HEV infection in two referral centers in Spain; epidemiology and clinical outcomes

doi:10.1016/j.jcv.2014.12.017

Journal of Clinical Virology

Volume 63, February 2015, Pages 76-80

https://doi.org/10.1016/j.jcv.2014.12.017 Get rights and content

Highlights

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We characterized the epidemiological pattern of HEV infection and clinical outcomes.
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Low incidence of HEV in transplant recipients despite risk factors.
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4/5 cases in transplant recipients failed to clear the virus and evolved to chronicity.
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Relapse after RBV treatment occurred in a patient with combined immunodeficiency.
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First described G3-HEV-induced agranulocytosis in a immunocompetent patient.

Abstract

Background and objectives

Hepatitis E virus (HEV) is one of the major causes of icteric hepatitis worldwide. In industrialized countries it is considered an emerging disease, as a growing number of autochthonous cases have been reported in recent years. Occasional extrahepatic manifestations have been described in the setting of HEV infection.

Study design

To characterize the epidemiological pattern and clinical outcomes of new cases of HEV infection diagnosed in two referral centers during the period 2011–2013.

Results

During the study period, four cases of self-limited acute hepatitis E after travel to endemic areas were recorded, as well as five cases of HEV infection after solid organ transplantation. Four patients failed to spontaneously clear the virus and received ribavirin monotherapy; all of them had HEV genotype-3. Ribavirin was effective in inhibiting HEV replication, although in one patient a virological relapse occurred after the end of therapy. Finally, we report a case of HEV-genotype-3 related agranulocytosis in an immunocompetent patient, resulting in a fatal outcome; this is the first case reported of its kind.

Conclusion

Diagnosis of HEV infection needs to be taken into consideration in patients with acute or chronic hepatitis in whom other etiologies have been excluded. Although hematological complications related to acute HEV infection are infrequent, these may affect any of the bone marrow series, even after viral clearance.

Section snippets

Background

Hepatitis E virus (HEV) is the causal agent of hepatitis E. Currently, it is considered to be the main cause of enterically transmitted hepatitis worldwide [1], [2]. In developing countries, HEV genotypes 1–2 are transmitted through water and are associated to epidemic outbreaks, affecting mostly young adults. On the contrary, genotypes 3–4 have been isolated not only in humans but also in animals, supporting the zoonotic nature of the infection responsible for most of the sporadic cases in

Objectives

To characterize the epidemiological pattern of HEV infection in two referral centers in Barcelona, with particular focus on recipients of solid organ transplants, and to analyze the clinical outcomes of confirmed HEV infection in our center.

Study design

Between 2011–2013, the Microbiology Department in our hospital received 392 samples to assess the presence of HEV infection. Approximately, half of the suspected cases had been attended in the Liver Unit, including those from another referral center. HEV was suspected in cases of acute hepatitis in patients with epidemiological risk factors (i.e., travel to endemic areas). After the first case of HEV infection in a liver transplant recipient in our center (2011), a diagnostic protocol was

Results

From 392 tested samples, isolated anti-HEV IgG was detected in twenty-three patients (6%); suggesting a past contact with HEV. Additionally, HEV-RNA was detected in ten patients (2.5%). The remaining patients did not present any serological or virological evidence of HEV infection.

Conclusions

HEV infection is a major global health problem that causes significant morbidity and mortality worldwide. However, in industrialized countries, zoonotic transmission seems to be the major cause of HEV infections [3]. During a three-year period we detected 10 cases of HEV. These included 5 cases diagnosed in solid organ transplant recipients, where a prospective diagnostic protocol was initiated after the first case of HEV infection, reported in 2011. In transplant recipients HEV genotype-3 was

Conflict of interest

The authors declare no conflict of interest.

Funding

X. Forns received support in part by grants from Instituto de Salud Carlos III (PI11/01907), Ministerio de Economía y Competitividad, co-funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. X. Forns also received a grant from the Roche Organ Transplantation Research Foundation (ROTRF, CI: 442035057).

Competing interests

None.

Ethical approval

The study was approved by local Ethics Committee and patients signed informed written consent.

