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The global distribution of hepatitis E virus (HEV) is attributed to its capacity to spread through several routes of transmission; hemodialysis has gained increased amounts of attention in recent years. Although Mexico is considered a hyperendemic region for hepatitis E, no HEV surveillance is performed in the country. The frequency of HEV in hemodialysis (HD) patients has not been determined. Herein, we conducted a cross-sectional single-center analytical study including 67 serum samples from HD patients. Anti-HEV IgG and IgM antibodies and the viral genome were determined; partial regions within the HEV genome were sequenced for further phylogenetic analysis. Globally, 14.9% of the tested patients exhibited reactivity for IgG antibodies against HEV, and none showed reactivity to IgM. A total of 5.9% of the samples showed HEV genome amplification, and sequencing confirmed the identity of genotype 3; subsequent analysis of positive cases revealed two acute cases and chronic hepatitis E infection in one patient. Notably, the chronic patient was negative for anti-HEV IgG antibodies. Our findings highlight the importance of viral genome testing in HD patients and the need to establish guidelines for HEV detection in Mexico.
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Hepatitis E virus (HEV) exhibits tropism toward hepatocytes and thus affects the liver; however, HEV may also affect other tissues, including the heart, kidneys, intestines, testicles, and central nervous system. To date, the pathophysiological links between HEV infection and extrahepatic manifestations have not yet been established. Considering that HEV infects multiple types of cells, the direct effects of virus replication in peripheral tissues represent a plausible explanation for extrahepatic manifestations. In addition, since the immune response is crucial in the development of the disease, the immune characteristics of affected tissues should be revisited to identify commonalities explaining the effects of the virus. This review summarizes the most recent advances in understanding the virus biology and immune-privileged status of specific tissues as major elements for HEV replication in diverse organs. These discoveries may open avenues to explain the multiple extrahepatic manifestations associated with HEV infection and ultimately to design effective strategies for infection control.
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Vírus da Hepatite E , Hepatite E , Humanos , Privilégio Imunológico , BiologiaRESUMO
Hepatitis E virus (HEV) is the major cause of acute viral hepatitis worldwide. This virus is responsible for waterborne outbreaks in low-income countries and zoonosis transmission in industrialized regions. Initially, considered self-limiting, HEV may also lead to chronic disease, and evidence supports that infection can be considered a systemic disease. In the late 1980s, Mexico became a hot spot in the study of HEV due to one of the first virus outbreaks in Latin America related to enterically transmitted viral non-A, non-B hepatitis. Viral stool particles recovered from Mexican viral hepatitis outbreaks represented the first identification of HEV genotype (Gt) 2 (Gt2) in the world. No new findings of HEV-Gt2 have been reported in the country, whereas this genotype has been found in countries on the African continent. Recent investigations in Mexico have identified other strains (HEV-Gt1 and -Gt3) and a high frequency of anti-HEV antibodies in animal and human populations. Herein, the potential reasons for the disappearance of HEV-Gt2 in Mexico and the advances in the study of HEV in the country are discussed along with challenges in studying this neglected pathogen. These pieces of information are expected to contribute to disease control in the entire Latin American region.
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Hepatite C , Vírus da Hepatite E , Hepatite E , Animais , Humanos , Vírus da Hepatite E/genética , México/epidemiologia , Hepatite E/epidemiologia , GenótipoRESUMO
In the late 1970s, 52,000 pregnant women died in Kashmir, India [...].
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INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is not routinely screened in blood banks in low- and middle-income countries, and no specific biomarkers of exposure to this virus have yet been identified. We aimed to identify HEV seropositivity and detect virus RNA among blood donors from Mexico to further correlate risk factors related to infection and levels of interleukin-18 (IL-18) and interferon-gamma (IFN-γ) as potential biomarkers. MATERIALS AND METHODS: This cross-sectional, single-center study included 691 serum samples of blood donors obtained in 2019. Anti-HEV IgG and IgM antibodies were detected in sera and the viral genome was screened in pooled samples. A statistical comparison of risk factors for infection, demographic and clinical features was performed; IL-18 and IFN- γ values were tested in sera. RESULTS: Of all the individuals, 9.4% were positive for anti-HEV antibodies and viral RNA detection was confirmed in one of the pools positive for anti-HEV. From the analysis of risk factors, age and having pets were statistically significant for anti-HEV antibody detection. Seropositive samples showed significantly higher IL-18 concentrations relative to samples from seronegative donors. Interestingly, IL-18 values were similar when HEV seropositive samples were compared to samples from clinically acute previously confirmed HEV patients. CONCLUSIONS: Our findings highlight the need to follow up on HEV in blood banks in Mexico and underscore that IL-18 could represent a biomarker of HEV exposure.
