Skip to main content

Advertisement

Log in

Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus

  • Short Report
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

A 12-year-old Japanese boy suffered from severe acute hepatitis and pancytopenia. The patient underwent successful bone marrow transplantation from an HLA-identical sister. Torque teno virus (TTV) DNA of genotype 1a and IgM-class antibody against the virus were detected in sera at the onset of hepatitis. TTV/1a DNA and anti-TTV/1a IgM antibody levels were undetectable on the 16th and 46th days after the onset of illness, respectively. Anti-TTV/1a IgG antibody was positive throughout the observation period. Sequential viral load and anti-TTV/1a IgM antibody suggested a primary infection of TTV/1a. Genomic sequence of the virus coincided with that of the original strain first isolated from human. TTV DNA was quantified at 130 copies in 105 bone marrow mononuclear cells, which suggested that infection of hematopoietic cells might be the cause of aplasia. This is the first report of TTV hepatitis-associated aplastic anemia assessed by the anti-TTV antibodies and viral load in peripheral blood and bone marrow.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Abbreviations

AA:

Aplastic anemia

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

BM:

Bone marrow

BMT:

Bone marrow transplantation

EBV:

Epstein–Barr virus

HAA:

Hepatitis-associated aplastic anemia

MNC:

Mononuclear cells

PCR:

Polymerase chain reaction

PB:

Peripheral blood

rr:

Reference range

SAA:

Severe aplastic anemia

TTV:

Torque teno virus

TB:

Total bilirubin

References

  1. Adachi Y, Yasui H, Yuasa H et al (2002) Hepatitis B virus-associated aplastic anemia followed by myelodysplastic syndrome. Am J Med 112:330–332

    Article  PubMed  Google Scholar 

  2. Brown KE, Tisdale J, Barrett AJ et al (1997) Hepatitis-associated aplastic anemia. N Engl J Med 336:1059–1064

    Article  CAS  PubMed  Google Scholar 

  3. Desai M, Pal R, Deshmukh R, Banker D (2005) Replication of TT virus in hepatocyte and leucocyte cell lines. J Med Virol 77:136–143

    Article  CAS  PubMed  Google Scholar 

  4. de Smit MH, Noteborn MH (2009) Apoptosis-inducing proteins in chicken anemia virus and TT virus. Curr Top Microbiol Immunol 331:131–149

    Article  PubMed  Google Scholar 

  5. Domenech P, Palomeque A, Martinez-Gutierrez A, Vinolas N, Vela E, Jimenez R (1986) Severe aplastic anaemia following hepatitis A. Acta Haematol 76:227–229

    Article  CAS  PubMed  Google Scholar 

  6. Hino S, Miyata H (2007) Torque teno virus (TTV): current status. Rev Med Virol 17:45–57

    Article  CAS  PubMed  Google Scholar 

  7. Hu ZJ, Lang ZW, Zhou YS et al (2002) Clinicopathological study on TTV infection in hepatitis of unknown etiology. World J Gastroenterol 8:288–293

    CAS  PubMed  Google Scholar 

  8. Imai T, Itoh S, Okada H, Onishi S (2002) Aplastic anemia following hepatitis associated with echovirus 3. Pediatr Int 44:522–524

    Article  PubMed  Google Scholar 

  9. Kamada K, Kamahora T, Kabat P, Hino S (2004) Transcriptional regulation of TT virus: promoter and enhancer regions in the 1.2-kb noncoding region. Virology 321:341–348

    Article  CAS  PubMed  Google Scholar 

  10. Kikuchi K, Miyakawa H, Abe K et al (2000) Indirect evidence of TTV replication in bone marrow cells, but not in hepatocytes, of a subacute hepatitis/aplastic anemia patient. J Med Virol 61:165–170

    Article  CAS  PubMed  Google Scholar 

  11. Kojima S, Matsuyama K, Kodera Y, Okada J (1989) Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia. Br J Haematol 71:147–151

