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Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan

Journal of Gastroenterology volume 44, pages 329–337 (2009)Cite this article

Abstract

Background

Recent studies have shown that indigenous hepatitis E virus (HEV) strains cause hepatitis E in industrialized countries. We aimed to clarify the characteristics of HEV infection in sporadic hepatitis patients during the last decade in Miyagi, northeast Japan.

Methods

We analyzed 94 serum samples obtained from acute or fulminant hepatitis patients of non-A, non-B, and non-C etiology between 1999 and 2008. Antibody to HEV (anti-HEV) was assayed, and patients who were positive for IgM- and/or IgA-class anti-HEV were diagnosed with hepatitis E. HEV RNA was tested in these patients, and phylogenetic analysis was performed. The occurrence of hepatitis E was compared with that of hepatitis A.

Results

Eight acute hepatitis patients (8.5%) were diagnosed with hepatitis E, and HEV RNA was detectable in seven patients. Five isolates of HEV were segregated into genotype 3 and the remaining two isolates into genotype 4. The year of the occurrence of hepatitis E was distributed almost equally from 1999 to 2008, whereas the cases of acute hepatitis A (n = 16) have decreased markedly in the last several years. In 2004–2008, the occurrence of hepatitis E was greater than that of hepatitis A (five cases vs. one case). As for seasonality, hepatitis E occurred more frequently from September to December than hepatitis A (five cases vs. four cases), although less frequently from January to April (one case vs. seven cases).

Conclusion

The occurrence of hepatitis E has not decreased during the last decade in northeast Japan, in contrast to hepatitis A.

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References

  1. Purcell RH, Emerson SU. Hepatitis E virus. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, et al., editors. Fields virology. 4th ed. Philadelphia: Lippincott; 2001. p. 3051–61.

    Google Scholar 

  2. Kwo PY, Schlauder GG, Carpenter HA, Murphy PJ, Rosenblatt JE, Dawson GJ, et al. Acute hepatitis E by a new isolate acquired in the United States. Mayo Clin Proc. 1997;72:1133–6.

    PubMed  Article  CAS  Google Scholar 

  3. Harrison TJ. Hepatitis E virus—an update. Liver. 1999;19:171–6.

    PubMed  Article  CAS  Google Scholar 

  4. Smith JL. A review of hepatitis E virus. J Food Prot. 2001;64:572–86.

    PubMed  CAS  Google Scholar 

  5. Okamoto H, Takahashi M, Nishizawa T. Features of hepatitis E virus infection in Japan. Intern Med. 2003;42:1065–71.

    PubMed  Article  CAS  Google Scholar 

  6. Mansuy JM, Peron JM, Abravanel F, Poirson H, Dubois M, Miedouge M, et al. Hepatitis E in the south west of France in individuals who have never visited an endemic area. J Med Virol. 2004;74:419–24.

    PubMed  Article  Google Scholar 

  7. Ijaz S, Arnold E, Banks M, Bendall RP, Cramp ME, Cunningham R, et al. Non-travel-associated hepatitis E in England and Wales: demographic, clinical, and molecular epidemiological characteristics. J Infect Dis. 2005;192:1166–72.

    PubMed  Article  CAS  Google Scholar 

  8. Erker JC, Desai SM, Schlauder GG, Dawson GJ, Mushahwar IK. A hepatitis E virus variant from the United States: molecular characterization and transmission in cynomolgus macaques. J Gen Virol. 1999;80(Pt 3):681–90.

    PubMed  CAS  Google Scholar 

  9. Meng XJ. Novel strains of hepatitis E virus identified from humans and other animal species: is hepatitis E a zoonosis? J Hepatol. 2000;33:842–5.

    PubMed  Article  CAS  Google Scholar 

  10. Meng XJ. Swine hepatitis E virus: cross-species infection and risk in xenotransplantation. Curr Top Microbiol Immunol. 2003;278:185–216.

    PubMed  CAS  Google Scholar 

  11. Meng XJ, Purcell RH, Halbur PG, Lehman JR, Webb DM, Tsareva TS, et al. A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci USA. 1997;94:9860–5.

    PubMed  Article  CAS  Google Scholar 

  12. Nishizawa T, Takahashi M, Mizuo H, Miyajima H, Gotanda Y, Okamoto H. Characterization of Japanese swine and human hepatitis E virus isolates of genotype IV with 99% identity over the entire genome. J Gen Virol. 2003;84:1245–51.

