43: ; Stramer SL, et al. Transfusion; 2016;56(2):481-8; Hogema BM, et al. Transfusion 2016;56(3):722-8.

24 Hepatitis E in blood products donations within 1 year in England Majority seronegative 78 HEV RNA + (1/2848) Transfused subjects 16 RBC 10 Plat. (pool) 14 Plat. (aferesis) 2 plasma Infected subjects 4 (25%) 4 (40%) 7 (50%) 2 (100%) 13/18 were immunosuppressed Hewitt PE, et al. Lancet ;384(9956):

25 Caso clínico 2 Coagulación normal bilirrubina 24.5 mg/dl Concomitantemente... Plaquetopenia /mL Hb 10 mg/dl Aumento LDH Haptoglobina indetectable Púrpura en EEII Actividad ADAMS-13 indetectable Brote de púrpura trombótica trombocitopénica

26 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

27 Complicaciones asociadas a la infección por VHE Complicaciones extrahepáticas Cronificación de la infección en sujetos inmunosuprimidos

28 Chronic hepatitis E Clinical relevance Development of liver fibrosis and rapid progression to cirrhosis Solid organ and stem cell transplantion 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% HIV infection Haematological neoplasm and chemotherapy Immunosuppressed therapy

29 Diagnosis of chronic hepatitis E Cause of persistently increased ALT levels in transplant patients, immunosuppressed or cirrhotics Serological tests are not useful for diagnosis Transplantation Cirrhosis HIV Immunosuppressed ALT Without etiology HEV RNA

30 Treatment of chronic hepatitis E Ribavirin in transplantation 37 Kidney 10 Liver 5 Heart 5 Kidney-Pancreas 2 Lung Kamar N, el al. NEJM ;370:

31 Caso clínico 2 Platelets count HEV RNA Platelets count (10 9 /L) Ribavirin 1,E+04 1,E+03 1,E+02 1,E+01 HEV RNA (IU/mL) /4 (BL) 11/04 (W1) 18/04 (W2) 03/05 (W4) 30/05 (W8) 27/06 (EOT) 25/07 (FU4) 19/10 (FU12) 1,E+00 Remisión de la PTT tras tratamiento y curación de la hepatitis aguda e con Ribavirina (600 mg/d durante 12 semanas)

32 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