Skip to main content
SpringerLink
Log in

Laboratory Diagnosis of HEV Infection

  • Chapter
  • First Online:
Hepatitis E Virus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 948))

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, HEV RNA, and serum antibodies against HEV (immunoglobulin [Ig]A, IgM, and IgG). Anti-HEV IgM antibodies can be detected during the acute phase of the illness and can last approximately 4 or 5 months, representing recent exposure, whereas anti-HEV IgG antibodies can last more than 10 years, representing remote exposure. Thus, the diagnosis of acute infection is based on the presence of anti-HEV IgM, 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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ALF:

acute liver failure

ALP:

alkaline phosphatase

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

EIA:

enzyme immunoassay

GGT:

γ-glutamyl transferase

HEV:

Hepatitis E Virus

IgA:

immunoglobulin A

IgG:

immunoglobulin G

IgM:

immunoglobulin M

ORF:

Open reading frame

TBA:

total iron binding capacity

References

  1. Aggarwal R (2013) Diagnosis of hepatitis E. Nat Rev Gastroenterol Hepatol 10(1):24–33

    Article  CAS  PubMed  Google Scholar 

  2. Arankalle VA, Lole KS, Deshmukh TM, Chobe LP, Gandhe SS (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 

  3. 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 

  4. 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(1):23–31

    Article  CAS  PubMed  Google Scholar 

  5. Baylis SA, Hanschmann KM, Blumel J, Nubling CM, Group, H.E.V.C.S (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 

  6. 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 

  7. Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, Teo CG (2006) Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus Med 16(2):79–83

    Article  CAS  PubMed  Google Scholar 

  8. Bradley DW, Krawczynski K, Humphrey CD, McCaustland KA (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 

  9. Bryan JP, Tsarev SA, Iqbal M, Ticehurst J, Emerson S, Ahmed A, Duncan J, Rafiqui AR, Malik IA, Purcell RH 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 170(3):517–521

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 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 

  12. 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 

  13. Chen HY, Lu Y, Howard T, Anderson D, Fong PY, Hu WP, Chia CP, Guan M (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 

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

    Article  Google Scholar 

  15. CMDA (2009) Standard of diagnosis and treatment of hepatitis E. Chin J Clin Infect Dis 2(5):260–263

    Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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 

  18. 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 

  19. 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 

  20. Emerson SU, Purcell RH (2003) Hepatitis E virus. Rev Med Virol 13(3):145–154

    Article  CAS  PubMed  Google Scholar 

  21. Favorov MO, Fields HA, Purdy MA, Yashina TL, Aleksandrov AG, Alter MJ, Yarasheva DM, Bradley DW, Margolis HS (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 

  22. Favorov MO, Khudyakov YE, Fields HA, Khudyakova NS, Padhye N, Alter MJ, Mast E, Polish L, Yashina TL, Yarasheva DM 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 

  23. Feng R, Zhao C, Li M, Harrison TJ, Qiao Z, Feng Y, Ma Z, Wang Y (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 

  24. 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 

  25. Geng JB, Fu HW, Wang L, Wang XJ, Guan JM, Chang YB, Li LJ, Zhu YH, Zhuang H, Liu QH, 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 = Zhonghua liuxingbingxue zazhi 31(1):47–50

    CAS  PubMed  Google Scholar 

  26. Geng Y, Wang C, Zhao C, Yu X, Harrison TJ, Tian K, Wang Y (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):765–770

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  28. Geng Y, Zhao C, Song A, Wang J, Zhang X, Harrison TJ, Zhou Y, Wang W, Wang Y (2011) The serological prevalence and genetic diversity of hepatitis E virus in farmed rabbits in China. Infect Genet Evol 11(2):476–482

    Article  PubMed  Google Scholar 

  29. Gerolami 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 

  30. 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. Journal Clin Virol 58(2):374–377

    Article  CAS  Google Scholar 

  31. 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 

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

    Article  PubMed  Google Scholar 

  33. 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 Transpl 14(4):547–553

    Article  PubMed  Google Scholar 

  34. Haim-Boukobza S, Ferey MP, Vetillard AL, Jeblaoui A, Pelissier E, Pelletier G, Teillet L, Roque-Afonso AM (2012) Transfusion-transmitted hepatitis E in a misleading context of autoimmunity and drug-induced toxicity. J Hepatol 57(6):1374–1378

    Article  CAS  PubMed  Google Scholar 

  35. Herremans M, Bakker J, Duizer E, Vennema H, Koopmans MP (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 

  36. Hu WP, Lu Y, Precioso NA, Chen HY, Howard T, Anderson D, Guan M (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):1151–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Im SW, Zhang JZ, Zhuang H, Che XY, Zhu WF, Xu GM, Li K, Xia NS, Ng MH (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 

  38. 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(4):263–270

    Article  CAS  PubMed  Google Scholar 

  39. Jimenez de Oya N, 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  PubMed  PubMed Central  Google Scholar 

  40. 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 

  41. 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 

  42. 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(8):811–817

    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. 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 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  48. 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 

  49. 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. Journal Infect Dis 200(1):48–56

    Article  Google Scholar 

  50. Lee YH, Ha Y, Ahn KK, Cho KD, Lee BH, Kim SH, Chae C (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 

  51. 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 

  52. Li SW, Zhang J, Li YM, Ou SH, Huang GY, He ZQ, Ge SX, Xian YL, Pang SQ, Ng MH, Xia NS (2005) A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine 23(22):2893–2901

    Article  CAS  PubMed  Google Scholar 

  53. Ma H, Song X, Li Z, Harrison TJ, Zhang H, Huang W, Hao W, Kong W, Wang Y (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 81(6):1052–1061