    PubMed  Article  CAS  Google Scholar 

  13. Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–3.

    PubMed  Article  Google Scholar 

  14. Yazaki Y, Mizuo H, Takahashi M, Nishizawa T, Sasaki N, Gotanda Y, et al. Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J Gen Virol. 2003;84:2351–7.

    PubMed  Article  CAS  Google Scholar 

  15. Emerson SU, Anderson D, Arankalle A, Meng XJ, Purdy M, Schlauder GG. Hepevirus. In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA, et al., editors. Virus taxonomy: VIIIth report on the ICTV. London: Elsevier/Academic Press; 2004. p. 851–5.

    Google Scholar 

  16. Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE, et al. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology. 1991;185:120–31.

    PubMed  Article  CAS  Google Scholar 

  17. Wang Y, Zhang H, Ling R, Li H, Harrison TJ. The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3. J Gen Virol. 2000;81:1675–86.

    PubMed  CAS  Google Scholar 

  18. Schlauder GG, Mushahwar IK. Genetic heterogeneity of hepatitis E virus. J Med Virol. 2001;65:282–92.

    PubMed  Article  CAS  Google Scholar 

  19. 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.

    PubMed  Article  CAS  Google Scholar 

  20. Zhai L, Dai X, Meng J. Hepatitis E virus genotyping based on full-length genome and partial genomic regions. Virus Res. 2006;120:57–69.

    PubMed  Article  CAS  Google Scholar 

  21. Okamoto H, Takahashi M, Nishizawa T, Fukai K, Muramatsu U, Yoshikawa A. Analysis of the complete genome of indigenous swine hepatitis E virus isolated in Japan. Biochem Biophys Res Commun. 2001;289:929–36.

    PubMed  Article  CAS  Google Scholar 

  22. Zhang W, Shen Q, Mou J, Gong G, Yang Z, Cui L, et al. Hepatitis E virus infection among domestic animals in Eastern China. Zoonoses Public Health. 2008;55:291–8.

    PubMed  Article  CAS  Google Scholar 

  23. Sonoda H, Abe M, Sugimoto T, Sato Y, Bando M, Fukui E, et al. Prevalence of hepatitis E virus (HEV) Infection in wild boars and deer and genetic identification of a genotype 3 HEV from a boar in Japan. J Clin Microbiol. 2004;42:5371–4.

    PubMed  Article  Google Scholar 

  24. Nishizawa T, Takahashi M, Endo K, Fujiwara S, Sakuma N, Kawazuma F, et al. Analysis of the full-length genome of hepatitis E virus isolates obtained from wild boars in Japan. J Gen Virol. 2005;86:3321–6.

    PubMed  Article  CAS  Google Scholar 

  25. Nakamura M, Takahashi K, Taira K, Taira M, Ohno A, Sakugawa H, et al. Hepatitis E virus infection in wild mongooses of Okinawa, Japan: Demonstration of anti-HEV antibodies and a full-genome nucleotide sequence. Hepatol Res. 2006;34:137–40.

    PubMed  Article  CAS  Google Scholar 

  26. Tanaka E, Matsumoto A, Takeda N, Li TC, Umemura T, Yoshizawa K, et al. Age-specific antibody to hepatitis E virus has remained constant during the past 20 years in Japan. J Viral Hepat. 2005;12:439–42.

    PubMed  Article  CAS  Google Scholar 

  27. Fukuda S, Ishikawa M, Ochiai N, Suzuki Y, Sunaga J, Shinohara N, et al. Unchanged high prevalence of antibodies to hepatitis E virus (HEV) and HEV RNA among blood donors with an elevated alanine aminotransferase level in Japan during 1991–2006. Arch Virol. 2007;152:1623–35.

    PubMed  Article  CAS  Google Scholar 

  28. Mizuo H, Suzuki K, Takikawa Y, Sugai Y, Tokita H, Akahane 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.

    PubMed  Article  Google Scholar 

  29. Takahashi M, Kusakai S, Mizuo H, Suzuki K, Fujimura K, Masuko K, 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.

    PubMed  Article  CAS  Google Scholar 

  30. Gotanda Y, Iwata A, Ohnuma H, Yoshikawa A, Mizoguchi H, Endo K, et al. Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan. J Med Virol. 2007;79:734–42.

