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Laboratory Diagnosis of HEV Infection

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Hepatitis E Virus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1417))

Abstract

Serological and nucleic acid tests for detecting hepatitis E virus (HEV) have been developed for both epidemiologic and diagnostic purposes. The laboratory diagnosis of HEV infection depends on the detection of HEV antigen or HEV RNA in the blood, stool, and other body fluids, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies and low avidity IgG can be detected during the acute phase of the illness and can last approximately 12 months, representing primary infection, whereas anti-HEV IgG antibodies can last more than several years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, low avidity IgG, HEV antigen, and HEV RNA, while epidemiological investigations are mainly based on anti-HEV IgG. Although significant progress has been made in developing and optimizing different formats of HEV assays, improving their sensitivity and specificity, there are many shortcomings and challenges in inter-assay concordance, validation, and standardization. This article reviews the current knowledge on the diagnosis of HEV infection, including the most common available laboratory diagnostic techniques.

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Abbreviations

ALF:

Acute liver failure

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

EASL:

The European Association for the Study of the Liver

EIA:

Enzyme immunoassay

GGT:

γ-glutamyl transferase

HEV:

Hepatitis E Virus

IgA:

Immunoglobulin A

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

IS:

International Standard

NAT:

Nucleic acid amplification technology

ORF:

Open reading frame

TBA:

Total iron binding capacity

References

  1. 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(10):1025–1027

    Article  CAS  PubMed  Google Scholar 

  2. Kamar N, Selves J, Mansuy JM, Ouezzani L, Péron J, Guitard J et al (2008) Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 358(8):811–817

    Article  CAS  PubMed  Google Scholar 

  3. Balayart MS, Andjaparidze AG, Savinskaya SS, Ketiladze ES, Braginsky DM, Savinov AP et al (1983) Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 20(1):23–31

    Article  Google Scholar 

  4. Khuroo MS (2011) Discovery of hepatitis E: the epidemic non-A, non-B hepatitis 30 years down the memory lane. Virus Res 161(1):3–14

    Article  CAS  PubMed  Google Scholar 

  5. Miyamura T (2011) Hepatitis E virus infection in developed countries. Virus Res 161(1):40–46

    Article  CAS  PubMed  Google Scholar 

  6. Murrison LB, Sherman KE (2017) The enigma of hepatitis E virus. Gastroenterol Hepatol 13(8):484–491

    Google Scholar 

  7. Pilar CC, Carlota RR, Eugenio RG, Antonio M (2016) Hepatitis E virus in industrialized countries: the silent threat. Biomed Res Int 2016:1–17

    Google Scholar 

  8. Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ et al (2010) Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 376(9744):895–902

    Article  CAS  PubMed  Google Scholar 

  9. Bradley D, Krawczynski K, Humphrey C, Mccaustland K (1987) Biochemically silent posttransfusion non-A, non-B hepatitis interferes with superinfection by hepatitis A virus. Intervirology 27(2):86–90

    Article  CAS  PubMed  Google Scholar 

  10. Krawczynski K, Bradley DW (1989) Enterically transmitted non-A, non-B hepatitis: identification of virus-associated antigen in experimentally infected cynomolgus macaques. J Infect Dis 159(6):1042–1049

    Article  CAS  PubMed  Google Scholar 

  11. Khuroo MS, Rustgi VK, Dawson GJ, Mushahwar IK, Yattoo GN, Kamili S et al (1994) Spectrum of hepatitis E virus infection in India. J Med Virol 43(3):281–286

    Article  CAS  PubMed  Google Scholar 

  12. Krawczynski K, Meng XJ, Rybczynska J (2011) Pathogenetic elements of hepatitis E and animal models of HEV infection. Virus Res 161(1):78–83

    Article  CAS  PubMed  Google Scholar 

  13. Geng Y, Zhao C, Huang W, Harrison TJ, Zhang H, Geng K et al (2016) Detection and assessment of infectivity of hepatitis E virus in urine. J Hepatol 64(1):37–43

