We describe a clinical case of a kidney transplant patient whopresented a sudden elevation of his liver function tests. Oncewe ruled out the most frequent causes of acute hepatitis, serumtests for Hepatitis E were performed. Hepatitis E virusRNA was detected in blood and stools. After six months thevirus was still detected. Ribavirin treatment was initiatedwith normalization of the serum aminotransferases and sustainedvirology response was achieved.

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.

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.

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.

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.

Background Hepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds. An autochthonous human case of acute hepatitis E was recently reported. To obtain a better understanding of the phenotypic profiles of both human and swine HEV strains, a experimental study was conducted using the animal model, Macaca fascicularis . Methods Six cynomolgus monkeys ( Macaca fascicularis ) were inoculated intravenously with swine HEV genotype 3 that was isolated from naturally and experimentally infected pigs in Brazil and the Netherlands. Two other monkeys were inoculated with HEV genotype 3 that was recovered from Brazilian and Argentinean patients with locally acquired acute and fulminant hepatitis E. The haematological, biochemical, and virological parameters of all animals were monitored for 67 days. Results Subclinical hepatitis was observed in all monkeys after inoculation with HEV genotype 3 that was recovered from the infected swine and human patients. HEV RNA was detected in the serum and/or faeces of 6 out of the 8 cynomolgus monkeys between 5 and 53 days after inoculation. The mild inflammation of liver tissues and elevations of discrete liver enzymes were observed. Seroconversions to anti-HEV IgM and/or IgG were detected in 7 animals. Reactivities to anti-HEV IgA were also detected in the salivary samples of 3 animals. Interestingly, all of the infected monkeys showed severe lymphopenia and a trend toward monocytosis, which coincided with elevations in alanine aminotransferase and antibody titres. Conclusions The ability of HEV to cross the species barrier was confirmed for both the swine (Brazilian and Dutch) and human (Argentinean) strains, thus reinforcing the zoonotic risk of hepatitis E in South America. Cynomolgus monkeys that were infected with HEV genotype 3 developed subclinical hepatitis that was associated with haematological changes. Haematological approaches should be considered in future studies of HEV infection.

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

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. (C) 2011 Elsevier B. V. All rights reserved.

OBJECTIVES:To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005.DESIGN:Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid.SETTING:Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina.PATIENTS:Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid.CONCLUSIONS:Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.

BACKGROUND:Hepatitis A infection, a vaccine-preventable disease, is an important cause of fulminant hepatic failure (FHF) in children in Argentina. Universal vaccination in 1-year-old children was implemented in June 2005. The limited studies about the correlation between the characteristics of the hepatitis A virus (HAV) and FHF have been carried out in adults.METHODS:Samples from 41 children with FHF were studied from September 2003 to January 2006 and HAV RNA was detected, sequenced and analysed in the 5' non-coding region and VP1/2A region.RESULTS:Eighteen HAV strains were characterized and found to be different at the nucleotide level from the self-limited acute infection strains that have been circulating in Argentina with no temporal or geographical pattern. They did not form a genetic cluster, but some of them were identical in the largest fragment characterized and some of them seemed to be more closely related in time and/or geographically.CONCLUSION:Our results suggest that viral factors could be involved in the severity of the clinical presentation of HAV infection in children in Argentina.

Hepatitis A, a vaccine preventable disease, is now of transitional or intermediate endemicity in Argentina, as the epidemiologic pattern of the disease has shifted with improvements in living conditions in some parts of the country. Increase in the susceptibility of older children and adults has led to increasing disease incidence. Molecular epidemiology has played an important role in the understanding of HAV infection by identifying modes of spreading and by permitting the monitoring of changes in circulating virus brought about by prevention programs. South American isolates characterized are limited. Eighty-two sporadic and outbreak isolates from Argentina were sequenced in the VP1/2A region of HAV genome over a 9-year period. All the isolates belonged to subgenotype IA. All our sequences grouped into two big clusters. Apparently, at least two lineages have been co-circulating in the same place at the same time. Despite great genetic variability, few point amino acid changes could be deduced. Four sequences showed an Arg --> Lys substitution at 1-297 which characterized the genotype IB at the amino acid level. Many isolates carried a conservative amino acid substitution Leu --> Ile at position 42 of the 2A domain, previously described as a possible fingerprint of HAV sequences in Brazil. The other rare changes have been found before, except for a 1-277 Asn --> Ser substitution displayed in two isolates that has not been previously reported. Argentina recently implemented universal vaccination in 1-year-old children. Molecular tools would be useful in an active surveillance program.

In Argentina, a country considered non-endemic for hepatitis E virus (HEV) infection, serologic evidence of HEV infection has been observed in different human population groups. In other countries, a high degree of genetic relatedness has been observed between human and swine HEV genotype 3 sequences, suggesting zoonosis as one probable route of infection. This is the first identification of swine HEV in South America. HEV RNA was detected and sequenced in the ORF 1 and ORF 2 regions from swine fecal samples from a herd located in Pergamino, in the province of Buenos Aires. These strains all group into genotype 3 and exhibit a close relationship to two novel HEV variants previously identified in Argentina from sporadic acute cases of non-A to -C hepatitis in humans. In addition, using a modified commercial ELISA, the presence of anti-HEV antibodies was surveyed in five provinces across the country and all five showed a prevalence of HEV antibodies, ranging from 4% to 58%. The results suggest that swine could be an important reservoir for virus transmission in Argentina as has been suggested for other nonendemic areas. The Argentine human strains and swine strain described in this article seem to be closely related to a human Austrian strain, suggesting a potential European origin of HEV infection in these cases.

Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liver failure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentina and it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologic surveillance may contribute to efficient control and lead to rational decisions in public health policies.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples fJom 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys fom Buenos Aires province and the third was a 3-year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains fJom sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEVin children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALE Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV presently in phase III trials.