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Archives of Virology

, Volume 163, Issue 1, pp 43–49 | Cite as

Serological and molecular markers of hepatitis E virus infection in HIV-infected patients in Brazil

  • A. C. Ferreira
  • Michele Soares Gomes-Gouvêa
  • G. Lisboa-Neto
  • M. C. J. Mendes-Correa
  • C. M. Picone
  • N. A. Salles
  • A. Mendrone-Junior
  • F. J. Carrilho
  • J. R. R. Pinho
Original Article

Abstract

In Brazil, the circulation of hepatitis E virus (HEV) has been demonstrated in distinct groups of individuals and some animals, but its prevalence among individuals with human immunodeficiency virus (HIV) infection is unknown. This study aimed to assess the frequency of serological and molecular HEV markers in individuals infected with HIV from São Paulo, Brazil. Serum and plasma samples of 354 HIV-infected patients collected between 2007 and 2013 were included. All samples were tested for anti-HEV IgG and IgM antibodies and HEV RNA. Anti-HEV IgG and IgM antibodies were detected in 10.7% (38/354) and 1.4% (5/354) of the samples, respectively. Both antibodies were detected simultaneously in only two samples. HEV RNA was not detected in any sample. There was no significant correlation of anti-HEV serological status (positivity to anti-HEV IgG and/or IgM) with sex, age, CD4+ T cell count, HIV viral load, antiretroviral therapy, liver enzyme levels, or coinfection with hepatitis B virus and/or hepatitis C virus. Our study provides serological evidence of past and recent HEV infections in HIV-infected patients from São Paulo, Brazil. However, the occurrence of ongoing HEV infection appears be a rare event in this population.

Notes

Acknowledgements

We would like to thank all patients who participated in the study.

Compliance with ethical standards

Funding

This study was supported by grant 2012/50504-2 from the São Paulo Research Foundation (FAPESP) and Alves de Queiroz Family Fund for Research. Ariana Carolina Ferreira is a graduate student from the Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil, and received a fellowship from FAPESP (2012/21588-3) and CAPES. João Renato Rebello Pinho and Maria Cássia Mendes Correa received a fellowship from CNPq (Bolsista de Produtividade em Pesquisa do CNPq - Nível 2).

Conflict of interest

João Renato Rebello Pinho is an employee of Albert Einstein Medicina Diagnóstica, São Paulo, Brazil. All other authors who took part in this study declare that they have no conflicts of interest or disclosures with respect to the manuscript.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

All participants provided written informed consent prior to enrollment in the study.