    Article  PubMed  Google Scholar 

  14. Mushahwar IK (2008) Hepatitis E virus: molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J Med Virol 80(4):646–658

    Article  PubMed  Google Scholar 

  15. European Association for the Study of the Liver (2018) EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol 68(6):1256–1271

    Article  Google Scholar 

  16. Favorov MO, Fields HA, Purdy MA, Yashina TL, Aleksandrov AG, Alter MJ et al (1992) Serologic identification of hepatitis E virus infections in epidemic and endemic settings. J Med Virol 36(4):246–250

    Article  CAS  PubMed  Google Scholar 

  17. Huang S, Zhang X, Jiang H, Yan Q, Ai X, Wang Y et al (2010) Profile of acute infectious markers in sporadic hepatitis E. PLoS One 5(10):e13560

    Article  PubMed  PubMed Central  Google Scholar 

  18. Takahashi M, Kusakai S, Mizuo H, Suzuki K, Fujimura K, Masuko K et al (2005) Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) is highly specific for diagnosis of acute HEV infection. J Clin Microbiol 43(1):49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bryan JP, Tsarev SA, Mohammed I, John T, Suzanne E, Aftab A et al (1994) Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease. J Infect Dis 3:517–521

    Article  Google Scholar 

  20. Dawson GJ, Chau KH, Cabal CM, Yarbough PO, Reyes GR, Mushahwar IK (1992) Solid-phase enzyme-linked immunosorbent assay for hepatitis E virus IgG and IgM antibodies utilizing recombinant antigens and synthetic peptides. J Virol Methods 38(1):175–186

    Article  CAS  PubMed  Google Scholar 

  21. Khuroo MS, Kamili S, Dar MY, Moecklii R, Jameel S (1993) Hepatitis E and long-term antibody status. Lancet 341(8856):1355

    Article  CAS  PubMed  Google Scholar 

  22. Chau KH, Dawson GJ, Bile KM, Magnius LO, Sjogren MH, Mushahwar IK (1993) Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection. J Med Virol 40(4):334–338

    Article  CAS  PubMed  Google Scholar 

  23. Herremans, Bakker, Duizer, Vennema, Koopmans (2007) Use of serological assays for diagnosis of hepatitis E virus genotype 1 and 3 infections in a setting of low endemicity. Clin Vaccine Immunol 14(5):562–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tokita H, Harada H, Gotanda Y, Takahashi M, Nishizawa T, Okamoto H (2003) Molecular and serological characterization of sporadic acute hepatitis E in a Japanese patient infected with a genotype III hepatitis E virus in 1993. J Gen Virol 84(Pt 2):421–427

    Article  CAS  PubMed  Google Scholar 

  25. Gérolami R, Moal V, Picard C, Colson P (2009) Hepatitis E virus as an emerging cause of chronic liver disease in organ transplant recipients. J Hepatol 50(3):622–624

    Article  PubMed  Google Scholar 

  26. Pischke S, Wedemeyer H (2010) Chronic hepatitis E in liver transplant recipients: a significant clinical problem? Minerva Gastroenterol Dietol 56(2):121–128

    CAS  PubMed  Google Scholar 

  27. Haagsma EB, Niesters HG, van den Berg AP, Riezebos-Brilman A, Porte RJ, Vennema H et al (2009) Prevalence of hepatitis E virus infection in liver transplant recipients. Liver Transpl 15(10):1225–1228

    Article  PubMed  Google Scholar 

  28. Haagsma EB, van den Berg AP, Porte RJ, Benne CA, Vennema H, Reimerink JH et al (2008) Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl 14(4):547–553

    Article  PubMed  Google Scholar 

  29. Dalton HR, Bendall R, Ijaz S, Banks M (2008) Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis 8(11):698–709

    Article  PubMed  Google Scholar 

  30. Li F, Riddell MA, Seow HF, Takeda N, Miyamura T, Anderson DA (2000) Recombinant subunit ORF2.1 antigen and induction of antibody against immunodominant epitopes in the hepatitis E virus capsid protein. J Med Virol 60(4):379–386