    Article  CAS  PubMed  Google Scholar 

  12. Lau YL, Srivastava G, Lee CW et al (1994) Epstein–Barr virus associated aplastic anaemia and hepatitis. J Paediatr Child Health 30:74–76

    Article  CAS  PubMed  Google Scholar 

  13. Lim SH, Zhang Y, Wang Z et al (2004) Umbilical cord blood transplant in hepatitis C-associated severe aplastic anemia. Bone Marrow Transplant 33:565–567

    Article  CAS  PubMed  Google Scholar 

  14. Miyamoto M, Takahashi H, Sakata I, Adachi Y (2000) Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection. Intern Med 39:1068–1070

    Article  CAS  PubMed  Google Scholar 

  15. Nishizawa T, Okamoto H, Konishi K et al (1997) A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 241:92–97

    Article  CAS  PubMed  Google Scholar 

  16. Okamoto H, Takahashi M, Nishizawa T et al (2000) Replicative forms of TT virus DNA in bone marrow cells. Biochem Biophys Res Commun 270:657–662

    Article  CAS  PubMed  Google Scholar 

  17. Okamoto H (2009) History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol 331:1–20

    Article  CAS  PubMed  Google Scholar 

  18. Okamoto H, Nishizawa T, Tawara A et al (2000) TT virus mRNAs detected in the bone marrow cells from an infected individual. Biochem Biophys Res Commun 279:700–707

    Article  CAS  PubMed  Google Scholar 

  19. Okamoto H, Nishizawa T, Kato N et al (1998) Molecular cloning and characterization of a novel DNA virus (TTV) associated with posttransfusion hepatitis of unknown etiology. Hepatol Res 10:1–16

    Article  Google Scholar 

  20. Osugi Y, Yagasaki H, Sako M et al (2007) Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia. Haematologica 92:1687–1690

    Article  CAS  PubMed  Google Scholar 

  21. Pardi DS, Romero Y, Mertz LE, Douglas DD (1998) Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature. Am J Gastroenterol 93:468–470

    Article  CAS  PubMed  Google Scholar 

  22. Safadi R, Or R, Ilan Y et al (2001) Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation. Bone Marrow Transplant 27:183–190

    Article  CAS  PubMed  Google Scholar 

  23. Tajiri H, Tanaka T, Sawada A et al (2001) Three cases with TT virus infection and idiopathic neonatal hepatitis. Intervirology 44:364–369

    Article  CAS  PubMed  Google Scholar 

  24. Tokita H, Murai S, Kamitsukasa H et al (2002) High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. J Med Virol 67:501–509

    Article  PubMed  Google Scholar 

  25. Tokita H, Murai S, Kamitsukasa H et al (2001) Influence of TT virus infection on the thrombocytopenia of patients with chronic liver disease. Hepatol Res 20:288–300

    Article  PubMed  Google Scholar 

  26. Tsuda F, Takahashi M, Nishizawa T et al (2001) IgM-class antibodies to TT virus (TTV) in patients with acute TTV infection. Hepatol Res 19:1–11

    Article  CAS  PubMed  Google Scholar 

  27. Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519

    Article  CAS  PubMed  Google Scholar 

  28. Zaidi Y, Chapman CS, Myint S (1996) Aplastic anaemia after HGV infection. Lancet 348:471–472

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Drs. Takahashi S and Suga N (Div. Pediatr., Beppu Nat. Hosp. Med. Cent., Oita, Japan) for collecting samples and Dr. Nomura A (Dept. Pediatr., Grad. Sch. Med. Sci., Kyushu Univ., Fukuoka, Japan) for the clinical support.

Financial support

This work was supported in part by a Grant-in-Aid for Scientific Research (C) to Ohga S from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Potential conflicts of interest

All authors have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shouichi Ohga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishimura, M., Ohga, S., Ichiyama, M. et al. Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus. Eur J Pediatr 169, 899–902 (2010). https://doi.org/10.1007/s00431-009-1116-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-009-1116-8

Keywords

Navigation