References

  1. 1.
    Assis SB, Souto FJ, Fontes CJ, Gaspar AM (2002) Prevalence of hepatitis A and E virus infection in school children of an Amazonian municipality in Mato Grosso State. Rev Soc Bras Med Trop 35:155–158CrossRefPubMedGoogle Scholar
  2. 2.
    Balayan MS, Andjaparidze AG, Savinskaya SS, Ketiladze ES, Braginsky DM, Savinov AP, Poleschuk VF (1983) Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 20:23–31CrossRefPubMedGoogle Scholar
  3. 3.
    Balayan MS, Fedorova OE, Mikhailov MI, Rytick PG, Eremin VF, Danilova TI, Shevelev BI, Gorbacheva EC, Pankova GY (1997) Antibody to hepatitis E virus in HIV-infected individuals and AIDS patients. J Viral Hepat 4:279–283CrossRefPubMedGoogle Scholar
  4. 4.
    Bortoliero AL, Bonametti AM, Morimoto HK, Matsuo T, Reiche EM (2006) Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Parana, Brazil. Rev Inst Med Trop Sao Paulo 48:87–92CrossRefPubMedGoogle Scholar
  5. 5.
    Colson P, Kaba M, Moreau J, Brouqui P (2009) Hepatitis E in an HIV-infected patient. J Clin Virol Off Publ Pan Am Soc Clin Virol 45:269–271CrossRefGoogle Scholar
  6. 6.
    Crum-Cianflone NF, Curry J, Drobeniuc J, Weintrob A, Landrum M, Ganesan A, Bradley W, Agan BK, Kamili S, Infectious Disease Clinical Research Program HIVWG (2012) Hepatitis E virus infection in HIV-infected persons. Emerg Infect Dis 18:502–506CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    da Costa Lana MV, Gardinali NR, da Cruz RA, Lopes LL, Silva GS, Caramori Junior JG, de Oliveira AC, de Almeida Souza M, Colodel EM, Alfieri AA, Pescador CA (2014) Evaluation of hepatitis E virus infection between different production systems of pigs in Brazil. Trop Anim Health Prod 46:399–404CrossRefPubMedGoogle Scholar
  8. 8.
    Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S (2009) Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med 361:1025–1027CrossRefPubMedGoogle Scholar
  9. 9.
    Dalton HR, Kamar N, Izopet J (2014) Hepatitis E in developed countries: current status and future perspectives. Future Microbiol 9:1361–1372CrossRefPubMedGoogle Scholar
  10. 10.
    Dalton HR, Webb GW, Norton BC, Woolson KL (2016) Hepatitis E virus: time to change the textbooks. Dig Dis 34:308–316CrossRefPubMedGoogle Scholar
  11. 11.
    de Souza AJ, Gomes-Gouvêa MS, Soares Mdo C, Pinho JR, Malheiros AP, Carneiro LA, dos Santos DR, Pereira WL (2012) HEV infection in swine from Eastern Brazilian Amazon: evidence of co-infection by different subtypes. Comp Immunol Microbiol Infect Dis 35:477–485Google Scholar
  12. 12.
    Debes JD, Martinez Wassaf M, Pisano MB, Isa MB, Lotto M, Marianelli LG, Frassone N, Ballari E, Bohjanen PR, Hansen BE, Re V (2016) Increased hepatitis E virus seroprevalence correlates with lower CD4+ cell counts in HIV-infected persons in Argentina. PLoS One 11:e0160082CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Debes JD, Pisano MB, Lotto M, Re V (2016) Hepatitis E virus infection in the HIV-positive patient. J Clin Virol Off Publ Pan Am Soc Clin Virol 80:102–106CrossRefGoogle Scholar
  14. 14.
    dos Santos DR, Vitral CL, de Paula VS, Marchevsky RS, Lopes JF, Gaspar AM, Saddi TM, Junior NC, Guimaraes Fde R, Junior JG, Ximenes LL, Souto FJ, Pinto MA (2009) Serological and molecular evidence of hepatitis E virus in swine in Brazil. Vet J 182:474–480CrossRefPubMedGoogle Scholar
  15. 15.
    Fainboim H, Gonzalez J, Fassio E, Martinez A, Otegui L, Eposto M, Cahn P, Marino R, Landeira G, Suaya G, Gancedo E, Castro R, Brajterman L, Laplume H (1999) Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat 6:53–57CrossRefPubMedGoogle Scholar
  16. 16.
    Feldt T, Sarfo FS, Zoufaly A, Phillips RO, Burchard G, van Lunzen J, Jochum J, Chadwick D, Awasom C, Claussen L, Drosten C, Drexler JF, Eis-Hubinger AM (2013) Hepatitis E virus infections in HIV-infected patients in Ghana and Cameroon. J Clin Virol Off Publ Pan Am Soc Clin Virol 58:18–23CrossRefGoogle Scholar
  17. 17.