    Article  CAS  PubMed  Google Scholar 

  31. Im SW, Zhang JZ, Zhuang H, Che XY, Zhu WF, Xu GM et al (2001) A bacterially expressed peptide prevents experimental infection of primates by the hepatitis E virus. Vaccine 19(27):3726–3732

    Article  CAS  PubMed  Google Scholar 

  32. Jimenez D, Galindo I, Girones O, Duizer E, Escribano JM, Saiz JC (2009) Serological immunoassay for detection of hepatitis E virus on the basis of genotype 3 open reading frame 2 recombinant proteins produced in Trichoplusia ni larvae. J Clin Microbiol 47(10):3276–3282

    Article  Google Scholar 

  33. Ma Y, Lin SQ, Gao Y, Li M, Luo WX, Zhang J et al (2003) Expression of ORF2 partial gene of hepatitis E virus in tomatoes and immunoactivity of expression products. World J Gastroenterol 9(10):2211–2215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Robinson RA, Burgess WH, Emerson SU, Leibowitz RS, Sosnovtseva SA, Tsarev S et al (1998) Structural characterization of recombinant hepatitis E virus ORF2 proteins in baculovirus-infected insect cells. Protein Expr Purif 12(1):75–84

    Article  CAS  PubMed  Google Scholar 

  35. Tsarev SA, Tsareva TS, Emerson SU, Kapikian AZ, Ticehurst J, London W et al (1993) ELISA for antibody to hepatitis E virus (HEV) based on complete open-reading frame-2 protein expressed in insect cells: identification of HEV infection in primates. J Infect Dis 168(2):369–378

    Article  CAS  PubMed  Google Scholar 

  36. Zhang M, Emerson SU, Nguyen H, Engle RE, Govindarajan S, Gerin JL et al (2001) Immunogenicity and protective efficacy of a vaccine prepared from 53 kDa truncated hepatitis E virus capsid protein expressed in insect cells. Vaccine 20(5-6):853–857

    Article  CAS  PubMed  Google Scholar 

  37. Zhou YX, Lee MY, Ng JM, Chye ML, Yip WK, Zee SY et al (2006) A truncated hepatitis E virus ORF2 protein expressed in tobacco plastids is immunogenic in mice. World J Gastroenterol 12(2):306–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Favorov MO, Khudyakov YE, Fields HA, Khudyakova NS, Padhye N, Alter MJ et al (1994) Enzyme immunoassay for the detection of antibody to hepatitis E virus based on synthetic peptides. J Virol Methods 46(2):237–250

    Article  CAS  PubMed  Google Scholar 

  39. Paul DA, Knigge MF, Ritter A, Gutierrez R, Pilot-Matias T, Chau KH et al (1994) Determination of hepatitis E virus seroprevalence by using recombinant fusion proteins and synthetic peptides. J Infect Dis 4:801–806

    Article  Google Scholar 

  40. Qi Z, Cui D, Pan W, Yu C, Song Y, Cui H et al (1995) Synthesis and application of hepatitis E virus peptides to diagnosis. J Virol Methods 55(1):55

    Article  CAS  PubMed  Google Scholar 

  41. Ferguson M, Walker D, Mast E, Fields H (2002) Report of a collaborative study to assess the suitability of a reference reagent for antibodies to hepatitis E virus. Biologicals 30(1):43–48

    Article  CAS  PubMed  Google Scholar 

  42. Mast EE, Alter MJ, Holland PV, Purcell RH (1998) Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group. Hepatology 27(3):857–861

    Article  CAS  PubMed  Google Scholar 

  43. Khudyakov Y, Kamili S (2011) Serological diagnostics of hepatitis E virus infection. Virus Res 161(1):84–92

    Article  CAS  PubMed  Google Scholar 

  44. Riddell MA, Li F, Anderson DA (2000) Identification of immunodominant and conformational epitopes in the capsid protein of hepatitis E virus by using monoclonal antibodies. J Virol 74(17):8011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang JZ, Ng MH, Xia NS, Lau SH, Che XY, Chau TN et al (2001) Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein. J Med Virol 64(2):125–132