    Article  CAS  PubMed  Google Scholar 

  54. Ma Y, Lin SQ, Gao Y, Li M, Luo WX, Zhang J, Xia NS (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 

  55. Mansuy JM, Peron JM, Abravanel F, Poirson H, Dubois M, Miedouge M, Vischi F, Alric L, Vinel JP, Izopet J (2004) Hepatitis E in the south west of France in individuals who have never visited an endemic area. J Med Virol 74(3):419–424

    Article  PubMed  Google Scholar 

  56. 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 

  57. Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, Sato S, Kato T, Nishimori H, Tsuji K, Maguchi H, Yoshida J, Maekubo H, Mishiro S, Ikeda H (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 

  58. Matsubayashi K, Nagaoka Y, Sakata H, Sato S, Fukai K, Kato T, Takahashi K, Mishiro S, Imai M, Takeda N, Ikeda H (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 

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

    Article  CAS  PubMed  Google Scholar 

  60. Meng XJ, Wiseman B, Elvinger F, Guenette DK, Toth TE, Engle RE, Emerson SU, Purcell RH (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 

  61. 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 

  62. Myint KS, Guan M, Chen HY, Lu Y, Anderson D, Howard T, Noedl H, Mammen MP Jr (2005) Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute hepatitis E infection. AmJTrop Med Hyg 73(5):942–946

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  64. Paul DA, Knigge MF, Ritter A, Gutierrez R, Pilot-Matias T, Chau KH, Dawson GJ (1994) Determination of hepatitis E virus seroprevalence by using recombinant fusion proteins and synthetic peptides. Journal Infect Dis 169(4):801–806

    Article  CAS  Google Scholar 

  65. 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 

  66. Qi Z, Cui D, Pan W, Yu C, Song Y, Cui H, Arima T (1995) Synthesis and application of hepatitis E virus peptides to diagnosis. J Virol Methods 55(1):55–66

    Article  CAS  PubMed  Google Scholar 

  67. Ren F, Zhao C, Wang L, Wang Z, Gong X, Song M, Zhuang H, Huang Y, Shan H, Wang J, Liu Q, Ness P, Nelson KE, Wang Y (2014) Hepatitis E virus seroprevalence and molecular study among blood donors in China. Transfusion 54(3 Pt 2):910–917

    Article  CAS  PubMed  Google Scholar 

  68. 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):8011–8017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Robinson RA, Burgess WH, Emerson SU, Leibowitz RS, Sosnovtseva SA, Tsarev S, Purcell RH (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 

  70. Sakata H, Matsubayashi K, Takeda H, Sato S, Kato T, Hino S, Tadokoro K, Ikeda H (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 

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

    Article  PubMed  Google Scholar 

  72. Takahashi M, Kusakai S, Mizuo H, Suzuki K, Fujimura K, Masuko K, Sugai Y, Aikawa T, Nishizawa T, Okamoto H (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):49–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 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. Journal Infect Dis 209(6):837–844

    Article  Google Scholar 

  74. 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 Gene Virol 84(Pt 2):421–427

    Article  CAS  Google Scholar 

  75. Tsarev SA, Tsareva TS, Emerson SU, Kapikian AZ, Ticehurst J, London W, Purcell RH (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. Journal Infect Dis 168(2):369–378

    Article  CAS  Google Scholar 

  76. 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 

  77. Wang Y, Ling R., Erker JC., Zhang H, Li H, Desai S, Mushahwar IK, Harrison TJ (1999) A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. J Gen Virol 80(Pt 1):169–177

    Google Scholar 

  78. Wang YC, Zhang HY, Xia NS, Peng G, Lan HY, Zhuang H, Zhu YH, Li SW, Tian KG, Gu WJ, Lin JX, Wu X, Li HM, Harrison TJ (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 

  79. 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 

  80. Zhang F, Li X, Li Z, Harrison TJ, Chong H, Qiao S, Huang W, Zhang H, Zhuang H, Wang Y (2006) Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E. J Med Virol 78(11):1441–1448

    Article  CAS  PubMed  Google Scholar 

  81. Zhang JZ, Ng MH, Xia NS, Lau SH, Che XY, Chau TN, Lai ST, Im SW (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 

  82. Zhang M, Emerson SU, Nguyen H, Engle RE, Govindarajan S, Gerin JL, Purcell RH (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 

  83. 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 

  84. Zhao C, Li L, Harrison TJ, Wang Q, Song A, Fan J, Ma H, Zhang C, Wang Y (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 

  85. Zhao C, Li Z, Yan B, Harrison TJ, Guo X, Zhang F, Yin J, Yan Y, Wang Y (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 

  86. Zhao C, Ma Z, Harrison TJ, Feng R, Zhang C, Qiao Z, Fan J, Ma H, Li M, Song A, Wang Y (2009) A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol 81(8):1371–1379

    Article  CAS  PubMed  Google Scholar 

  87. 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 

  88. Zhou YX, Lee MY, Ng JM, Chye ML, Yip WK, Zee SY, Lam E (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 

  89. Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS (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 

  90. Zhu X, Zhuang H, Zhu W, Zhu Y, Ma W, Chen Y, Lou G (1997) Partial nucleotide sequencing of hepatitis E virus isolated from sera of patients with acute sporadic hepatitis E in China. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 11(2):137–140

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China

    Chenyan Zhao Ph.D. & Youchun Wang M.D., Ph.D.

Authors
  1. Chenyan Zhao Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Youchun Wang M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Youchun Wang M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China

    Youchun Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Zhao, C., Wang, Y. (2016). Laboratory Diagnosis of HEV Infection. In: Wang, Y. (eds) Hepatitis E Virus. Advances in Experimental Medicine and Biology, vol 948. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0942-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation