[Hepatitis E virus-associated aplastic anemia. Report of a case]. / Anemia aplásica asociada a hepatitis E. Informe de un caso.

Hepatitis-associated aplastic anemia (HAAA) is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis; it can be observed in up to 5% in the aplastic anemia in West Europe and North American countries and 10% in the East Asia. Although hepatotropic and other viruses were suspected of causing HAAA, this hypothesis was rarely confirmed. Currently, the infection with hepatitis E virus represents the first cause of acute hepatitis in the world. Its genotype 3, the most frequent in Argentina and other Latin American countries, was associated with extrahepatic complications (renal, pancreatic, neurologic and hematologic). To our knowledge, only one case of hepatitis E virus-associated aplastic anemia has been previously reported, in Pakistan; the case presented here would be the first in Argentina. The patient was treated with thymoglobulin, cyclosporine, corticosteroids, filgastrim and transfusional support. She developed fungemia due to Candida tropicalis that remitted with equinocandins and therefore fever, pulmonary infiltrates and a solitary nodular cerebral image with serum galactomannan (DO index > 1.0 ng/ml) that resolved with voriconazol. She was discharged three months after her admission without transfusion requirements and normal hepatic values.With this in mind, it would be advisable to investigate hepatitis E (HEV) as a cause of HAAA in Argentina.

[Hepatitis C patients' record in the Sentinel Units for viral Hepatitis in Argentina 2007- 2014. Distribution by year of birth]. / Registro de pacientes con hepatitis C en las Unidades Centinela para hepatitis virales en Argentina, 2007 - 2014. Distribución por año de nacimiento.

Recommendations for Hepatitis C screening based on risk factorsfor transmission proved to be ineffcient. Accordingly, the CDC recommended to screen all American individuals born between 1945-1965, based on data from population prevalence of infection. The effectiveness of implementing these recommendations in other contexts and/or populations can be estimated, in principle, knowing the age distribution of infected individuals. There is no data on population prevalence in our country. Yet we can know the age distribution of cases of Hepatitis C who accessed the health system. The aim of this paper is to analyze the distribution by birth cohort ofcases registered as "Hepatitis C" in the Sentinel Units for Viral Hepatitis in the 2007-2014 period. This will contribute to the identification, if any, ofa cohort in which case the recommendation of screening could be addressed, based on risk factors inherent to our country and our epidemiological reality. The age distribution of our cases was wider and younger than those of the population supporting the recommendation of the CDC and this suggests -beyond the difference in the populations being compared- is due to a range of risk factors and age at different infection between USA and Argentina. Thus, based on these results, the recommendation of the Argentine Consensus for Hepatitis C in 2013 to screen all individuals once in life is supported.

Molecular surveillance of hepatitis A virus in Argentina: first subgenotype IB detected in a traveler.

By using molecular surveillance of hepatitis A virus, we characterized for the first time a subgenotype IB imported case in Argentina, a country with universal vaccination since 2005. The case was a crew member of a cruise ship. We consider this a case alert because of its multiple implications.

Updating the knowledge of hepatitis E: new variants and higher prevalence of anti-HEV in Argentina.

INTRODUCTION: Hepatitis E is a disease of global distribution, with significant morbidity and mortality, whose scope and burden continue to emerge in low endemic countries. MATERIAL AND METHODS: In 2012, we studied the prevalence of anti-HEV antibodies in 202 adult serum samples. We also analyzed samples from 143 patients with acute non-A-C hepatitis from January 2011 to December 2013. Acute HEV infections were diagnosed with anti-HEV IgM and/or HEV RNA. HEV RNA was also investigated in 94 swine fecal samples. HEV RNA was sequenced and characterized. RESULTS: We found higher values of prevalence than those previously reported in the 1990s. The overall prevalence of anti-HEV IgG antibodies was 15.4%. The prevalence was 10.6% in the 123 adults voluntarily screened on World Hepatitis Day 2012 in Buenos Aires city and 14.8, 16.7 and 35.7% respectively in the smaller groups of healthcare workers, blood donors and HIV-positive patients from different regions of the country. Nine acute HEV infections were diagnosed in the three years analyzed. We characterized new human variants of subgenotype 3a and 3i. New subgenotype 3i variants were found in swine from two distant provinces closely related to the human ones. CONCLUSIONS: These results enlarge the knowledge of HEV and contribute with new information. However, higher values of prevalence found in small groups need to be confirmed in larger studies. Many aspects of the spectrum of the disease and the reservoirs and routes of transmission are still unknown and thus deserve additional research.

[Surveillance of viral hepatitis in Argentina: analysis of information from sentinel units 2007-2010]. / Vigilancia de hepatitis virales en Argentina: análisis de información obtenida por las Unidades Centinela 2007-2010.