    Article  CAS  PubMed  Google Scholar 

  46. Arankalle VA, Lole KS et al (2007) Evaluation of human (genotype 1) and swine (genotype 4)-ORF2-based ELISAs for anti-HEV IgM and IgG detection in an endemic country and search for type 4 human HEV infections. J Viral Hepat 14(6):435–445

    Article  CAS  PubMed  Google Scholar 

  47. Zhou YH, Purcell RH, Emerson SU (2004) An ELISA for putative neutralizing antibodies to hepatitis E virus detects antibodies to genotypes 1, 2, 3, and 4. Vaccine 22(20):2578–2585

    Article  CAS  PubMed  Google Scholar 

  48. Hongxia M, Xiaoguo S, Zhuo L et al (2009) Varying abilities of recombinant polypeptides from different regions of hepatitis E virus ORF2 and ORF3 to detect anti-HEV immunoglobulin M. J Med Virol 16:8

    Google Scholar 

  49. Li SW, Zhang J, Li YM, Ou SH, Huang GY, He ZQ et al (2005) A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine 23(22):2893–2901

    Article  CAS  PubMed  Google Scholar 

  50. Meng J, Dai X, Chang JC, Lopareva E, Pillot J, Fields HA et al (2001) Identification and characterization of the neutralization epitope(s) of the hepatitis E virus. Virology 288(2):203–211

    Article  CAS  PubMed  Google Scholar 

  51. Christensen PB, Engle RE, Hjort C, Homburg KM, Vach W, Georgsen J et al (2008) Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin Infect Dis 47(8):1026–1031

    Article  PubMed  Google Scholar 

  52. Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE (2009) Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988-1994. J Infect Dis 200(1):48–56

    Article  PubMed  Google Scholar 

  53. Tarter KD, Simanek AM, Dowd JB, Aiello AE (2014) Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey. J Infect Dis 209(6):837–844

    Article  PubMed  Google Scholar 

  54. Adekunle O, Dretler A, Kauffman RC, Cho A, Rouphael N, Wrammert J (2021) Longitudinal analysis of human humoral responses after vaccination with a live attenuated V. cholerae vaccine. PLoS Negl Trop Dis 15(9):e0009743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Champsaur A, Fattal-German A, Arranhado A (1988) Sensitivity and specificity of viral immunoglobulin M determination by indirect enzyme-linked immunosorbent assay. J Clin Microbiol 26(2):328–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Yu C, Engle RE, Bryan JP, Emerson SU, Purcell RH (2003) Detection of immunoglobulin M antibodies to hepatitis E virus by class capture enzyme immunoassay. Clin Diagn Lab Immunol 10(4):579–586

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Baechlein C, Schielke A, Johne R, Ulrich RG, Baumgaertner W, Grummer B (2010) Prevalence of hepatitis E virus-specific antibodies in sera of German domestic pigs estimated by using different assays. Vet Microbiol 144(1-2):187–191

    Article  PubMed  Google Scholar 

  58. Bendall R, Ellis V, Ijaz S, Thurairajah P, Dalton HR (2008) Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM response. J Med Virol 80(1):95–101

    Article  CAS  PubMed  Google Scholar 

  59. Skidmore S (2002) Overview of hepatitis E virus. Curr Infect Dis Rep 4(2):118–123

    Article  PubMed  Google Scholar 

  60. Kneitz RH, Schubert J, Tollmann F, Zens W, Hedman K, Weissbrich B (2004) A new method for determination of varicella-zoster virus immunoglobulin G avidity in serum and cerebrospinal fluid. BMC Infect Dis 4:33