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Vírus da Hepatite E , Hepatite E , Humanos , Biomarcadores , Doadores de Sangue , Estudos Transversais , Anticorpos Anti-Hepatite , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Imunoglobulina M , Interleucina-18 , México/epidemiologia , RNA Viral , Estudos SoroepidemiológicosRESUMO
Introducción: en México, las hepatitis virales son de notificación epidemiológica obligatoria, pero no existe un sistema especial de vigilancia. La información disponible se limita a la distribución por edad y sexo. Ante la alerta de casos de hepatitis aguda grave de etiología desconocida, en la Unión Europea el Consejo Nacional de Vigilancia Epidemiológica (CONAVE) alertó al Sistema Nacional de Salud (SNS) para la atención y vigilancia de estos casos. Desarrollo: la hipótesis más convincente sobre la etiología está relacionada con una respuesta inmunitaria exacerbada que es mediada por superantígenos relacionados con la proteína espiga del SARS-CoV-2, activados por una infección por adenovirus que desencadena una respuesta de linfocitos T que provoca apoptosis de hepatocitos. Con base en la presentación clínica (niños menores de 16 años, con diarrea, dolor abdominal, ictericia, vómito e hipertransaminasemia) se han diseñado definiciones operacionales para su identificación y notificación al Sistema Nacional de Vigilancia Epidemiológica (SINAVE). Hasta junio del 2022, se han identificado 56 casos en México. Conclusiones: este brote de hepatitis representa un reto para el SINAVE. Es necesario incluir la identificación de adenovirus en el algoritmo diagnóstico de enfermedad respiratoria viral, implementar un sistema especial de vigilancia epidemiológica de hepatitis virales y sensibilizar a los profesionales sanitarios en el tema.
Introduction: In Mexico viral hepatitis requires mandatory epidemiological notification, but there is no special surveillance system. Available information is limited to distribution of cases by age and sex. Given the alert of cases of severe acute hepatitis of unknown etiology in the European Union, the National Council for Epidemiological Surveillance (Consejo Nacional de Vigilancia Epidemiológica) alerted the entire National Health System to care for and monitor these cases in Mexico. Development: The most convincing hypothesis is an exacerbated immune response mediated by superantigens related to the spike protein of SARS-CoV-2, activated by adenovirus infection that ends in a response of T lymphocytes that causes apoptosis of hepatocytes. Based on clinical presentation (children under 16 years of age, with diarrhoea, abdominal pain, jaundice, vomiting and increase in transaminases) the operational case definitions have been designed for their timely identification and notification to the National System of Epidemiological Surveillance (Sistema Nacional de Vigilancia Epidemiológica). Until June 2022, 56 cases have been identified in Mexico. Conclusions: This hepatitis outbreak represents a challenge for the National System of Epidemiological Surveillance. It is necessary to include the identification of adenovirus in the diagnostic algorithm for viral respiratory disease, to implement a special epidemiological surveillance system for viral hepatitis, and to sensitize health professionals on this subject.
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Humanos , Masculino , Feminino , Hepatite C/etiologia , Hepatite A/etiologia , Hepatite B/etiologia , MéxicoRESUMO
Scavenger receptors (SR) are not only pattern recognition receptors involved in the immune response against pathogens but are also important receptors exploited by different virus to enter host cells, and thus represent targets for antiviral therapy. The high mutation rates of viruses, as well as their small genomes are partly responsible for the high rates of virus resistance and effective treatments remain a challenge. Most currently approved formulations target viral-encoded factors. Nevertheless, host proteins may function as additional targets. Thus, there is a need to explore and develop new strategies aiming at cellular factors involved in virus replication and host cell entry. SR-virus interactions have implications in the pathogenesis of several viral diseases and in adenovirus-based vaccination and gene transfer technologies, and may function as markers of severe progression. Inhibition of SR could reduce adenoviral uptake and improve gene therapy and vaccination, as well as reduce pathogenesis. In this review, we will examine the crucial role of SR play in cell entry of different types of human virus, which will allow us to further understand their role in protection and pathogenesis and its potential as antiviral molecules. The recent discovery of SR-B1 as co-factor of SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2) entry is also discussed. Further fundamental research is essential to understand molecular interactions in the dynamic virus-host cell interplay through SR for rational design of therapeutic strategies.