In Argentina, the four strategies of epidemiological surveillance from the National System of Health Surveillance (SNVS) are Diseases of Mandatory Report (C2), Sentinel Units (SU), Laboratory Surveillance (SIVILA) and National Programs (National Plan of Blood, information from blood banks). They collect information about viral hepatitis (VH). The objective of this work was to analyze the information recorded by the SUs of VH for hepatitis B and C in the period between January 1th 2007 and December 31h 2010. In this period, out of the 1,769 cases recorded (entered by 21 of 24 SUs), 806 entries were hepatitis B, 848 hepatitis C and 115 belonged to other definitions. The relative proportions between hepatitis B and hepatitis C were heterogeneous between the SUs. The age distribution was homogeneous, being the predominant group in acute hepatitis B the 25- to 34-year-old group. In hepatitis C, the age distribution was broader. The distribution by sex and risk factors was heterogeneous between the different SUs. In hepatitis C, genotype 1 was the predominant one. In conclusion, the information provided by the SUs contributes as an evidence of the public health problem posed by this pathology in our country.

High prevalence of hepatitis A and E viruses in environmental and clinical samples from West Argentina.

Environmental surveillance of water sources is important to monitoring viral hepatitis transmission in clinical settings. This study investigated the circulation of hepatitis A (HAV) and E (HEV) viruses in sewage and clinical samples from Argentina. Between 2016 and 2017, 80 raw sewage samples and 86 clinical samples (stool and serum) from suspected cases of hepatitis A and hepatitis E were obtained. HAV and HEV were tested by both real-time and nested PCR. Positive samples were sequenced for genotype determination and phylogenetic analysis. Overall, HAV was recovered in 39% of sewage samples and 61.1% of clinical samples. HEV was detected in 22.5% of sewage samples and 15.9% of clinical samples. HAV was found more frequently in sewage during the winter and in clinical samples in spring; HEV was more prevalent in sewage during summer and in clinical samples in autumn. All HAV isolates belonged to genotype IA and HEV isolates belonged to genotype 3, the most prevalent genotypes in South America. High prevalence of HAV and HEV in environmental and clinical samples in Mendoza, Argentina was observed. These findings reinforce the importance of environmental surveillance and implementation of health strategies to control the spread of HAV and HEV in developing countries.

Phylogeography and evolutionary history of hepatitis E virus genotype 3 in Argentina.

BACKGROUND: Few studies about the evolutionary history of the hepatitis E virus (HEV) have been conducted. The aim of our work was to investigate and make inferences about the origin and routes of dispersion of HEV-3 in Argentina. METHODS: Phylogenetic, coalescent and phylogeographic analyses were performed using a 322-bp ORF2 genomic fragment of all HEV-3 sequences with known date and place of isolation published at GenBank until May 2018 (n=926), including 16 Argentinian sequences (isolated from pigs, water and humans). RESULTS: Phylogenetic analysis revealed two clades within HEV-3: abchij and efg. All Argentinian samples were grouped intermingled within clade 3abchij. The coalescent analysis showed that the most recent common ancestor for the clade 3abchij would have existed around the year 1967 (95% highest posterior density (HPD): 1963-1970). The estimated substitution rate was 1.01×10-2 (95%HPD: 9.3×10-3-1.09×10-2) substitutions/site/y, comparable with the rate previously described. The phylogeographic approach revealed a correspondence between phylogeny and place of origin for Argentinian samples, suggesting many HEV introductions in the country, probably from Europe and Japan. CONCLUSIONS: This is the first evolutionary inference of HEV-3 that includes Argentinian strains, showing the circulation of many HEV-3 subtypes, obtained from different sources and places, with recent diversification processes. ACCESSION NUMBERS: [KX812460], [KX812461], [KX812462], [KX812465], [KX812466], [KX812467], [KX812468], [KX812469].

High prevalence of hepatitis A and E viruses in environmental and clinical samples from West Argentina

ABSTRACT Environmental surveillance of water sources is important to monitoring viral hepatitis transmission in clinical settings. This study investigated the circulation of hepatitis A (HAV) and E (HEV) viruses in sewage and clinical samples from Argentina. Between 2016 and 2017, 80 raw sewage samples and 86 clinical samples (stool and serum) from suspected cases of hepatitis A and hepatitis E were obtained. HAV and HEV were tested by both real-time and nested PCR. Positive samples were sequenced for genotype determination and phylogenetic analysis. Overall, HAV was recovered in 39% of sewage samples and 61.1% of clinical samples. HEV was detected in 22.5% of sewage samples and 15.9% of clinical samples. HAV was found more frequently in sewage during the winter and in clinical samples in spring; HEV was more prevalent in sewage during summer and in clinical samples in autumn. All HAV isolates belonged to genotype IA and HEV isolates belonged to genotype 3, the most prevalent genotypes in South America. High prevalence of HAV and HEV in environmental and clinical samples in Mendoza, Argentina was observed. These findings reinforce the importance of environmental surveillance and implementation of health strategies to control the spread of HAV and HEV in developing countries.

Identifications of polyphyletic variants in acute hepatitis suggest an underdiagnosed circulation of hepatitis E virus in Argentina.