    Freitas NR, Santana EB, Silva AM, Silva SM, Teles SA, Gardinali NR, Pinto MA, Martins RM (2016) Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. Mem Inst Oswaldo Cruz 111:692–696CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Geng Y, Zhang H, Huang W, Harrison TJ, Geng K, Li Z, Wang Y (2014) Persistent hepatitis e virus genotype 4 infection in a child with acute lymphoblastic leukemia. Hepat Mon 14:e15618PubMedPubMedCentralGoogle Scholar
  19. 19.
    Gerolami R, Moal V, Colson P (2008) Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N Engl J Med 358:859–860CrossRefPubMedGoogle Scholar
  20. 20.
    Goncales NS, Pinho JR, Moreira RC, Saraceni CP, Spina AM, Stucchi RB, Filho AD, Magna LA, Goncales Junior FL (2000) Hepatitis E virus immunoglobulin G antibodies in different populations in Campinas, Brazil. Clin Diagn Lab Immunol 7:813–816PubMedPubMedCentralGoogle Scholar
  21. 21.
    Guimaraes FR, Saddi TM, Vitral CL, Pinto MA, Gaspar AMC, Souto FJD (2005) Hepatitis E virus antibodies in swine herds of MATO Grosso State, Central Brazil. Braz J Microbiol 36:223–226CrossRefGoogle Scholar
  22. 22.
    Haagsma EB, van den Berg AP, Porte RJ, Benne CA, Vennema H, Reimerink JH, Koopmans MP (2008) Chronic hepatitis E virus infection in liver transplant recipients. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc 14:547–553Google Scholar
  23. 23.
    Hartl J, Otto B, Madden RG, Webb G, Woolson KL, Kriston L, Vettorazzi E, Lohse AW, Dalton HR, Pischke S (2016) Hepatitis E seroprevalence in Europe: a meta-analysis. Viruses 8(8):211Google Scholar
  24. 24.
    Hartl J, Wehmeyer MH, Pischke S (2016) Acute hepatitis E: two sides of the same coin. Viruses 8(11):299Google Scholar
  25. 25.
    Heldt FH, Staggmeier R, Gularte JS, Demoliner M, Henzel A, Spilki FR (2016) Hepatitis E virus in surface water, sediments, and pork products marketed in Southern Brazil. Food Environ Virol 8:200–205CrossRefPubMedGoogle Scholar
  26. 26.
    Hering T, Passos AM, Perez RM, Bilar J, Fragano D, Granato C, Medina-Pestana JO, Ferraz ML (2014) Past and current hepatitis E virus infection in renal transplant patients. J Med Virol 86:948–953CrossRefPubMedGoogle Scholar
  27. 27.
    Ingiliz P, Mayr C, Obermeier M, Herbst H, Polywka S, Pischke S (2016) Persisting hepatitis E virus infection leading to liver cirrhosis despite recovery of the immune system in an HIV-infected patient. Clin Res Hepatol Gastroenterol 40:e23–e25CrossRefPubMedGoogle Scholar
  28. 28.
    Jothikumar N, Cromeans TL, Robertson BH, Meng XJ, Hill VR (2006) A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods 131:65–71CrossRefPubMedGoogle Scholar
  29. 29.
    Kaba M, Richet H, Ravaux I, Moreau J, Poizot-Martin I, Motte A, Nicolino-Brunet C, Dignat-George F, Menard A, Dhiver C, Brouqui P, Colson P (2011) Hepatitis E virus infection in patients infected with the human immunodeficiency virus. J Med Virol 83:1704–1716CrossRefPubMedGoogle Scholar
  30. 30.
    Kamar N, Selves J, Mansuy JM, Ouezzani L, Peron JM, Guitard J, Cointault O, Esposito L, Abravanel F, Danjoux M, Durand D, Vinel JP, Izopet J, Rostaing L (2008) Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 358:811–817CrossRefPubMedGoogle Scholar
  31. 31.
    Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J, Dalton HR (2012) Hepatitis E. Lancet 379:2477–2488CrossRefPubMedGoogle Scholar
  32. 32.
    Kamar N, Dalton HR, Abravanel F, Izopet J (2014) Hepatitis E virus infection. Clin Microbiol Rev 27:116–138CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Keane F, Gompels M, Bendall R, Drayton R, Jennings L, Black J, Baragwanath G, Lin N, Henley W, Ngui SL, Ijaz S, Dalton H (2012) Hepatitis E virus coinfection in patients with HIV infection. HIV Med 13:83–88PubMedGoogle Scholar
  34. 34.
    Kenfak-Foguena A, Schoni-Affolter F, Burgisser P, Witteck A, Darling KE, Kovari H, Kaiser L, Evison JM, Elzi L, Gurter-De La Fuente V, Jost J, Moradpour D, Abravanel F, Izpopet J, Cavassini M (2011) Hepatitis E virus seroprevalence and chronic infections in patients with HIV, Switzerland. Emerg Infect Dis 17:1074–1078CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Khudyakov Y, Kamili S (2011) Serological diagnostics of hepatitis E virus infection. Virus Res 161:84–92CrossRefPubMedGoogle Scholar