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COVID-19 , Viroses , Vírus , Humanos , Receptores Depuradores/genética , Receptores Depuradores/metabolismo , SARS-CoV-2 , Vírus/genéticaRESUMO
Content available: Author Interview and Audio Recording.
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COVID-19/epidemiologia , SARS-CoV-2 , Viroses/epidemiologia , COVID-19/virologia , Humanos , PandemiasRESUMO
Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause most of the global burden of viral hepatitis. Geographical and seasonal patterns contribute to the epidemiological status of infectious diseases. The extent of these features in the setting of HAV and HEV infections has not been analyzed in detail. This point is important in highly endemic countries of both viruses, where the pediatric population is at high risk of contracting these infections. A comparison between the frequency of antibodies to HAV and HEV and viral RNA detection in serum samples from pediatric patients with acute hepatitis from South and West Mexico was performed. All samples were positive for HAV mono-infection, which was most frequently detected in the metropolitan areas during the rainy season in the South (90%) and all year round in the West (42%). No HEV mono-infection was detected in the studied regions. A 58% frequency for HAV/HEV co-infection was found in the West, predominantly in the metropolitan areas during the rainy months. A 10% frequency for co-infection broadly distributed in the South throughout the year was also found. Our findings underscore that the distribution of HAV and HEV infections varies through the year and differs among Mexico's distinct geographical regions.
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Vírus da Hepatite A , Hepatite A , Vírus da Hepatite E , Hepatite E , Criança , Hepatite A/epidemiologia , Anticorpos Anti-Hepatite , Hepatite E/epidemiologia , Vírus da Hepatite E/genética , Humanos , México/epidemiologiaRESUMO
BACKGROUND: Covid-19 in Mexico is on the rise in different parts of the country. We aimed to study the symptoms and comorbidities that associate with this pandemic in 3 different regions of Mexico. METHODS: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of Mexico (n = 1607) including Northwest Mexico (Sinaloa state), Southeast Mexico (Veracruz state) and West Mexico (Jalisco state) between March 1 and July 30, 2020. Mexico consists of a total population that exceeds 128 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and mortality were performed. RESULTS: A total of 1607 hospitalized patients positive for COVID-19 across all 3 regions of Mexico were included. The average age was 54.6 years and 60.4% were male. A mortality rate of 33.1% was observed. The most common comorbidities were hypertension (43.2%), obesity (30.3%) and diabetes (31.4%). Hypertension was more frequent in West (45%), followed by Northwest (37%) and Southeast Mexico (29%). Obesity was around 30% in Northwest and West whereas an 18% was reported in Southeast. Diabetes was most common in West (34%) followed by Northwest (22%) and Southeast (13%). This might be related to the highest mortality rate in Northwest (31%) and West (37%) when compared to Southeast. Most common symptoms in our overall cohort were fever (80.8%), cough (79.8%), headache (66%), dyspnea (71.1%), myalgia (53.8%), joints pain (50.8%) and odynophagia (34.8%). Diarrhea was the main gastrointestinal (GI) symptom (21.3%), followed by abdominal pain (18%), and nausea/ vomiting (4.5%). Diarrhea and abdominal pain were more common in West (23.1 and 21%), followed by Southeast (17.8, and 9.8%) and Northwest (11.4 and 3.1%). CONCLUSION: Our study showed a high mortality rate likely related to high frequencies of comorbidities (hypertension, obesity and diabetes). Mortality was different across regions. These discrepancies might be related to the differences in the frequencies of comorbidities, and partially attributed to differences in socio-economic conditions and quality of care. Thus, our findings stress the need for improved strategies to get better outcomes in our population.
