Abstract
The anti-hepatitis E virus (HEV) immunoglobulin (Ig) M antibody response is generally regarded as a useful marker for diagnosing primary infection. However, in some cases, this antibody is not detected during the acute phase of infection. An 81-year-old man with stable membranous nephropathy who presented with asymptomatic acute liver dysfunction came to our hospital. HEV RNA of genotype 3 was detected in his serum, and he was diagnosed with acute hepatitis E. According to an enzyme-linked immunosorbent assay, high-level positivity for anti-HEV IgG and IgA antibodies was observed, but the assay was negative for IgM antibody throughout the clinical course of infection. The patient was not immunosuppressed. We further investigated the presence of IgM antibody using two other polyclonal antibodies against human IgM as secondary antibodies and another recombinant ORF2 protein of genotype 3 as an immobilized antigen. IgM was weakly detected in the serum during the acute phase only by the test with the antigen of genotype 3. Multi-genotype antigens can detect a slight IgM antibody response; however, anti-HEV IgA is more useful in diagnosing primary HEV infection, particularly in cases with a low IgM antibody response.
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References
Purcell RH, Emerson SU. Hepatitis E: an emerging awareness of an old disease. J Hepatol. 2008;48:494–503.
Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012;379:2477–88.
Mizuo H, Yazaki Y, Sugawara K, et al. Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan. J Med Virol. 2005;76:341–9.
Mitsui T, Tsukamoto Y, Hirose A, et al. Distinct changing profiles of hepatitis A and E virus infection among patients with acute hepatitis, patients on maintenance hemodialysis and healthy individuals in Japan. J Med Virol. 2006;78:1015–24.
Takahashi M, Okamoto H. Features of hepatitis E virus infection in humans and animals in Japan. Hepatol Res. 2014;44:43–58.
Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012;367:1237–44.
Mitsui T, Tsukamoto Y, Suzuki S, et al. Serological and molecular studies on subclinical hepatitis E virus infection using periodic serum samples obtained from healthy individuals. J Med Virol. 2005;76:526–33.
Takikawa Y, Miyamoto Y, Onodera M, et al. Icteric acute hepatitis E with no response of immunoglobulin M class anti-hepatitis E virus antibody. Hepatol Res. 2012;42:1146–9.
Okamoto H, Mishiro S, Tokita H, et al. Superinfection of chimpanzees carrying hepatitis C virus of genotype II/1b with that of genotype III/2a or I/1a. Hepatology. 1994;20:1131–6.
Takikawa H, Onji M. A proposal of the diagnostic scale of drug induced liver injury. Hepatol Res. 2005;32:250–1.
Mizuo H, Suzuki K, Takikawa Y, et al. Polyphyletic strains of hepatitis E virus are responsible for sporadic cases of acute hepatitis in Japan. J Clin Microbiol. 2002;40:3209–18.
Takahashi M, Kusakai S, Mizuo H, et al. 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. 2005;43:49–56.
Lu L, Li C, Hagedorn CH. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol. 2006;16:5–36.
Takahashi M, Hoshino Y, Tanaka T, et al. Production of monoclonal antibodies against hepatitis E virus capsid protein and evaluation of their neutralizing activity in a cell culture system. Arch Virol. 2008;153:657–66.
Matsubayashi K, Kang JH, Sakata H, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion. 2008;48:1368–75.
Mitsui T, Tsukamoto Y, Yamazaki C, et al. Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion. J Med Virol. 2004;74:563–72.
Seriwatana J, Shrestha MP, Scott RM, et al. Clinical and epidemiological relevance of quantitating hepatitis E virus-specific immunoglobulin M. Clin Diagn Lab Immunol. 2002;9:1072–8.
Bendall R, Ellis V, Ijaz S, et al. Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM response. J Med Virol. 2008;80:95–101.
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This study was supported in part by the Ministry of Health, Labor, and Welfare of Japan (H24-Hepatitis-General-002).
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All experimental procedures were in accordance with the ethical standards of the responsible committee on human experimentation and the 2008 revision of the Helsinki Declaration of 1975.
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Inagaki, Y., Oshiro, Y., Imanishi, M. et al. Acute infection by hepatitis E virus with a slight immunoglobulin M antibody response. Clin J Gastroenterol 8, 247–252 (2015). https://doi.org/10.1007/s12328-015-0589-4
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DOI: https://doi.org/10.1007/s12328-015-0589-4