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Published in: European Journal of Pediatrics 7/2010

01-07-2010 | Short Report

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

Authors: Masataka Ishimura, Shouichi Ohga, Masako Ichiyama, Koichi Kusuhara, Hidetoshi Takada, Toshiro Hara, Masaharu Takahashi, Hiroaki Okamoto

Published in: European Journal of Pediatrics | Issue 7/2010

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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.
Literature
1.
go back to reference Adachi Y, Yasui H, Yuasa H et al (2002) Hepatitis B virus-associated aplastic anemia followed by myelodysplastic syndrome. Am J Med 112:330–332CrossRefPubMed Adachi Y, Yasui H, Yuasa H et al (2002) Hepatitis B virus-associated aplastic anemia followed by myelodysplastic syndrome. Am J Med 112:330–332CrossRefPubMed
2.
go back to reference Brown KE, Tisdale J, Barrett AJ et al (1997) Hepatitis-associated aplastic anemia. N Engl J Med 336:1059–1064CrossRefPubMed Brown KE, Tisdale J, Barrett AJ et al (1997) Hepatitis-associated aplastic anemia. N Engl J Med 336:1059–1064CrossRefPubMed
3.
go back to reference Desai M, Pal R, Deshmukh R, Banker D (2005) Replication of TT virus in hepatocyte and leucocyte cell lines. J Med Virol 77:136–143CrossRefPubMed Desai M, Pal R, Deshmukh R, Banker D (2005) Replication of TT virus in hepatocyte and leucocyte cell lines. J Med Virol 77:136–143CrossRefPubMed
4.
go back to reference de Smit MH, Noteborn MH (2009) Apoptosis-inducing proteins in chicken anemia virus and TT virus. Curr Top Microbiol Immunol 331:131–149CrossRefPubMed de Smit MH, Noteborn MH (2009) Apoptosis-inducing proteins in chicken anemia virus and TT virus. Curr Top Microbiol Immunol 331:131–149CrossRefPubMed
5.
go back to reference Domenech P, Palomeque A, Martinez-Gutierrez A, Vinolas N, Vela E, Jimenez R (1986) Severe aplastic anaemia following hepatitis A. Acta Haematol 76:227–229CrossRefPubMed Domenech P, Palomeque A, Martinez-Gutierrez A, Vinolas N, Vela E, Jimenez R (1986) Severe aplastic anaemia following hepatitis A. Acta Haematol 76:227–229CrossRefPubMed
7.
go back to reference Hu ZJ, Lang ZW, Zhou YS et al (2002) Clinicopathological study on TTV infection in hepatitis of unknown etiology. World J Gastroenterol 8:288–293PubMed Hu ZJ, Lang ZW, Zhou YS et al (2002) Clinicopathological study on TTV infection in hepatitis of unknown etiology. World J Gastroenterol 8:288–293PubMed
8.
go back to reference Imai T, Itoh S, Okada H, Onishi S (2002) Aplastic anemia following hepatitis associated with echovirus 3. Pediatr Int 44:522–524CrossRefPubMed Imai T, Itoh S, Okada H, Onishi S (2002) Aplastic anemia following hepatitis associated with echovirus 3. Pediatr Int 44:522–524CrossRefPubMed
9.
go back to reference 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 321:341–348CrossRefPubMed 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 321:341–348CrossRefPubMed
10.
go back to reference 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 61:165–170CrossRefPubMed 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 61:165–170CrossRefPubMed
11.
go back to reference Kojima S, Matsuyama K, Kodera Y, Okada J (1989) Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia. Br J Haematol 71:147–151CrossRefPubMed Kojima S, Matsuyama K, Kodera Y, Okada J (1989) Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia. Br J Haematol 71:147–151CrossRefPubMed
12.
go back to reference Lau YL, Srivastava G, Lee CW et al (1994) Epstein–Barr virus associated aplastic anaemia and hepatitis. J Paediatr Child Health 30:74–76CrossRefPubMed Lau YL, Srivastava G, Lee CW et al (1994) Epstein–Barr virus associated aplastic anaemia and hepatitis. J Paediatr Child Health 30:74–76CrossRefPubMed
13.
go back to reference Lim SH, Zhang Y, Wang Z et al (2004) Umbilical cord blood transplant in hepatitis C-associated severe aplastic anemia. Bone Marrow Transplant 33:565–567CrossRefPubMed Lim SH, Zhang Y, Wang Z et al (2004) Umbilical cord blood transplant in hepatitis C-associated severe aplastic anemia. Bone Marrow Transplant 33:565–567CrossRefPubMed
