[HEV and transfusion-recipient risk]. / Virus de l'hépatite E et risque de transmission par transfusion.

HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60 % of immunocompromised patients infected with HEV genotype 3. Extra-hepatic manifestations such as neurological and renal manifestations have been reported. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.

Epidemiology of hepatitis E virus infection during pregnancy in Benin.

OBJECTIVES: Hepatitis E virus (HEV) is the cause of enterically transmitted non-A, non-C hepatitis (an infection that is particularly severe during pregnancy) in tropical and subtropical countries. As there are no published data concerning the prevalence of HEV antibodies in Benin, their presence was investigated in pregnant women undergoing routine HIV screening in a rural area in northern Benin and in pregnant women with acute non-A, non-C hepatitis. METHODS: A total of 278 serum samples were collected from asymptomatic pregnant women in 2011 were tested for HEV and hepatitis A virus (HAV) antibodies, and the HEV IgM-positive samples were further tested for HEV-RNA. A further seven samples of pregnant women with acute non-A, non-C hepatitis collected during episodes of acute hepatitis in 2005 were also analysed. RESULTS: Of the 278 samples collected in 2011, 16.19% were positive for HEV IgG and 1.44% for HEV IgM (none positive for HEV-RNA), and 99.64% were positive for total HAV antibodies (none positive for HAV IgM). Six of the seven samples collected in 2005 were positive for HEV IgG and IgM, and two were also positive for HEV-RNA. CONCLUSIONS: The circulation of HEV infection is significant among pregnant women in Benin, in whom the consequences may be fatal.

Hepatitis E seroprevalence in inflammatory bowel disease.

BACKGROUND AND AIMS: Several cases of chronic infection by hepatitis E virus (HEV) in immunocompromised patients have been described recently. Patients with inflammatory bowel disease (IBD) are frequently immunocompromised because of the disease itself or due to therapy. Our aims were to determine HEV seroprevalence in patients with IBD and to detect possible chronic forms. METHODS: We prospectively selected a random sample of 87 patients from our local IBD clinic database at the Gastroenterology Service, Hospital Ramón y Cajal, in Madrid, Spain. Patients completed an oral epidemiologic interview. Anti-HEV IgG and IgM antibodies and HEV-RNA were determined. Medical records were reviewed, focusing on drug exposure. RESULTS: We included 87 patients, with a mean age of 44.7 years (SD 16) and a mean of 10.4 years (SD 8.4) with IBD. Fifty-seven percent were diagnosed with Crohn's disease, 41.4% with ulcerative colitis and 1.1% with unclassified IBD. A total of 41.4% had received systemic glucocorticoids for more than 3 months, 32.2% had been treated with thiopurines, 16.1% with biological drugs, and 3.4% with methotrexate. Anti HEV-IgM was determined in 75 patients and IgG in 80, and were positive in 2.7% and 1.3%, respectively. HEV-RNA was analyzed in a random subset of 46 patients, and all determinations were negative. Therefore, no case of chronic HEV infection was detected. CONCLUSIONS: We found a low HEV seroprevalence of just 1.14% in patients with IBD, similar to that in the general population. This could be due to the lower degree of immunosuppression in this group, or to different dietary habits.

Valproate, risperidone, and paliperidone: A case of valproate-induced hyperammonemic encephalopathy.

Hyperammonemia is a well-known adverse effect of valproate that can progress to a potentially fatal condition known as valproate-induced hyperammonemic encephalopathy (VHE). VHE is more common when valproate is used in combination therapy with other antiepileptic medications. A growing number of case reports have pointed to a possible interaction with the antipsychotic risperidone leading to an increased risk of VHE. We present a case of VHE in which a 20-year-old male patient with bipolar affective disorder developed VHE when on concomitant valproate, risperidone, and paliperidone palmitate. On the seventh day of treatment with oral risperidone, oral divalproex sodium was added. Intramuscular paliperidone palmitate was initiated on day 13, and oral risperidone was discontinued after the second loading dose on day 16. The following day, the patient displayed worsening psychomotor retardation, swaying gait, drowsiness, and vomiting. The patient was found to have hyperammonemia and transferred to the emergency department for treatment of suspected VHE.

Hyperammonemia and hepatic status during valproate therapy.

The present study was conducted to assess correlation of ammonia levels with valproate levels in epileptic patients presenting with valproate toxicity and also whether liver enzymes and ammonia levels could serve as biochemical marker of valproate toxicity. 100 patients with epilepsy who had received valproate therapy for more than 12 months and had presented with valproate toxicity and 100 controls were included in the study. The serum valproate, ammonia and liver enzymes were measured in these subjects. In patients with valproate toxicity, the mean level of serum valproate was 110.91 ± 28.68 mg/dL (therapeutic range 50-100 mg/dL). Serum ammonia was higher (86.37 ± 39.90 µg/dL) in patients with valproate toxicity compared to controls (68.73 ± 30.07 µg/dL). Out of 100 patients, only 37 patients had serum valproate level > 120 mg/dL and 22 patients had raised levels of valproate as well as ammonia. Age < 30 years and serum ammonia > 69 µg/dL is risk factors for valproate toxicity. Serum ammonia, liver enzymes should be regularly investigated in patients on valproate therapy for early diagnosis of valproate toxicity.