    PubMed  Article  CAS  Google Scholar 

  31. Inoue J, Takahashi M, Yazaki Y, Tsuda F, Okamoto H. Development and validation of an improved RT-PCR assay with nested universal primers for detection of hepatitis E virus strains with significant sequence divergence. J Virol Methods. 2006;137:325–33.

    PubMed  Article  CAS  Google Scholar 

  32. Ina Y. ODEN: a program package for molecular evolutionary analysis and database search of DNA and amino acid sequences. Comput Appl Biosci. 1994;10:11–2.

    PubMed  CAS  Google Scholar 

  33. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–80.

    PubMed  Article  CAS  Google Scholar 

  34. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987;4:406–25.

    PubMed  CAS  Google Scholar 

  35. Felsenstein J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution. 1985;39:783–91.

    Article  Google Scholar 

  36. Nagasaki F, Ueno Y, Kanno N, Okamoto H, Shimosegawa T. A case of acute hepatitis with positive autoantibodies who actually had hepatitis E virus infection. Hepatol Res. 2005;32:134–7.

    PubMed  Article  Google Scholar 

  37. Nagasaki F, Ueno Y, Mano Y, Igarashi T, Yahagi K, Niitsuma H, et al. A patient with clinical features of acute hepatitis E viral infection and autoimmune hepatitis. Tohoku J Exp Med. 2005;206:173–9.

    PubMed  Article  Google Scholar 

  38. Mizuo H, Yazaki Y, Sugawara K, Tsuda F, Takahashi M, Nishizawa T, 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.

    PubMed  Article  CAS  Google Scholar 

  39. Abe T, Aikawa T, Akahane Y, Arai M, Asahina Y, Atarashi Y, et al. Demographic, epidemiological, and virological characteristics of hepatitis E virus infections in Japan based on 254 human cases collected nationwide (in Japanese with English abstract). Kanzo. 2006;47:384–91.

    Article  Google Scholar 

  40. Yamamoto T, Suzuki H, Toyota T, Takahashi M, Okamoto H. Three male patients with sporadic acute hepatitis E in Sendai, Japan, who were domestically infected with hepatitis E virus of genotype III or IV. J Gastroenterol. 2004;39:292–8.

    PubMed  Article  Google Scholar 

  41. Takahashi K, Kang JH, Ohnishi S, Hino K, Mishiro S. Genetic heterogeneity of hepatitis E virus recovered from Japanese patients with acute sporadic hepatitis. J Infect Dis. 2002;185:1342–5.

    PubMed  Article  CAS  Google Scholar 

  42. Sainokami S, Abe K, Kumagai I, Miyasaka A, Endo R, Takikawa Y, et al. Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A. J Gastroenterol. 2004;39:640–8.

    PubMed  Article  Google Scholar 

  43. Suzuki K, Aikawa T, Okamoto H. Fulminant hepatitis E in Japan. N Engl J Med. 2002;347:1456.

    PubMed  Article  Google Scholar 

  44. Ohnishi S, Kang JH, Maekubo H, Takahashi K, Mishiro S. A case report: two patients with fulminant hepatitis E in Hokkaido, Japan. Hepatol Res. 2003;25:213–8.

    PubMed  Article  Google Scholar 

  45. Takahashi K, Kang JH, Ohnishi S, Hino K, Miyakawa H, Miyakawa Y, et al. Full-length sequences of six hepatitis E virus isolates of genotypes III and IV from patients with sporadic acute or fulminant hepatitis in Japan. Intervirology. 2003;46:308–18.

    PubMed  Article  CAS  Google Scholar 

  46. Inoue J, Nishizawa T, Takahashi M, Aikawa T, Mizuo H, Suzuki K, et al. Analysis of the full-length genome of genotype 4 hepatitis E virus isolates from patients with fulminant or acute self-limited hepatitis E. J Med Virol. 2006;78:476–84.

    PubMed  Article  CAS  Google Scholar 

  47. Yajima Y, Takahashi N, Yamagishi H, Kodama A, Miyazaki A, Sugiyama K, et al. An acute hepatitis case domestically infected with a hepatitis E virus whose nucleotide sequence showed a high similarity to that from a domestic swine in Japan (in Japanese). Nippon Shokakibyo Gakkai Zasshi (Jpn J Gastroenterol). 2003;100:454–8.