14.
go back to reference Miyamoto M, Takahashi H, Sakata I, Adachi Y (2000) Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection. Intern Med 39:1068–1070CrossRefPubMed Miyamoto M, Takahashi H, Sakata I, Adachi Y (2000) Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection. Intern Med 39:1068–1070CrossRefPubMed
15.
go back to reference 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 241:92–97CrossRefPubMed 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 241:92–97CrossRefPubMed
16.
go back to reference Okamoto H, Takahashi M, Nishizawa T et al (2000) Replicative forms of TT virus DNA in bone marrow cells. Biochem Biophys Res Commun 270:657–662CrossRefPubMed Okamoto H, Takahashi M, Nishizawa T et al (2000) Replicative forms of TT virus DNA in bone marrow cells. Biochem Biophys Res Commun 270:657–662CrossRefPubMed
17.
go back to reference Okamoto H (2009) History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol 331:1–20CrossRefPubMed Okamoto H (2009) History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol 331:1–20CrossRefPubMed
18.
go back to reference 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 279:700–707CrossRefPubMed 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 279:700–707CrossRefPubMed
19.
go back to reference 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 10:1–16CrossRef 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 10:1–16CrossRef
20.
go back to reference Osugi Y, Yagasaki H, Sako M et al (2007) Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia. Haematologica 92:1687–1690CrossRefPubMed Osugi Y, Yagasaki H, Sako M et al (2007) Antithymocyte globulin and cyclosporine for treatment of 44 children with hepatitis associated aplastic anemia. Haematologica 92:1687–1690CrossRefPubMed
21.
go back to reference 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 93:468–470CrossRefPubMed 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 93:468–470CrossRefPubMed
22.
go back to reference 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 27:183–190CrossRefPubMed 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 27:183–190CrossRefPubMed
23.
go back to reference Tajiri H, Tanaka T, Sawada A et al (2001) Three cases with TT virus infection and idiopathic neonatal hepatitis. Intervirology 44:364–369CrossRefPubMed Tajiri H, Tanaka T, Sawada A et al (2001) Three cases with TT virus infection and idiopathic neonatal hepatitis. Intervirology 44:364–369CrossRefPubMed
24.
go back to reference 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 67:501–509CrossRefPubMed 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 67:501–509CrossRefPubMed
25.
go back to reference 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 20:288–300CrossRefPubMed 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 20:288–300CrossRefPubMed
26.
go back to reference Tsuda F, Takahashi M, Nishizawa T et al (2001) IgM-class antibodies to TT virus (TTV) in patients with acute TTV infection. Hepatol Res 19:1–11CrossRefPubMed Tsuda F, Takahashi M, Nishizawa T et al (2001) IgM-class antibodies to TT virus (TTV) in patients with acute TTV infection. Hepatol Res 19:1–11CrossRefPubMed
27.
go back to reference Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519CrossRefPubMed Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519CrossRefPubMed
28.
Metadata
Title
Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus
Authors
Masataka Ishimura
Shouichi Ohga
Masako Ichiyama
Koichi Kusuhara
Hidetoshi Takada
Toshiro Hara
Masaharu Takahashi
Hiroaki Okamoto
Publication date
01-07-2010
Publisher
Springer-Verlag
Published in
European Journal of Pediatrics / Issue 7/2010
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-009-1116-8

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