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Digestive Diseases and Sciences

, Volume 52, Issue 9, pp 2438–2443 | Cite as

Hepatitis Associated with Aplastic Anemia: Do CD8(+) Kupffer Cells Have a Role in the Pathogenesis?

  • Cem CengizEmail author
  • Nesrin Turhan
  • O. Faruk Yolcu
  • Sevinc Yılmaz
Case Report

Introduction

Hepatitis-associated aplastic anemia (HAAA), first described by Lorenz and Quaiser in 1955 [1], is a rare phenomenon which usually affects adolescents and young men [2] and is more common in the East than in the West [3, 4, 5]. It represents a minor proportion of all aplastic anemia cases [6] and may occur in 28% of young adults after liver transplantation for non-A, non-B hepatitis [7]. Although a limited number of aplastic anemia cases have been reported in association with hepatitis A, B, and G, parvovirus B19, Epstein-Barr virus (EBV), transfusion transmitted virus (TTV), and echovirus [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20], the causative agent in most of the cases still remains unknown [21, 23]. Patients typically develop severe aplastic anemia 2 to 3 months after an episode of acute hepatitis. Aplastic anemia is always fatal if untreated [2, 11] and the hepatitis associated with this may be mild and transient [2, 22], fulminant [7, 23], or chronic [2]....

Keywords

Hepatitis Aplastic anemia Cytotoxic T cells Kupffer cells Immunohistochemistry Immunosuppressive therapy 