    Google Scholar 

  48. Takikawa Y, Yasumi Y, Sato A, Endo R, Suzuki K, Mori Y, et al. A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation. Hepatol Res. 2007;37:158–65.

    PubMed  CAS  Google Scholar 

  49. Shapiro CN, Margolis HS. Worldwide epidemiology of hepatitis A virus infection. J Hepatol. 1993;18(Suppl 2):S11–4.

    PubMed  Article  Google Scholar 

  50. Melnick JL. History and epidemiology of hepatitis A virus. J Infect Dis. 1995;171(Suppl 1):S2–8.

    PubMed  Google Scholar 

  51. Sagnelli E, Rossi G, Coppola N, Scolastico C, Onofrio M, Filippini P, et al. Antibodies to hepatitis A virus in Italian patients with chronic liver disease. Epidemiol Infect. 2001;127:341–6.

    PubMed  Article  CAS  Google Scholar 

  52. Masuda J, Yano K, Tamada Y, Takii Y, Ito M, Omagari K, et al. Acute hepatitis E of a man who consumed wild boar meat prior to the onset of illness in Nagasaki, Japan. Hepatol Res. 2005;31:178–83.

    PubMed  Article  Google Scholar 

  53. Matsubayashi K, Nagaoka Y, Sakata H, Sato S, Fukai K, Kato T, et al. Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion. 2004;44:934–40.

    PubMed  Article  Google Scholar 

  54. Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, 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.

    PubMed  Article  CAS  Google Scholar 

  55. Ohnishi S, Kang JH, Maekubo H, Arakawa T, Karino Y, Toyota J, et al. Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan. Hepatol Res. 2006;36:301–7.

    PubMed  Article  Google Scholar 

  56. Fan ZP, Lin SH, Cai SP, Ji YJ, Gao F, Zhang HY, et al. An analysis of the clinical characteristics of patients with chronic hepatitis B superinfected with acute hepatitis E (in Chinese with English abstract). Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2007;21:325–7.

    PubMed  CAS  Google Scholar 

  57. Kumar M, Sharma BC, Sarin SK. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease. J Gastroenterol Hepatol. 2008;23:883–7.

    PubMed  Article  Google Scholar 

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Acknowledgments

This study was supported in part by grants from the Ministry of Health, Labor and Welfare in Japan, and the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Affiliations

  1. Division of Gastroenterology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan

    Jun Inoue, Yoshiyuki Ueno, Koji Fukushima, Takayuki Kogure, Yasuteru Kondo, Eiji Kakazu, Keiichi Tamai, Osamu Kido, Yu Nakagome, Masashi Ninomiya, Noriyuki Obara, Yuta Wakui & Tooru Shimosegawa

  2. Department of Gastroenterology, Sendai City Hospital, Sendai, Japan

    Futoshi Nagasaki

  3. Department of Gastroenterology, Ishinomaki Municipal Hospital, Ishinomaki, Miyagi, Japan

    Takehiro Akahane

  4. Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan

    Masaharu Takahashi & Hiroaki Okamoto

Authors
  1. Jun Inoue
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  2. Yoshiyuki Ueno
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  3. Futoshi Nagasaki
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  4. Takehiro Akahane
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  5. Koji Fukushima
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  6. Takayuki Kogure
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  7. Yasuteru Kondo
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  8. Eiji Kakazu
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  9. Keiichi Tamai
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  10. Osamu Kido
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  11. Yu Nakagome
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  12. Masashi Ninomiya
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  13. Noriyuki Obara
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  14. Yuta Wakui
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  15. Masaharu Takahashi
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  16. Hiroaki Okamoto
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  17. Tooru Shimosegawa
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Corresponding author

Correspondence to Yoshiyuki Ueno.

Additional information

The nucleotide sequence data reported in this study have been assigned GenBank/EMBL/DDBJ accession numbers AB206467 and AB453332–AB453337.

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Inoue, J., Ueno, Y., Nagasaki, F. et al. Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan. J Gastroenterol 44, 329–337 (2009). https://doi.org/10.1007/s00535-009-0012-3

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  • DOI: https://doi.org/10.1007/s00535-009-0012-3

Keywords

  • Hepatitis E virus
  • HEV
  • Phylogenetic analysis
  • Miyagi
  • Tohoku