  36. 36.
    Koning L, Pas SD, de Man RA, Balk AHMM, de Knegt RJ, ten Kate FJ, Osterhaus ADME, van der Eijk AA (2013) Clinical implications of chronic hepatitis E virus infection in heart transplant recipients. J Heart Lung Transplant 32:78–85CrossRefPubMedGoogle Scholar
  37. 37.
    Kuniholm MH, Ong E, Hogema BM, Koppelman M, Anastos K, Peters MG, Seaberg EC, Chen Y, Nelson KE, Linnen JM (2016) Acute and chronic hepatitis E virus infection in human immunodeficiency virus-infected U.S. women. Hepatology 63:712–720CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lee G-H, Tan B-H, Teo EC-Y, Lim S-G, Dan Y-Y, Wee A, Aw PPK, Zhu Y, Hibberd ML, Tan C-K, Purdy MA, Teo C-G (2015) Chronic infection with Camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk. Gastroenterology 170(2):355–357.e3. doi:  10.1053/j.gastro.2015.10.048
  39. 39.
    Lyra AC, Pinho JR, Silva LK, Sousa L, Saraceni CP, Braga EL, Pereira JE, Zarife MA, Reis MG, Lyra LG, Silva LC, Carrilho FJ (2005) HEV, TTV and GBV-C/HGV markers in patients with acute viral hepatitis. Braz J Med Biol Res 38:767–775CrossRefPubMedGoogle Scholar
  40. 40.
    Martins RM, Freitas NR, Kozlowski A, Reis NR, Lopes CL, Teles SA, Gardinali NR, Pinto MA (2014) Seroprevalence of hepatitis E antibodies in a population of recyclable waste pickers in Brazil. J Clin Virol Off Publ Pan Am Soc Clin Virol 59:188–191CrossRefGoogle Scholar
  41. 41.
    Maylin S, Stephan R, Molina JM, Peraldi MN, Scieux C, Nicand E, Simon F, Delaugerre C (2012) Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised. J Clin Virol Off Publ Pan Am Soc Clin Virol 53:346–349CrossRefGoogle Scholar
  42. 42.
    Neukam K, Barreiro P, Macias J, Avellon A, Cifuentes C, Martin-Carbonero L, Echevarria JM, Vargas J, Soriano V, Pineda JA (2013) Chronic hepatitis E in HIV patients: rapid progression to cirrhosis and response to oral ribavirin. Clin Infect Dis Off Publ Infect Dis Soc Am 57:465–468CrossRefGoogle Scholar
  43. 43.
    Paiva HH, Tzaneva V, Haddad R, Yokosawa J (2007) Molecular characterization of swine hepatitis E virus from southeastern Brazil. Braz J Microbiol 38:693–698CrossRefGoogle Scholar
  44. 44.
    Parana R, Cotrim HP, Cortey-Boennec ML, Trepo C, Lyra L (1997) Prevalence of hepatitis E virus IgG antibodies in patients from a referral unit of liver diseases in Salvador, Bahia, Brazil. Am J Trop Med Hyg 57:60–61CrossRefPubMedGoogle Scholar
  45. 45.
    Passos-Castilho AM, Porta G, Miura IK, Pugliese RP, Danesi VL, Porta A, Guimaraes T, Seda J, Antunes E, Granato CF (2014) Chronic hepatitis E virus infection in a pediatric female liver transplant recipient. J Clin Microbiol 52:4425–4427CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Passos-Castilho AM, de Sena A, Geraldo A, Spada C, Granato CFH (2015) High prevalence of hepatitis E virus antibodies among blood donors in Southern Brazil. J Med Virol. doi: 10.1002/jmv.24336
  47. 47.
    Passos-Castilho AM, Reinaldo MR, de Sena A, Granato CFH (2017) High prevalence of hepatitis E virus antibodies in Sao Paulo, Southeastern Brazil: analysis of a group of blood donors representative of the general population. Braz J Infect Dis. doi:  10.1016/j.bjid.2017.05.004
  48. 48.
    Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N, Schlue J, Strassburg CP, Lehner F, Raupach R, Bremer B, Magerstedt P, Cornberg M, Seehusen F, Baumgaertner W, Klempnauer J, Izopet J, Manns MP, Grummer B, Wedemeyer H (2010) Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transplant 16:74–82CrossRefGoogle Scholar
  49. 49.
    Politou M, Boti S, Androutsakos T, Valsami S, Pittaras T, Kapsimali V (2015) Seroprevalence of hepatitis E in HIV infected patients in Greece. J Med Virol 87:1517–1520CrossRefPubMedGoogle Scholar
  50. 50.