References

  1. 1.
    Lorenz E, Quaiser K (1955) Panmyelopathie nach Hepatitis epidemica. Wien Med Wochenschr 105:19–22PubMedGoogle Scholar
  2. 2.
    Hagler L, Pastore RA, Bergin JJ, Wrensch MR (1975) Aplastic anemia following viral hepatitis: Report of two fatal cases and literature review. Medicine 54:139–164PubMedCrossRefGoogle Scholar
  3. 3.
    Young NS, Issaragrisil S, Chen WC, Takaku F (1986) Aplastic anemia in the Orient. Br J Haematol 62:1–6PubMedGoogle Scholar
  4. 4.
    Issaragrisil S, Sriratanasatavorn C, Piankijagum A, et al. (1991) The incidence of aplastic anemia in Bangkok. Blood 77:2166–2168PubMedGoogle Scholar
  5. 5.
    Kaufman DW, Kelly JP, Levy M, Shapiro S (1991) The drug etiology of agranulocytosis and aplastic anemia. Oxford University Press, New YorkGoogle Scholar
  6. 6.
    Young NS (1994) Viruses as agents of marrow failure. In: Young NS, Alter BP (eds) Aplastic anemia, acquired and inherited. Saunders, Philadelphia, pp 133–158Google Scholar
  7. 7.
    Tzakis AG, Arditi M, Whitington PF, et al. (1988) Aplastic anemia complicating orthotopic liver transplantation for non-A, non-B hepatitis. N Engl J Med 319:393–396PubMedCrossRefGoogle Scholar
  8. 8.
    Smith D, Gribble TJ, Yeager AS, et al. (1978) Spontaneous resolution of severe aplastic anemia associated with viral hepatitis A in a 6 year old child. Am J Hematol 5:247–252PubMedCrossRefGoogle Scholar
  9. 9.
    Domenech P, Palomeque A, Martinez-Gutierrez A, et al. (1986) Severe aplastic anemia following hepatitis A. Acta Haematol 76:227–229PubMedCrossRefGoogle Scholar
  10. 10.
    Casciato DA, Klein CA, Kaplowitz N, Scott JL (1978) Aplastic anemia associated with type B viral hepatitis. Arch Intern Med 138:1557–1558PubMedCrossRefGoogle Scholar
  11. 11.
    McSweeney PA, Carter JM, Green GJ, Romeril KR (1988) Fatal aplastic anemia associated with hepatitis B viral infection. Am J Med 85:255–256PubMedCrossRefGoogle Scholar
  12. 12.
    Adachi Y, Yasui H, Yuasa H, Ishi Y, Imai K, Kato Y (2002) Hepatitis B virus-associated aplastic anemia followed by myelodysplastic syndrome. Am J Med 112:330–331PubMedCrossRefGoogle Scholar
  13. 13.
    Bozyaka H, Yurdaydin C, Toruner M, Arat M, Bozdayi AM, Erekul S, Cinar K, Koc H, Uzunalimoglu O (2002) Remission of severe aplastic anemia associated with hepatitis B virus infection after viral clearance: Potential role of lamivudine. Dig Dis Sci 47:1782–1785CrossRefGoogle Scholar
  14. 14.
    Zaidi Y, Chapman CS, Myint S (1996) Aplastic anemia after HGV infection. Lancet 348:471–472PubMedCrossRefGoogle Scholar
  15. 15.
    Byrnes JJ, Banks AT, Piatack M Jr, Kim JP (1996) Hepatitis G-associated aplastic anemia. Lancet 348:472PubMedCrossRefGoogle Scholar
  16. 16.
    Crespo J, de las Heras B, Rivero M, Lozano JL, Fabrega E, Pons-Romero F (1999) Hepatitis G virus infection as a possible causative agent of community-acquired hepatitis and associated aplastic anemia. Postgrad Med J 75:159–160PubMedGoogle Scholar
  17. 17.
    Pardi DS, Romero Y, Mertz LE, Dougles 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 93:468–470PubMedCrossRefGoogle Scholar
  18. 18.
    Lau YL, Srivastava G, Lee CW, Kwong KY, Yeung CY (1994) Epstein-Barr virus associated aplastic anemia and hepatitis. J Paediatr Child Health 30:74–76PubMedGoogle Scholar
  19. 19.
    Poovorawan Y, Tangkijvanich P, Theamboonlers A, Hirsch P (2001) Transfusion transmissible virus TTV and its putative role in the etiology of liver disease. Hepatogastroenterology 48:256–260PubMedGoogle Scholar
  20. 20.
    Imai T, Itoh S, Okada H, Onishi S (2002) Aplastic anemia following hepatitis associated with echovirus 3. Pediatr Int 44:522–524PubMedCrossRefGoogle Scholar
  21. 21.
    Safadi R, Or R, Ilan Y, Naparstek E, Nagler A, Klein A, Ketzinel-Gilaad M, Ergunay K, Danon D, Shouval D, Galun E (2001) Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation. Bone Marrow Transplant 27:183–190PubMedCrossRefGoogle Scholar
  22. 22.
    Bottinger LE, Westerholm B (1972) Aplastic anemia. III. Aplastic anemia and infectious hepatitis. Acta Med Scand 192:323–326Google Scholar
  23. 23.