BACKGROUND: In recent years, an increasing number of infections with genotype 3 hepatitis E virus (HEV) have been reported in western countries. Data in South America, however, are still scarce. Swine and human variants previously described in Argentina are closely related to a human Austrian one. OBJECTIVE: To identify whether HEV is still circulating in Argentina. STUDY DESIGN: Sera and stool samples from adults and children with unexplained acute liver disease referred to our center during the last six years were prospectively studied. Dual infection with hepatitis A was retrospectively studied in a group of children with fulminant hepatic failure. RESULTS: Fifteen new cases (13 adults and 2 children), seven of whom required hospitalization, were diagnosed. Nine had detectable HEV RNA, and one had imported genotype 1. Subgenotype 3i HEV-related variants are still circulating. Five autochthonous sequences, related to European, American and Japanese ones, grouped in subgenotype 3a. One case had a subgenotype 3b variant. DISCUSSION: The polyphyletic variants widespread in Argentina suggest multiple sources of infection. Whether or not their reservoir is swine merits further investigation. Since hepatitis E is still considered rare, differential laboratory testing in unexplained acute liver disease is not routinely performed in Argentina. Broadening awareness of this disease is important in light of the decrease in hepatitis A incidence since universal vaccination was implemented in 2005. The diagnosis of hepatitis E with a combination of serological and molecular tools is needed to better understand its epidemiology and impact on the clinical management of patients with unexplained increased transaminases.

Anemia aplásica asociada a hepatitis E: Informe de un caso

La aplasia medular asociada a hepatitis (HAAA) es una reconocida entidad clínica donde la falla medular es precedida de una hepatitis; se observa hasta en el 5% de las aplasias en Europa occidental y América del Norte y hasta en el 10% de ellas en el Este asiático. Se ha sospechado de los virus hepatotropos y otros virus como responsables de HAAA, pero esta asociación raramente se ha confirmado. La hepatitis por virus E es la causa más frecuente de hepatitis viral en el mundo. Su genotipo 3, de mayor circulación en la Argentina y otros países de Latinoamérica, puede presentar complicaciones extrahepáticas (renales, neurológicas, pancreáticas y hematológicas). Hasta aquí, en nuestro conocimiento solo se ha publicado un caso de HAAA por virus de la hepatitis E en Pakistán; el que ahora presentamos sería el primero comunicado en la Argentina. La paciente fue tratada con timoglobulina, ciclosporina, corticosteroides, filgastrim y soporte transfusional. Desarrolló fungemia por Candida tropicalis que respondió a equinocandinas, y luego infiltrados pulmonares e imagen nodular cerebral con galactomananos en suero (índice DO > 1.0 ng/ml) que resolvieron con voriconazol. Fue dada de alta independiente de transfusiones, tres meses después de su admisión, con hepatograma normal. Teniendo en cuenta este caso, sería conveniente investigar la hepatitis E como causa de HAAA en la Argentina.

Hepatitis-associated aplastic anemia (HAAA) is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis; it can be observed in up to 5% in the aplastic anemia in West Europe and North American countries and 10% in the East Asia. Although hepatotropic and other viruses were suspected of causing HAAA, this hypothesis was rarely confirmed. Currently, the infection with hepatitis E virus represents the first cause of acute hepatitis in the world. Its genotype 3, the most frequent in Argentina and other Latin American countries, was associated with extrahepatic complications (renal, pancreatic, neurologic and hematologic). To our knowledge, only one case of hepatitis E virus-associated aplastic anemia has been previously reported, in Pakistan; the case presented here would be the first in Argentina. The patient was treated with thymoglobulin, cyclosporine, corticosteroids, filgastrim and transfusional support. She developed fungemia due to Candida tropicalis that remitted with equinocandins and therefore fever, pulmonary infiltrates and a solitary nodular cerebral image with serum galactomannan (DO index > 1.0 ng/ml) that resolved with voriconazol. She was discharged three months after her admission without transfusion requirements and normal hepatic values.With this in mind, it would be advisable to investigate hepatitis E (HEV) as a cause of HAAA in Argentina.

Vigilancia de hepatitis virales en Argentina: análisis de información obtenida por las Unidades Centinela 2007-2010 / [Surveillance of viral hepatitis in Argentina: analysis of information from sentinel units 2007-2010].

In Argentina, the four strategies of epidemiological surveillance from the National System of Health Surveillance (SNVS) are Diseases of Mandatory Report (C2), Sentinel Units (SU), Laboratory Surveillance (SIVILA) and National Programs (National Plan of Blood, information from blood banks). They collect information about viral hepatitis (VH). The objective of this work was to analyze the information recorded by the SUs of VH for hepatitis B and C in the period between January 1th 2007 and December 31h 2010. In this period, out of the 1,769 cases recorded (entered by 21 of 24 SUs), 806 entries were hepatitis B, 848 hepatitis C and 115 belonged to other definitions. The relative proportions between hepatitis B and hepatitis C were heterogeneous between the SUs. The age distribution was homogeneous, being the predominant group in acute hepatitis B the 25- to 34-year-old group. In hepatitis C, the age distribution was broader. The distribution by sex and risk factors was heterogeneous between the different SUs. In hepatitis C, genotype 1 was the predominant one. In conclusion, the information provided by the SUs contributes as an evidence of the public health problem posed by this pathology in our country.