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COVID-19 , Gastroenteropatias , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Comorbidade , Diabetes Mellitus , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/virologia , Humanos , Hipertensão , Masculino , México , Pessoa de Meia-Idade , Obesidade , SARS-CoV-2RESUMO
We aimed to characterize the contribution of hepatitis E virus (HEV) in perpetuating the cytokine-mediated inflammatory setting related to liver damage in the context of obesity. Herein, serum samples from patients with liver disease were retrospectively analyzed and categorized as normal-weight patients (NW), overweight patients (OW), obese patients (ObP), and high alcohol consumer patients (HAC), and biochemical, anthropometrical, and transient elastography measurements were obtained. The positivity for immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-HEV antibodies in samples was determined by enzyme-linked immunosorbent assay. Available samples from ObP were tested by reverse transcription-nested polymerase chain reaction for the presence of HEV-RNA. Cytokine profile in the serum of ObP was identified using a multiplexed immune assay. Globally, the highest frequency of IgG anti-HEV was found in ObP (57.5%), followed by HAC (20%), OW (15%), and NW (7.5%). A strong association between HEV serology and obesity was found (odds ratio = 4.21, confidence interval = 1.91.9.27) with a cutoff of 29.3 kg/m2 (area under curve [AUC] = 0-66; p = 0.003) and, a 23.7% of available samples of ObP provided amplification of HEV genome. Cytokine analysis revealed significantly higher levels of proinflammatory cytokines (interleukin [IL]-12, interferon [IFN]-γ, and IL-1ß) in IgG anti-HEV-positive ObP than in IgG anti-HEV-negative ObP. Moreover, a high proportion of patients with positive serology showed advanced liver damage. In conclusion, the high percentage of anti-HEV antibodies and viral RNA detection in the setting of an excess of fat, along with an associated proinflammatory cytokine profile found in IgG anti-HEV-positive ObP with more severe liver disease, support an interplay between HEV and obesity.
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Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/imunologia , Obesidade/imunologia , Adulto , Citocinas/sangue , Doença Hepática Terminal/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Despite liver injury in patients infected with severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is associated with prolonged hospitalization, and liver dysfunction is mainly described in patients with severe viral disease. How liver abnormalities may affect virus infection is still unknown. Improved understanding of host genetics, lifestyle, underlying comorbidities and adequate follow-up of patients with liver damage are critical in the new scenario of the pandemic virus.
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Betacoronavirus , Infecções por Coronavirus/complicações , Hepatopatias/virologia , Pandemias , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Humanos , Hepatopatias/diagnóstico , Hepatopatias/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
The post antiretroviral therapy (ART) era for human immunodeficiency virus (HIV) infection resulted in a dramatically increased proportion of deaths attributed to liver-related causes in patients with HIV treated with ART. Additionally, as patients become older as a result of effective ART, liver-related conditions and application of safe therapies are now major concerns in the setting of HIV infection.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Coinfecção , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Hepatopatias/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Human immunodeficiency virus (HIV) predisposes for liver damage during coinfection with hepatitis E virus (HEV) and increases the replication of hepatitis C virus (HCV). HIV-hepatitis B virus (HBV) coinfections are common. In Mexico, hepatotropic viruses are major causative agents of liver disease. However, information on HIV coinfections is limited in the country.
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Coinfecção , Infecções por HIV/virologia , Hepatite B/virologia , Hepatite C/virologia , Hepatite E/virologia , Fígado/virologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Interações Hospedeiro-Patógeno , Humanos , México/epidemiologia , Prognóstico , Fatores de RiscoRESUMO
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis worldwide. The virus is mainly transmitted via the fecaloral route and, the incidence of infection is closely related to low socioeconomic conditions and poor sanitation. Mexico, previously categorized an area of high endemicity for HAV infection, is undergoing epidemiological transition. However, a limited number of HAV-related scientific reports regarding to virus burden is available. According to the local government health agency (Secretarla de Salud, SSA in Spanish), from 1994 to 2017 a reduction in the incidence of hepatitis related to HAV has been reported. However, HAV is still the most common cause of viral hepatitis in the country, and the pediatric population is the most prone to be infected with this virus. The analysis of the SSA data reveals that most of the reported cases from 1994 to 2017 were found in highly industrialized states. This information contradicts the documented relationship between the highest prevalence of infection and the lowest socio-economic status, and supports the necessity of viral detection and notification of HAV cases. Moreover, in spite that four HAV vaccines are available in Mexico and universal vaccination has been shown to be beneficial in developing countries in terms of declining endemicity, HAV vaccination is not mandatory in Mexico. In this review, preventive strategies including appropriate diagnosis, vaccination and public health policies on the basis of the epidemiologic status of HAV in Mexico are discussed.