    Langnas AN, Markin RS, Cattral MS, et al. (1995) Parvovirus B19 as a possible causative agent of fulminant liver failure and associated aplastic anemia. Hepatology 22:1661–1665PubMedGoogle Scholar
  24. 24.
    Brown KE, Tisdale J, Barrett J, Dunbar CE, Young NS (1997) Hepatitis-associated aplastic anemia. N Engl J Med 336:1059–1064PubMedCrossRefGoogle Scholar
  25. 25.
    Tang TJ, Kwekkeboom J, Laman JD, et al. (2003) The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. J Viral Hepat 10:159–167PubMedCrossRefGoogle Scholar
  26. 26.
    Schroeter M, Stoll G, Weissert R, Hartung HP, Lassmann H, Jander S (2003) CD8+ phagocyte recruitment in rat experimental autoimmune encephalomyelitis: Association with inflammatory tissue destruction. Am J Pathol 163:1517–1524PubMedGoogle Scholar
  27. 27.
    Baba T, İshizu A, Iwasaki S, Suzuki A, Tomaru U, Ikeda H, Yoshiki T, Kasahara M (2005) CD4/CD8 double-positive macrophages infiltrating at inflammatory sites: A population of monocytes/macrophages with a cytotoxic phenotype. Blood, 2006 Mar 1; 107(5): 2004--12.Google Scholar
  28. 28.
    Kayashima S, Kondou T, Watanabe Y, Kobari S, Kagari M (1998) A patient with non-A, non-B, non-C hepatitis-associated aplastic anemia recovered promptly following immuno-suppressive thrapy, including antithymocyte globulin. Int J Hematol 67:403–409PubMedCrossRefGoogle Scholar
  29. 29.
    Adachi Y, Usuki K, Kazama H, Iki S, Matsuya S, Urabe A (2001) Successful combined therapy with ATG, cyclosporine and G-CSF for both liver dysfunction and bone marrow failure in hepatitis-associated aplastic anemia. Rinsho Ketsueki 42:691–695PubMedGoogle Scholar
  30. 30.
    Kagan WA, Ascensao JA, Pahwa RN, et al. (1976) Aplastic anemia: Presence in human bone marrow of cells that suppress myelopoiesis. Proc Natl Acad Sci USA 73:2890–2894PubMedCrossRefGoogle Scholar
  31. 31.
    Maciejewski JP, Hibbs JR, Anderson S, Katevas P, Young NS (1994) Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure. Exp Hematol 22:1102–1110PubMedGoogle Scholar
  32. 32.
    Nisticó A, Young NS (1994) Gamma-interferon gene expression in the bone marrow of patients with aplastic anemia. Ann Intern Med 120:463–469PubMedGoogle Scholar
  33. 33.
    Rehermann B (2003) Immune responses in hepatitis B virus infection. Semin Liver Dis 23:21–38PubMedCrossRefGoogle Scholar
  34. 34.
    Mizukoshi E, Rehermann B (2001) Immune responses and immunity in hepatitis C virus infection. J Gastroenterol 36:799–808PubMedCrossRefGoogle Scholar
  35. 35.
    Bowen DG, Warren A, Davis T, Hoffmann MW, McCaughan GW, De St Groth BF, Bertolino P (2002) Cytokine-dependent bystander hepatitis due to intrahepatic murine CD8 T-cell activation by bone marrow-derived cells. Gastroenterology 123:1252–1264PubMedCrossRefGoogle Scholar
  36. 36.
    Champlin RE, Horowitz MM, Van Bekkum DW, et al. (1989) Graft failure following bone marrow transplantation for severe aplastic anemia: Risk factors and treatment results. Blood 73:606–613PubMedGoogle Scholar
  37. 37.
    May WS, Sensenbrenner LL, Burns WH, et al. (1993) BMT for severe aplastic anemia using cyclosporine. Bone Marrow Transplant 11:459–464PubMedGoogle Scholar
  38. 38.
    Storb R, Etzioni R, Claudio A, et al. (1994) Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia. Blood 84:941–949PubMedGoogle Scholar
  39. 39.
    Camitta BM, Nathan DG, Forman EN, Parman R, Rappeport JM, Orellana TD (1974) Posthepatic severe aplastic anemia—an indication for early bone marrow transplantation. Blood 43:473–483PubMedGoogle Scholar
  40. 40.
    Gluckman E, Devergie A, Faille A, Bussel A, Benbunan M, Bernard J (1979) Antilymphocyte globulin treatment in severe aplastic anemia-comparison with bone marrow transplantation: Report of 60 cases. Haematol Blut-transfus 24:171–179Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Cem Cengiz
    • 1
    Email author
  • Nesrin Turhan
    • 2
  • O. Faruk Yolcu
    • 1
  • Sevinc Yılmaz
    • 3
  1. 1.Department of GastroenterologyTurkiye Yuksek Ihtisas HastanesiEmekTurkey
  2. 2.Department of PathologyTurkiye Yuksek Ihtisas HastanesiAnkaraTurkey
  3. 3.Department of HematologyTurkiye Yuksek Ihtisas HastanesiAnkaraTurkey

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