    Article  PubMed  PubMed Central  Google Scholar 

  61. Prince HE, Wilson M (2001) Simplified assay for measuring Toxoplasma gondii immunoglobulin G avidity. Clin Diagn Lab Immunol 8(5):904–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Baylis SA, Crossan C, Corman VM, Blumel J, Scobie L, Dalton HR (2015) Unusual serological response to hepatitis E virus in plasma donors consistent with re-infection. Vox Sang 109(4):406–409

    Article  CAS  PubMed  Google Scholar 

  63. Bigaillon C, Tessé S, Lagathu G, Nicand E (2010) Use of hepatitis E IgG avidity for diagnosis of hepatitis E infection. J Virol Methods 164(1-2):127–130

    Article  CAS  PubMed  Google Scholar 

  64. Minosse C, Lapa D, Coppola A, Rapagna F, D’Offizi G, Taibi C et al (2021) Anti-HEV IgG avidity testing: utility for diagnosing acute and resolved genotype 3 infections. Viruses 13(2):236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wang YC, Zhang HY, Xia NS, Peng G, Lan HY, Zhuang H et al (2002) Prevalence, isolation, and partial sequence analysis of hepatitis E virus from domestic animals in China. J Med Virol 67(4):516–521

    Article  CAS  PubMed  Google Scholar 

  66. Hu WP, Lu Y, Precioso NA, Chen HY, Howard T, Anderson D et al (2008) Double-antigen enzyme-linked immunosorbent assay for detection of hepatitis E virus-specific antibodies in human or swine sera. Clin Vaccine Immunol 15(8):1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen HY, Lu Y, Howard T, Anderson D, Fong PY, Hu WP et al (2005) Comparison of a new immunochromatographic test to enzyme-linked immunosorbent assay for rapid detection of immunoglobulin m antibodies to hepatitis e virus in human sera. Clin Diagn Lab Immunol 12(5):593–598

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kar P, Sengupta A (2019) A guide to the management of hepatitis E infection during pregnancy. Expert Rev Gastroenterol Hepatol 13(3):205–211

    Article  CAS  PubMed  Google Scholar 

  69. Myint KS, Guan M, Chen HY, Lu Y, Anderson D, Howard T et al (2005) Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute hepatitis E infection. Am J Trop Med Hyg 73(5):942–946

    Article  CAS  PubMed  Google Scholar 

  70. Abravanel F, Lhomme S, Chapuy-Regaud S, Peron JM, Alric L, Rostaing L et al (2015) Performance of a new rapid test for detecting anti-hepatitis E virus immunoglobulin M in immunocompetent and immunocompromised patients. J Clin Virol 70:101–104

    Article  CAS  PubMed  Google Scholar 

  71. Feng Z, Xiuhua L, Zhuo L et al (2006) Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E. J Med Virol 78(11):1441–1448

    Article  Google Scholar 

  72. Gupta E, Pandey P, Pandey S, Sharma MK, Sarin SK (2013) Role of hepatitis E virus antigen in confirming active viral replication in patients with acute viral hepatitis E infection. J Clin Virol 58(2):374–377

    Article  CAS  PubMed  Google Scholar 

  73. Vollmer T, Knabbe C, Dreier J (2014) Comparison of real-time PCR and antigen assays for detection of hepatitis E virus in blood donors. J Clin Microbiol 52(6):2150–2156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wen GP, Tang ZM, Yang F, Zhang K, Ji WF, Cai W et al (2015) A valuable antigen detection method for diagnosis of acute hepatitis E. J Clin Microbiol 53(3):782–788

    Article  PubMed  PubMed Central  Google Scholar 

  75. Zhang H, Rao H, Wang Y, Wang J, Kong X, Ji Y et al (2019) Evaluation of an antigen assay for diagnosing acute and chronic hepatitis E genotype 4 infection. J Gastroenterol Hepatol 34(2):458–465

    Article  CAS  PubMed  Google Scholar 

  76. Zhao C, Geng Y, Harrison TJ, Huang W, Song A, Wang Y (2015) Evaluation of an antigen-capture EIA for the diagnosis of hepatitis E virus infection. J Viral Hepat 22(11):957–963