Estimation of the hepatitis E assay-dependent seroprevalence among Croatian blood donors.

BACKGROUND: Seroprevalence of hepatitis E virus (HEV) in blood donors presenting to the Croatian Institute of Transfusion Medicine was assessed with 4 available tests (3 ELISA tests and 1 immunoblot (IB) test). MATERIALS AND METHODS: In October and November 2014, a total of 1,036 serum samples of blood donors were collected for the study. Samples were primarily tested for total HEV antibodies by Dia.Pro HEV Ab test (a). All reactive samples were tested by ELISA tests: Dia.Pro HEV IgG (b) and IgM (c), Mikrogen recomWell HEV IgG_old (d) and IgM_old (e), recomWell HEV IgG_new (f) and IgM_new (g), and IB Mikrogen recomLine HEV IgG (h) and IgM (i). HEV IgM reactive samples also positive by the IB were further tested for HEV RNA. RESULTS: There were 21.5% of samples reactive for total HEV antibodies (a). Seroprevalence of HEV IgG according to the b, d, f and h tests was 20.2%, 9.6%, 18.1% and 17.8%, respectively. Seroprevalence of HEV IgM according to the c, e, g and i tests was 4.4%, 1.5%, 2.0% and 1.7%, respectively. Out of 46 HEV IgM (Dia.Pro HEV IgM) positive samples, 18 (39.1%) were also positive by IB. HEV RNA was not detected in any of those samples. There was a significant association between age and HEV seroprevalence (P<0.001). CONCLUSION: Different HEV antibody detection assays showed a high HEV IgG seroprevalence in Croatian blood donors. Among HEV IgG and HEV IgM positive samples HEV RNA was not detected.

HEV and transfusion-recipient risk.

HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60% of immunocompromised patients infected with HEV genotype 3. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.

Virus de la hepatitis E

Resumen El virus de la hepatitis E (VHE) es uno de los principales agentes etiológicos de hepatitis entérica en el mundo. En países en vía de desarrollo, la seroprevalencia oscila entre 20 y 50% y en países desarrollados entre 4,4 y 21%. Clínicamente los casos de infección por VHE en individuos inmunocompetentes cursan como una hepatitis viral aguda auto limitada; por el contrario, en mujeres embarazadas, individuos receptores de trasplantes de órganos e individuos que conviven con el virus de la inmunodeficiencia humana (VIH), la infección puede manifestarse como una hepatitis crónica y grave. En América Latina, sólo Brasil y Argentina reportan cifras en individuos que conviven con el VIH. Se requieren más estudios en nuestra región que permitan determinar la prevalencia del VHE en individuos inmunosuprimidos, donantes de sangre y población general para adoptar medidas que garanticen un diagnóstico oportuno, acceso a la atención y el control de la transmisión.

Abstract The hepatitis E virus (HEV) is one of the main etiological agents of enteric hepatitis in the world. In developing countries its sero-prevalence ranges from 20 to 50% and in developed countries from 4.4% to 21%. Clinically, cases of HEV infection in immunocompetent individuals present as self-limited acute viral hepatitis; conversely, in pregnant women, transplanted individuals, and individuals living with the human immunodeficiency virus (HIV), the infection can manifest as chronic and severe hepatitis. In Latin America, only Brazil and Argentina report figures for individuals living with HIV. More studies are required in our region to determine the prevalence of HEV in immunosuppressed individuals, blood donors, and the general population to adopt measures that guarantee timely diagnosis, access to care, and control of transmission.

[Hepatitis E virus: Blood transfusion implications]. / Virus de l'hépatite E, implications en transfusion sanguine.

Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations.

[Assessment of a transfusion emergent risk: the case of HEV]. / Estimation d'un risque transfusionnel émergent: l'exemple du VHE.