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Hepatitis E. Epidemiology and clinical relevance
2022, FMC Formacion Medica Continuada en Atencion Primaria
Puntos para una lectura rápida
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  La transmisión de la hepatitis E suele ser por vía fecal-oral.
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  Actualmente, se sabe que el VHE es endémico en la mayoría de los países industrializados debido en gran parte a una infección zoonótica, representando la causa más común de hepatitis viral aguda en muchos países europeos. El principal reservorio en la mayoría de los países es el cerdo.
- •
  La mayoría de los pacientes se recuperan espontáneamente, pero las mujeres embarazadas tienen un mayor riesgo de padecer una hepatitis fulminante y muerte.
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  El genotipo 3 del VHE puede causar hepatitis crónica en pacientes inmonosuprimidos.
- •
  Se debe sospechar la hepatitis E en viajeros en regiones endémicas, y los trabajadores que entran en contacto cercano con animales infectados por el virus. En estos casos se deben hacer pruebas de IgM anti-VHE. Además, la detección de RNA-VHE permite establecer la replicación viral y su caracterización genotípica posterior.
- •
  No existe un tratamiento específico. Se deben de prevenir la infección con el saneamiento y la adecuación de las aguas potables. Extremar la higiene personal y la correcta manipulación de los alimentos y evitar el consumo de carne poco cocida o cruda. Se debe de considerar el uso de ribavirina para la hepatitis E crónica. La inmunización con la vacuna solo está disponible en China.
Hepatitis A and E in the Mediterranean: A systematic review
2022, Travel Medicine and Infectious Disease
Citation Excerpt :
The full texts of 518 articles were assessed and 417 articles were excluded because they were irrelevant to the aim of this systematic review. Finally, 101 studies met the inclusion criteria and were included in this systematic review [20–107]. Fig. 1 provides details concerning the study selection process.
Hepatitis A (HAV) and Hepatitis E (HEV) considered to be major public health threats worldwide. Although, both infections are more common in developing countries, an increased number of HAV and HEV cases have been reported in developed countries. This systematic review analyzes epidemiological profiles of HAV and HEV in the Mediterranean countries. By using PRISMA guideline, we searched for articles from 2010 to 2020 referring HAV and HEV outbreaks from online databases: Scopus, PubMed and Springerlink. From 33265 unique publications initially captured, data was extracted from 101 articles investigating country and year of outbreak, transmission mode, vehicle of infection, mean age and sex of patients, symptoms reported, vaccination applied and diagnostic method. Our results indicate that occurrence of HAV and HEV in Mediterranean countries had increased with main transmission vehicle reported as food or water and transmission point as refugee camps. More results (countries, differences, other characteristics). Thus, public health authorities should give a priority to face up challenges regarding the prevalence of both viruses and control strategies to prevent upcoming outbreaks.
Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires
2020, Journal of Clinical Virology
Citation Excerpt :
Data from these studies should be carefully interpreted due to their retrospective design or the inclusion of non-representative populations. For example, a Spanish study retrospectively examined serum samples of the Microbiology Department from patients with acute hepatitis referred for HEV evaluation and reported a 2.5 % acute HEV prevalence [21]. Another study from Colombia analyzed 40 consecutive patients with acute viral hepatitis and identified 9 (22.5 %) cases with acute HEV [20].
Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. Objectives: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). Study design: We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. Results: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25–5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. Conclusions: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients
Practical guidelines for examination of adults with asymptomatic hypertransaminasaemia
2017, Gastroenterologia y Hepatologia
Las causas de elevación sostenida de las transaminasas séricas en pacientes adultos asintomáticos son muy variadas, tanto hepáticas como extrahepáticas, y hace falta una sistemática estandarizada para alcanzar el diagnóstico etiológico, orientada a descartar en primer lugar las causas más frecuentes, hepatitis crónica, viral o autoinmune, enfermedades metabólicas y hepatopatías tóxicas. Diversos patrones bioquímicos, que tienen en cuenta los valores de cada transaminasa, de los enzimas de colestasis, de los enzimas musculares, de la ferritina y de la ceruloplasmina, así como el resultado de la determinación del proteinograma y de los autoanticuerpos permitirán reconocer la mayoría de causas. En los casos sin diagnóstico mediante métodos no invasivos estará justificada la práctica de una biopsia hepática.
The causes of sustained elevation of serum transaminases in asymptomatic adults, both hepatic and extrahepatic, are varied. In order to reach an aetiological diagnosis, a standardized protocol should be applied, aimed firstly at ruling out the most common causes, such as chronic hepatitis (viral or autoimmune), metabolic diseases, and toxic liver diseases. Several biochemical patterns, which take into account transaminase, cholestatic enzyme, muscle enzyme, ferritin and ceruloplasmin levels, as well protein electrophoresis and autoantibody measurement, will identify most causes. In cases in which a diagnosis cannot be reached with the use of these non-invasive methods, a needle liver biopsy will be justified.
Acute hepatitis due to hepatitis E virus after raw meat consumption
2017, Gastroenterologia y Hepatologia
Hepatitis E Virus in the Iberian Peninsula: A Systematic Review
2023, Food and Environmental Virology

View all citing articles on Scopus

View full text

HEV infection in two referral centers in Spain; epidemiology and clinical outcomes

Highlights

Abstract

Background and objectives

Study design

Results

Conclusion

Section snippets

Background

Objectives

Study design

Results

Conclusions

Conflict of interest

Funding

Competing interests

Ethical approval

Infect. Genet. Evol.

J. Hepatol.

Am. J. Transplant.

J. Hepatol.

Gastroenterol. Hepatol.

Vet. Microbiol.

Ann. Hepatol.

J. Clin. Virol.

Hepatitis E

N. Engl. J. Med.

Epidemiology of hepatitis E: current status

J. Gastroenterol. Hepatol.

Hepatitis E virus and chronic hepatitis in organ-transplant recipients

N. Engl. J. Med.