    Article  CAS  PubMed  Google Scholar 

  77. Zhao C, Li L, Harrison TJ, Wang Q, Song A, Fan J et al (2009) Relationships among viral diagnostic markers and markers of liver function in acute hepatitis E. J Gastroenterol 44(2):139–145

    Article  CAS  PubMed  Google Scholar 

  78. Behrendt P, Bremer B, Todt D, Brown RJ, Heim A, Manns MP et al (2016) Hepatitis E virus (HEV) ORF2 antigen levels differentiate between acute and chronic HEV infection. J Infect Dis 214(3):361–368

    Article  CAS  PubMed  Google Scholar 

  79. Ren F, Zhao C, Wang L, Wang Z, Gong X, Song M et al (2014) Hepatitis E virus seroprevalence and molecular study among blood donors in China. Transfusion 54(3):910–917

    Article  CAS  PubMed  Google Scholar 

  80. Geng JB, Fu HW, Wang L, Wang XJ, Peng XC (2010) Hepatitis E virus (HEV) genotype and the prevalence of anti-HEV in 8 species of animals in the suburbs of Beijing. Zhonghua Liu Xing Bing Xue Za Zhi 31(1):47–50

    CAS  PubMed  Google Scholar 

  81. Geng Y, Wang C, Zhao C, Yu X, Harrison TJ, Tian K et al (2010) Serological prevalence of hepatitis E virus in domestic animals and diversity of genotype 4 hepatitis E virus in China. Vector Borne Zoonotic Dis 10(8):765

    Article  PubMed  Google Scholar 

  82. Geng Y, Zhao C, Song A, Wang J, Xiao Z, Harrison TJ et al (2011) The serological prevalence and genetic diversity of hepatitis E virus in farmed rabbits in China. Inf Genet Evol J Mol Epidemiol Evol Genet Inf Dis 11(2):476–482

    Google Scholar 

  83. Zhao C, Ma Z, Harrison TJ, Feng R, Zhang C, Qiao Z et al (2009) A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol 2009:21536

    Google Scholar 

  84. Feng R, Zhao C, Li M, Harrison TJ, Qiao Z, Feng Y et al (2011) Infection dynamics of hepatitis E virus in naturally infected pigs in a Chinese farrow-to-finish farm. Infect Genet Evol 11(7):1727–1731

    Article  PubMed  Google Scholar 

  85. Jameel S, Durgapal H, Habibullah CM, Khuroo MS, Panda SK (1992) Enteric non-A, non-B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction. J Med Virol 37:263

    Article  CAS  PubMed  Google Scholar 

  86. 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(1):65–71

    Article  CAS  PubMed  Google Scholar 

  87. Lan X, Yang B, Li BY, Yin XP, Li XR, Liu JX (2009) Reverse transcription-loop-mediated isothermal amplification assay for rapid detection of hepatitis E virus. J Clin Microbiol 4(7):2304–2306

    Article  Google Scholar 

  88. Zhao C, Li Z, Yan B, Harrison TJ, Guo X, Zhang F et al (2007) Comparison of real-time fluorescent RT-PCR and conventional RT-PCR for the detection of hepatitis E virus genotypes prevalent in China. J Med Virol 79(12):1966–1973

    Article  CAS  PubMed  Google Scholar 

  89. Zhu X, Zhuang H, Zhu W (1997) Partial nucleotide sequencing of 7 hepatitis E virus strains isolated from sera of patients with acute sporadic hepatitis E in China. Zhonghua Yi Xue Za Zhi 77(6):447–449

    CAS  PubMed  Google Scholar 

  90. Chauhan A, Jameel S, Dilawari JB, Chawla YK, Kaur U, Ganguly NK (1993) Hepatitis E virus transmission to a volunteer. Lancet 341(8838):149–150