BACKGROUND: The risk assessment for blood transfusion is an essential step that must precede any screening strategy of a pathogen transmitted by transfusion. After several cases of HEV transmission by transfusion in France, a risk assessment for this virus was performed. METHODS: We used a method based on the prevalence of HEV-RNA in plasmas collected for the preparation of SD-plasma. To estimate the rate of HEV-RNA positive among all blood donations, data on SD-plasma were adjusted on the following HEV risk factors: gender, age group and region of residence. We assumed that HEV risk factors were the same in plasma donors and whole blood donors. RESULTS: Among 57,101 plasma donations tested for HEV-RNA in 2013, 24 were positive (crude rate of 4.2 per 10,000 donations). After adjustment, the total number of HEV-RNA positive blood donations was estimated at 788, accounting for a rate of 2.65 per 10,000 donations (95% CI: 1.6-3.7) or 1 in 3800 donations (1 in 6,200-1 in 2,700). This rate was 12 times higher in men than in women, increased with age, and varied according to region of residence. CONCLUSION: The risk of blood donation contamination by HEV has been estimated to be 1 in 3800 donations in 2013. An essential input is still missing to assess now the risk in recipients: the minimum infectious dose. Furthermore, the risk in recipients has to be analyzed according to characteristics of transfused patients: presence of anti-HEV immunity, existence of chronic liver disease or immunodeficiency.

Detección del genotipo 1d del virus de la hepatitis E en pacientes con sospecha de hepatitis viral aguda, Cuba 2013 / Detection of hepatitis E virus genotype 1d in patients with suspect of acute viral hepatitis in Cuba during 2013

Resumen Introducción El virus de la hepatitis E (VHE) se transmite, principalmente, por vía fecal-oral y es una de las principales causas de hepatitis viral aguda (HVA) en el mundo. En Cuba, a pesar de que este virus tiene un comportamiento endémico, no se relaciona a este patógeno al presentarse una hepatitis viral de trasmisión entérica. Objetivo Teniendo en cuenta que el VHE y el virus de la hepatitis A (VHA) comparten rutas de transmisión, nos propusimos estimar la incidencia de ésta infección (VHE), en muestras que se recibieron de todo el país durante el año 2013, cuyo criterio de inclusión fue la indicación médica de IgM anti-VHA. Materiales y Métodos Se empleó la RT-PCR específica para el marco abierto de lectura 2 (MAL2), con el propósito de detectar el ARN-VHE en las 422 muestras estudiadas. Los productos amplificados fueron purificados, secuenciados y analizados filogenéticamente con el programa MEGA6. Resultados La presencia de ARN-VHE se detectó en 8,53% (36/422) de las muestras estudiadas. El mayor índice de positividad se identificó en la región occidental del país, específicamente en La Habana con 5,45% (23/422). En total se diagnosticaron 5,21% (22/422) muestras positivas al marcador de IgM VHA; la detección simultánea de marcadores del VHA-VHE fue 13,88% (5/36). Los resultados demuestran una mayor incidencia del VHE con respecto al VHA (8,53% vs 5,21%) y el análisis filogenético mostró la circulación del genotipo 1, subgenotipo 1d del VHE. Conclusiones Se corroboró la endemicidad del VHE en nuestro país y, por primera vez, se identificó el subgenotipo 1d, variante africana asociada a casos esporádicos y brotes de hepatitis E.

Abstract Introduction Hepatitis E virus (HEV) is mainly transmitted by the fecal-oral route and is one of the most important causes of acute viral hepatitis (AVH) around the world. In Cuba, Despite of endemic behavior of HEV in Cuba, its causality is not associated when a picture of enteric acute hepatitis is suspected. Objective Taking into account the common transmission route of both HEV and HAV, our aim was to estimate the incidence of HEV infection in sera samples received throughout the country during 2013 where the IgM anti-HAV test was required by the Clinician. Materials and Methods A specific RT-PCR for open reading frame 2 (ORF2) was used to detect RNA-HEV in 422 sera. The amplified products corresponding to ORF2 were purified, sequenced and phylogenetically analyzed using MEGA6 software program. Results RNA-HEV was detected in 8.53% (36/422) of the samples. The highest rate of positivity was identified in the Western region of the country, specifically in Havana 5.45% (23/422). IgM anti-HAV was detected in 5.21% (22/422) and simultaneous detection of both HAV and HEV was found in 13.88% (5/36) of the samples. The results showed a higher incidence of HEV with respect to HAV (8.53% vs 5.21%) and phylogenetic analysis showed the circulation of genotype 1, subgenotype 1d of the HEV. Conclusions This study corroborated the endemicity of HEV and for the first time the subgenotype 1d, the African variant strain associated to outbreak of hepatitis E, is reported in viral hepatitis cases in Cuba.