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Anticorpos Anti-Hepatite A/imunologia , Vacinas contra Hepatite A/uso terapêutico , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Vacinação/métodos , Hepatite A/terapia , Humanos , Incidência , México/epidemiologia , Prevalência , Estudos SoroepidemiológicosRESUMO
INTRODUCTION AND OBJECTIVES: To characterize the virological features of hepatitis E virus (HEV) in serum from patients exhibiting chronic liver damage. METHODS: A data-base of 513 unrelated individuals from West-Mexico with liver-disease determined by clinical and biochemical tests and transient elastography between 2011 and 2016 were retrospectively analyzed. According to infectious etiologies, patients were classified as hepatitis B virus (HBV)-, hepatitis C virus (HCV)-infected patients, and patients exhibiting chronic liver damage with non-identified infectious etiological agent (NIIEA). Available serum samples from NIIEA-patients were tested by RT-nPCR for the presence of HEV-RNA and partially sequenced for genotyping. RESULTS: Out of the 513 cases, 5.85% were patients infected with HBV, 67.64% with HCV, and 26.51% were NIIEA-patients. Among 76 available samples from NIIEA-cases, 30.26% tested positive for HEV-RNA. Twelve (15.79%) partial HEV sequences allowed phylogenetic analysis, revealing the classification of HEV as HEV-Gt3. Advanced fibrosis (F3-F4 stage) was found in a 26.1% of patients with HEV-active infection. CONCLUSION: Although HCV is the main infectious agent related to chronic liver disease in Mexico, liver damage without an infectious etiology is common. Our findings reveal that an elevated rate of chronic liver disease might be represented by autochthonous infection of HEV-Gt3, whose detection makes Mexico unique in Latin-America with the circulation of HEV strains belonging to three genotypes (Gt1, Gt2, and Gt3). Thus, HEV infection should be a matter of health concern, and mandates for HEV screening to properly handle this commonly undiagnosed disease.
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Vírus da Hepatite E/genética , Hepatite E/epidemiologia , Cirrose Hepática/virologia , RNA Viral/sangue , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Doença Crônica , Técnicas de Imagem por Elasticidade , Feminino , Genótipo , Hepatite E/sangue , Hepatite E/diagnóstico , Hepatite E/virologia , Humanos , L-Lactato Desidrogenase/sangue , Cirrose Hepática/sangue , Hepatopatias/sangue , Hepatopatias/virologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Contagem de Plaquetas , Reação em Cadeia da Polimerase , RNA Viral/análise , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVE: We aimed to detect and characterize hepatitis E virus (HEV) RNA in sera samples from a pediatric population infected with the hepatitis A virus (HAV) exhibiting acute hepatitis and to correlate the infection status with the clinical outcome. METHODS: Seventy-five ELISA-positive samples from children containing anti-HAV and anti-HEV IgM were used to amplify and characterize partial regions within HEV ORF2. A statistical comparison of clinical data between HEV IgM-positive/HEV RNA-positive patients and HEV IgM-positive/HEV RNA-negative patients was performed. RESULTS: Thirteen out of 75 IgM-positive samples provided amplification of discrete regions of the HEV genome. Nested RT-PCR-based detection and subsequent sequencing of 5 samples confirmed the identity of HEV genotype 1 (G1), which had not been previously reported in Mexico. Though not significant, a trend towards exacerbated clinical manifestations was found in HEV RNA-positive patients relative to HEV RNA-negative patients. CONCLUSIONS: An elevated rate of G1 RNA was detected. Hepatitis E seems to be a neglected disease in Mexico and epidemic strains of HEV are likely to play a role as causative agents of acute hepatitis in highly exposed children. Although HAV is endemic in Mexico, an HEV-RNA detection rate of 17% in co-infected samples shows the need for screening for HEV as a part of future vaccination strategies.