    Article  CAS  PubMed  Google Scholar 

  91. Aggarwal A, Rakesh A (2013) Diagnosis of hepatitis E. Nat Rev Gastroenterol Hepatol 10(1):24–33

    Article  CAS  PubMed  Google Scholar 

  92. Jothikumar N, Lowther JA, Henshilwood K, Lees DN, Hill VR, Vinje J (2005) Rapid and sensitive detection of noroviruses by using TaqMan-based one-step reverse transcription-PCR assays and application to naturally contaminated shellfish samples. Appl Environ Microbiol 71(4):1870–1875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Orru G, Masia G, Orru G, Romano L, Piras V, Coppola RC (2004) Detection and quantitation of hepatitis E virus in human faces by real-time quantitative PCR. J Virol Methods 118(2):77–82

    Article  CAS  PubMed  Google Scholar 

  94. Mansuy JM, Peron JM, Abravanel F, Poirson H, Dubois M, Miedouge M et al (2004) Hepatitis E in the south west of France in individuals who have never visited an endemic area. J Med Virol 74(3):419

    Article  PubMed  Google Scholar 

  95. Baylis SA, Hanschmann KM, Blumel J, Nubling CM (2011) Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance. J Clin Microbiol 49(4):1234–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Baylis SA, Blümel J, Mizusawa S, Matsubayashi K, Hanschmann K (2013) World Health Organization International standard to harmonize assays for detection of hepatitis E virus RNA. Emerg Infect Dis 19(5):729–735

    Article  PubMed  PubMed Central  Google Scholar 

  97. Colson P, Coze C, Gallian P, Henry M, Micco PD, Tamalet C (2007) Transfusion-associated hepatitis E, France. Emerg Infect Dis 13(4):648–649

    Article  PubMed  PubMed Central  Google Scholar 

  98. Boxall E, Herborn A, Kochethu G et al (2006) Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus Med 16(2):79–83

    Article  CAS  PubMed  Google Scholar 

  99. Ham-Boukobza S, Ferey MP, Vétillard A, Jeblaoui A, Pélissier E, Pelletier G et al (2012) Transfusion-transmitted hepatitis E in a misleading context of autoimmunity and drug-induced toxicity. J Hepatol 57(6):1374–1378

    Article  Google Scholar 

  100. Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M et al (2008) A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion 48(7):1368–1375

    Article  CAS  PubMed  Google Scholar 

  101. Matsubayashi K, Nagaoka Y, Sakata H, Sato S, Fukai K, Kato T et al (2004) Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 44(6):934–940

    Article  PubMed  Google Scholar 

  102. Meng XJ, Wiseman B, Elvinger F, Guenette DK, Toth TE, Engle RE et al (2002) Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol 40(1):117–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Sakata H, Matsubayashi K, Takeda H, Sato S, Kato T, Hino S et al (2008) A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase. Transfusion 48(12):2568–2576

    Article  PubMed  Google Scholar 

  104. Hewitt PE, Ijaz S, Brailsford SR, Brett R, Dicks S, Haywood B et al (2017) Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 384(9956):1766–1773

    Article  Google Scholar 

  105. Gupta P, Jagya N, Pabhu SB, Durgapal H, Acharya SK, Panda SK (2012) Immunohistochemistry for the diagnosis of hepatitis E virus infection. J Viral Hepat 19(2):e177–e183

    Article  CAS  PubMed  Google Scholar 

  106. Lee YH, Ha Y, Ahn KK, Cho KD, Lee BH, Kim SH et al (2009) Comparison of a new synthetic, peptide-derived, polyclonal antibody-based, immunohistochemical test with in situ hybridisation for the detection of swine hepatitis E virus in formalin-fixed, paraffin-embedded tissues. Vet J 182(1):131–135

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Youchun Wang .

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Zhao, C., Wang, Y. (2023). Laboratory Diagnosis of HEV Infection. In: Wang, Y. (eds) Hepatitis E Virus. Advances in Experimental Medicine and Biology, vol 1417. Springer, Singapore. https://doi.org/10.1007/978-981-99-1304-6_14

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