    Ramezani A, Velayati AA, Khorami-Sarvestani S, Eslamifar A, Mohraz M, Banifazl M, Bidari-Zerehpoosh F, Yaghmaei F, McFarland W, Foroughi M, Keyvani H, Mostafavi E, Aghakhani A (2013) Hepatitis E virus infection in patients infected with human immunodeficiency virus in an endemic area in Iran. Int J STD AIDS 24:769–774CrossRefPubMedGoogle Scholar
  51. 51.
    Rivero-Juarez A, Martinez-Duenas L, Martinez-Peinado A, Camacho A, Cifuentes C, Gordon A, Frias M, Torre-Cisneros J, Pineda JA, Rivero A (2015) Absence of occult hepatitis E virus infection among HIV immunosuppressed patients. J Infect 70:680–683CrossRefPubMedGoogle Scholar
  52. 52.
    Rode OD, Jemersic L, Brnic D, Pandak N, Mikulic R, Begovac J, Vince A (2014) Hepatitis E in patients with hepatic disorders and HIV-infected patients in Croatia: is one diagnostic method enough for hepatitis E diagnosis? Eur J Clin Microbiol 33:2231–2236CrossRefGoogle Scholar
  53. 53.
    Santos DC, Souto FJ, Santos DR, Vitral CL, Gaspar AM (2002) Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro, RJ, Brazil. Mem Inst Oswaldo Cruz 97:637–640CrossRefPubMedGoogle Scholar
  54. 54.
    Scotto G, Grisorio B, Filippini P, Ferrara S, Massa S, Bulla F, Martini S, Filippini A, Tartaglia A, Lo Muzio L, Fazio V (2015) Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in southern Italy. Infect Dis 47:707–713CrossRefGoogle Scholar
  55. 55.
    Singh GJ, Rockwood N, Atkins M, Gazzard B, Ijaz S, Tedder R, Nelson M (2011) Chronic hepatitis E in HIV as a cause for cryptogenic cirrhosis. HIV Med 12:44Google Scholar
  56. 56.
    Smith DB, Simmonds P, International Committee on Taxonomy of Viruses Hepeviridae Study Group, Jameel S, Emerson SU, Harrison TJ, Meng XJ, Okamoto H, Van der Poel WH, Purdy MA (2014) Consensus proposals for classification of the family Hepeviridae. J Gen Virol 95:2223–2232CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Souto FJ, Fontes CJ, Parana R, Lyra LG (1997) Short report: further evidence for hepatitis E in the Brazilian Amazon. Am J Trop Med Hyg 57:149–150CrossRefPubMedGoogle Scholar
  58. 58.
    Tamura A, Shimizu YK, Tanaka T, Kuroda K, Arakawa Y, Takahashi K, Mishiro S, Shimizu K, Moriyama M (2007) Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma. Hepatol Res Off J Jpn Soc Hepatol 37:113–120CrossRefGoogle Scholar
  59. 59.
    Trinta KS, Liberto MI, de Paula VS, Yoshida CF, Gaspar AM (2001) Hepatitis E virus infection in selected Brazilian populations. Mem Inst Oswaldo Cruz 96:25–29CrossRefPubMedGoogle Scholar
  60. 60.
    Vitral CL, Pinto MA, Lewis-Ximenez LL, Khudyakov YE, dos Santos DR, Gaspar AM (2005) Serological evidence of hepatitis E virus infection in different animal species from the Southeast of Brazil. Mem Inst Oswaldo Cruz 100:117–122CrossRefPubMedGoogle Scholar
  61. 61.
    Wenzel JJ, Preiss J, Schemmerer M, Huber B, Jilg W (2013) Test performance characteristics of Anti-HEV IgG assays strongly influence hepatitis E seroprevalence estimates. J Infect Dis 207:497–500CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • A. C. Ferreira
    • 1
  • Michele Soares Gomes-Gouvêa
    • 1
  • G. Lisboa-Neto
    • 2
  • M. C. J. Mendes-Correa
    • 2
  • C. M. Picone
    • 3
  • N. A. Salles
    • 4
  • A. Mendrone-Junior
    • 4
  • F. J. Carrilho
    • 1
  • J. R. R. Pinho
    • 1
    • 5
  1. 1.Laboratorio de Gastroenterologia e Hepatologia Tropical LIM/07, Instituto de Medicina Tropical da USP, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil
  2. 2.Laboratorio de Virologia LIM/52, Instituto de Medicina Tropical da USP, Departamento de Doenças Infecciosas e Parasitarias, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil
  3. 3.Departamento de Doenças Infecciosas e Parasitarias, Hospital das Clinicas HCFMUSP, Faculdade de MedicinaUniversidade de Sao Paulo, Sao PauloSPBrazil
  4. 4.Fundação Pró-Sangue Hemocentro de São PauloSão PauloBrazil
  5. 5.Hospital Israelita Albert EinsteinSão PauloBrazil

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