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

https://doi.org/10.1016/j.jcv.2011.06.015Get rights and content

Abstract

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.

Section snippets

Background

Hepatitis E virus (HEV) is the only member of the genus Hepevirus in the family Hepeviridae.1 In low endemic regions, imported and autochthonous sporadic hepatitis E cases have been reported, and the close genetic relationship between swine and human variants strongly suggests their zoonotic spread.2, 3, 4, 5

Although seroprevalence of antibodies to HEV (anti-HEV) has been determined in different population groups in Latin America, and although IgM anti-HEV in acute hepatitis has been found in

Objective

This study was conducted to serologically diagnose and molecularly characterize new cases of hepatitis E in patients in Argentina.

Study population

Samples (sera and feces) from 76 adults (52% female, median age: 40 years; range: 18–74) and 155 children (55% female, median age: 7.3 years) with acute non-A-C hepatitis, referred from hospitals located both in Buenos Aires and environs and in certain Argentine provinces, were studied at the National Reference Laboratory for viral hepatitis from January 2005 to December 2010.

Additional samples from 15 children with fulminant liver failure (FHF) and hepatitis A (8 female, median age: 7.5 years)

Results

During the six-year period studied, fifteen patients (13 adults and 2 children) were diagnosed with acute hepatitis E. Seven required hospitalization due to its severity. Additional information on patients is summarized in Table 1; where patients acquired the infection is indicated in Fig. 1.

Nine cases were nested RT-PCR HEV RNA-positive for the ORF 2 region. In five of them, an ORF1 fragment was also sequenced. The lower sensitivity for ORF 1 has been previously reported.18, 19

The genotype and

Discussion

The above results show that HEV has continued circulating in Argentina during the last six years. The different subgenotypes and polyphyletic variants found suggest multiple sources of infection.

Subgenotype 3i, the first described in humans and swine in Argentina, is still circulating. In this study, we found this subgenotype not only in Buenos Aires, but also in the province of Mendoza (center-west). The precedent of having traveled abroad would support the assumption of an imported case when

Conflict of interest statement

None.

Acknowledgments

We thank to Drs Fainboin, Schroder, Paz and Estepo from Hospital Muñiz, Drs Ciocca and Cuarterolo from Hospital Garrahan, Drs Alessio and Frider from Hospital Argerich, Drs Bonacci and Gadano from Hospital Italiano, Drs Gruz and Descalzi from Fundación Favaloro, Drs Martínez and Poncino from Sanatorio Méndez, and Drs Espul and Vicente from Mendoza.

Special thanks are given to the “Red Iberoamericana para la Investigación de la Hepatitis E (RIHEPE)” and to Dr José Manuel Echevarría.

References (29)

  • M. Fogeda et al.

    Imported and autochthonous hepatitis E virus strains in Spain

    J Med Virol

    (2009)
  • L. Rodríguez Lay et al.

    Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998–2003

    J Med Virol

    (2008)
  • L. Villalba Mde et al.

    Hepatitis E virus genotype 1, Cuba

    Emerg Infect Dis

    (2008)
  • G.G. Schlauder et al.

    Identification of 2 novel isolates of hepatitis E virus in Argentina

    J Infect Dis

    (2000)
  • Cited by (19)

    • Serologic evidence of the circulation of the hepatitis E virus and the prevalence of antibodies against hepatitis A in an indigenous population in northern Argentina

      2021, Revista Argentina de Microbiologia
      Citation Excerpt :

      Otherwise, the presumptive diagnosis of such patients is idiopathic hepatotoxicity. Detection of HEV RNA in 15.8% of patients with acute non-A non-B hepatitis evidenced circulation of the virus in central Argentina36 (Table 1). Further, the virus was detected in rivers and sewage samples in 2013 in the central region of Argentina during an environmental surveillance study32.

    • Acute hepatitis E virus infection and association with a subacute thyroiditis

      2015, Annals of Hepatology
      Citation Excerpt :

      Both of them showed a homology of 92 to 94% with human and swine 3a variants from Japan. The homology with other human HEV 3a variants characterized in Argentina varied between 72 and 85%.8 The patient had spontaneous improvement with a gradual decrease in the symptoms.

    • First detection of hepatitis E virus in Central Argentina: Environmental and serological survey

      2014, Journal of Clinical Virology
      Citation Excerpt :

      Even though ORF-2 region has been extensively studied to infer phylogenetic relationships among HEV genotypes and subtypes [30–32], phylodynamic and coalescent studies among this region has been recently reported [12,29,33,34]. Detection of subtypes 3a and 3b agrees with subtypes previously detected in clinical samples from Argentinean patients [10]. Subtype 3c had not been previously described in our region.

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

      2014, Annals of Hepatology
      Citation Excerpt :

      This is in agreement with those previously characterized in Buenos Aires province in 2002.11 Swine subgenotypes 3a or 3b HEV variants that relate to the human ones that have been found in Argentina since 2004 have not yet been detected.8 Many studies have demonstrated HEV RNA in the pork chain food, seafood and crops.1,2,24,26

    View all citing articles on Scopus
    View full text