El virus de hepatitis E en los animales domésticos: Una revisión / Hepatitis E virus in domestic animals: A review

El virus de la Hepatitis E (VHE) es un patógeno emergente, fue originalmente identificado como el agente de transmisión de hepatitis entérica No-A, No-B, e identificado en cerdos y en humanos. La infección por el virus de la hepatitis E (VHE), está ganando la atención mundial, debido a la creciente car ga de la enfermedad en los países de baja endemicidad, en términos de morbilidad y mortalidad, sino también debido a los avances recientes en la virología molecular y la epidemiología de esta emergente patógeno. La propagación del VHE infección puede ser descrita como la evolución de una zoonosis hacia una infección humana establecida. Como se sabe por otros virus, tales como el virus de la inmunodeficiencia hu mana o de los virus de influenza, que cruzan las barreras de las especies de animales a los seres humanos, es un fenómeno recurrente. Aunque lenta al principio, una vez que el virus se ha adaptado a los humanos, la propagación de persona a persona puede proceder muy rápidamente. Las cepas del VHE aisladas en humanos tienen una estrecha relación genética con cepas halladas en cerdos, ratas y pollos. Se han determinado anticuerpos anti-VHE en bovinos, caninos, felinos, primates y roedores. El virus de Hepatitis E es de gran importancia desde el punto de vista de la salud pública. Los animales domésticos y otras especies se pueden comportar como reservorios potencialmente infeccioso. El riesgo de infección para el humano es inminente ya sea por consumo de alimentos de origen animal contaminado, aguas contaminadas y transmisión directa oral-oral, oral-fecal. Alimentos de origen animal sin la inspección sanitaria que garanticen la calidad e inocuidad deben ser considerados como un elemento infeccioso potencial a nivel de mataderos industriales y sobre toda la cadena de comercialización.

Hepatitis E virus (HEV) is an emerging pathogen, was originally identified as the agent of transmission of enteric hepatitis Non-A, Non-B, identified in pigs and humans. Hepatitis E virus (HEV), Infection is gaining worldwide attention because of the increasing burden of disease in low endemic countries in terms of morbidity and mortality, but also because of recent advances in the molecular virology and epidemiology of this emerging pathogen. The spread of HEV infection can be described as the evolution of a zoonosis to established human infection. As known from other viruses such as human immunodeficiency virus or influenza virus crossing the species barrier from animals to humans is a recurring phenomenon. Although slow at first, once the virus has adapted to humans, spread from person to person can come very quickly. HEV strains iso lated in humans are closely related genetically to strains found in pigs, rats and chickens. Have been gi - ven an ti-HEV antibodies in cattle, dogs, cats, primates and rodents. Hepatitis E virus is of great importance from the standpoint of public health, the impact on the liver and pregnancy. Pets and other species can behave as re - servoirs potentially infectious. The risk of infection for humans is im mi nent either through consumption of con - taminated food of ani mal origin, contaminated water and direct oral-oral trans mission, fecal-oral. Animal foods without health inspections to ensure quality and safety must be considered as a potential infectious element-level slaughterhouses and the entire supply chain.

Molecular characterization of swine hepatitis E virus from Southeastern Brazil

Despite serological evidences of presence of hepatitis E virus (HEV) in humans or other animals, until this study the virus had not been detected and molecular characterization of the isolate that circulates in Brazil had not been described. Thus, we collected stool samples of young pigs and tested for presence of HEV RNA by RT-PCR, using primers for partial amplification of ORF2 sequence. Phylogenetic analysis with sequence obtained from the amplified products revealed that the HEV isolate identified here was most closely related to HEV isolates of genotype 3, which is commonly detected in HEV infected pigs. Nucleotide sequence analyses carried out with the entire amplified fragment, ORF2/ORF3 overlapping and ORF2 non-overlapping sequences showed highest identities with the US isolate of genotype 3. Similarly, amino acid sequence analyses done with the entire amplified fragment, ORF2 non-overlapping, ORF2 and ORF3 overlapping sequences also showed highest identities with the genotype 3 isolate. Presence, in Brazil, of HEV of genotype 4, which also infects pigs, as well as HEV strains that infect humans still remain to be detected and characterized.

Apesar de evidências sorológicas da presença do vírus da hepatite E (VHE) em humanos ou outros animais, até o presente estudo o vírus não havia sido detectado e a caracterização molecular da cepa que circula no Brasil não havia sido descrita. Assim, amostras de fezes de porcos jovens foram colhidas e analizadas quanto a presença do ARN do VHE por RT-PCR, utilizando-se oligonucleotídeos para amplificação da seqüência parcial do ORF2 viral. Análise filogenética realizada com a seqüência obtida dos produtos amplificados revelou que a cepa encontrada apresentou relação próxima com cepas do genótipo 3 que são detectadas com freqüência em porcos. Análises das seqüências nucleotídicas realizadas com todo o segmento amplificado, com somente o segmento sobreposto do ORF2/ORF3 e aquele sem sobreposição do ORF2, em comparação com isolados de genótipos conhecidos, mostraram maior identidade com o isolado encontrado nos Estados Unidos (US) do genótipo 3. De maneira semelhante, análises da seqüência de aminoácidos realizadas com os mesmos segmentos também mostraram maior identidade com o isolado de genótipo 3. Presença ou não do vírus de genótipo 4, que também infecta porcos, ainda necessita ser verificada. Da mesma forma, cepas do VHE que infectam humanos ainda necessitam ser detectadas e caracterizadas.