Digestive Diseases and Sciences

, Volume 40, Issue 4, pp 763–773 | Cite as

Posttransfusional, LKM-1-autoantibody-positive hepatitis C virus infection, cryoglobulinemia, and aplastic anemia

  • Malte Peters
  • Martin Trippler
  • Hanns Löhr
  • Werner Gödderz
  • Wolfgang Herr
  • Stefan Störkel
  • Karl-Hermann Meyer Zum Büschenfelde
  • Guido Gerken
Case Report

Key words

hepatitis C virus autoimmunity polymerase chain reaction minus-stranded HCV-RNA cryoglobulinemia LKM-1 autoantibodies posttransfusional hepatitis 


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  1. 1.
    Rao KRP, Patel AR, Anderson MJ, Hodgson J, Jones SE, Pattison JR: Infection with parvovirus-like virus and aplastic crisis in chronic hemolytic anemia. Ann Intern Med 98:930–932, 1983PubMedGoogle Scholar
  2. 2.
    Young N, Harrison M, Moore J, Mortimer P, Humphries RK: Direct demonstration of the human parvovirus in erythroid progenitor cells infectedin vitro. J Clin Invest 74:2024–2032, 1984PubMedGoogle Scholar
  3. 3.
    Young N, Mortimer P: Viruses and bone marrow failure. Blood 64:729–737, 1984Google Scholar
  4. 4.
    Wilson HA, McLaren GD, Dworken HJ, Tebbi K: Transient pure red-cell aplasia: Cell-mediated suppression of erythropoiesis associated with hepatitis. Ann Intern Med 92:196–198, 1980PubMedGoogle Scholar
  5. 5.
    Zeldis JB, Dienstag JL, Gale PR: Aplastic anemia and non-A, non-B hepatitis. Am J Med 74:64–68, 1983Google Scholar
  6. 6.
    Perrillo RP, Pohl DA, Roodman ST, Tsai CC: Acute non-A, non-B hepatitis with serum sickness-like syndrome and aplastic anemia. JAMA 245:494–496, 1981PubMedGoogle Scholar
  7. 7.
    Cargnel A, Vigano P, Davoli C, Morelli R, Perna MC, Mariscotti C: Sporadic acute non-A non-B hepatitis complicated by aplastic anemia. Am J Gastroenterol 78:245–247, 1983PubMedGoogle Scholar
  8. 8.
    Tzakis AG, Arditi M, Whitington PF, Yanaga K, Esquivel C, Andrews WA, Makowka L, Malatak L, Malatak J, Freese DK, Stock PG, Ascher NL, Johnsson FL, Broelsch CE, Starzl TE: Aplastic anemia complicating orthotopic liver transplantation for non-A, non-B hepatitis. N Engl J Med 319:393–396, 1988PubMedGoogle Scholar
  9. 9.
    Foon KA, Mitsuyasu RT, Schroff RW, McIntyre RE, Champlin R, Gale RP: Immunologic defects in young male patients with hepatitis-associated aplastic anemia. Ann Intern Med 100:657–662, 1984PubMedGoogle Scholar
  10. 10.
    Zoumbos NC, Djeu JY, Young NS: Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytesin vitro. J Immunol 133:769–774, 1984PubMedGoogle Scholar
  11. 11.
    Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS: Circulating activating suppressor T lymphocytes in aplastic anemia. N Engl J Med 312:257–265, 1985PubMedGoogle Scholar
  12. 12.
    Gascon P, Zoumbos NC, Scala G, Djeu JY, Moore JG, Young NS: Lymphokine abnormalities in aplastic anemia: Implications for the mechanisms of action of antithymocyte globulin. Blood 65:407–413, 1985PubMedGoogle Scholar
  13. 13.
    Zoumbos N, Gascon P, Djeu J, Young N: Interferon is a mediator of hematopoeitic suppression in aplastic anemiain vitro and possiblyin vivo. Proc Natl Acad Sci USA 82:188–192, 1985PubMedGoogle Scholar
  14. 14.
    Herrmann F, Griffin JD, Meuer SG, Meyer zum Büschenfelde KH: Establishment of an interleukin 2-dependent T cell line derived from a patient with severe aplastic anemia, which inhibitsin vitro hematopoiesis. J Immunol 136:1629–1634, 1986PubMedGoogle Scholar
  15. 15.
    Nisticò A, Young NS: Gamma-interferon gene expression in the bone marrow of patients with aplastic anemia. Ann Intern Med 120:643–649, 1994Google Scholar
  16. 16.
    Goergen B, Jakobs S, Symmons P, Hornes E, Meyer zum Büschenfelde KH, Gerken G: Quantitation of HCV-replication using one-step competitive RT-PCR and a solid phase, colorimetric detection method. J Hepatol 21:678–682; 1994PubMedGoogle Scholar
  17. 17.
    Féray C, Samuel D, Thiers V, Gigon M, Pichau F, Bismuth A, Reynes M, Maisonneuve P, Bismuth H, Bréchot C: Reinfection of liver graft by hepatitis C virus after liver transplantation. J Clin Invest 89:1361–1365, 1992PubMedGoogle Scholar
  18. 18.
    Zaaijer HL, Cuypers HTM, Reesink HW, Winkel IN, Gerken G, Lelie PN: Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet 341:722–724, 1993PubMedGoogle Scholar
  19. 19.
    Fong TL, Shindo M, Feinstone SM, Hoofnagle JH, Di Bisceglie AM: Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C. J Clin Invest 88:1058–1060, 1991PubMedGoogle Scholar
  20. 20.
    Takehara T, Hayashi N, Mita E, Hagiwara H, Ueda K, Katayama K, Kasahara A, Fusamoto H, Kamada T: Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction: Implication for hepatitis C virus replication in infected tissue. Hepatology 15:387–390, 1992PubMedGoogle Scholar
  21. 21.
    Wang JT, Sheu JC, Lin JT, Wang TH, Chen DS: Detection of replicative forms of hepatitis C virus RNA in peripheral blood mononuclear cells. J Infect Dis 166:1167–1169, 1992PubMedGoogle Scholar
  22. 22.
    Miltenyi S, Müller W, Weichel W, Radbruch A: High gradient magnetic cell separation with MACS. Cytometry 11:231–238, 1990PubMedGoogle Scholar
  23. 23.
    Simmonds P, McOrnish F, Yap PL, Chan SW, Lin CK, Dusheiko G, Saeed AA, Holmes EC: Sequence variability in the 5′ non-coding region of hepatitis C virus: Identification of a new virus type and restrictions on sequence diversity. J Gen Virol 74:661–668, 1993PubMedGoogle Scholar
  24. 24.
    Stuyver L, Rossau R, Wyseur A, Duhamel M, Vanderborght B, van Heuverswyn H, Maertens G: Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol 74:1105–1113, 1993Google Scholar
  25. 25.
    Manns M, Meyer zum Büschenfelde KH, Slusarszyk J, Dienes HP: Detection of liver-kidney microsomal autoantibodies by radioimmunoassay and their relation to antimitochandrial antibodies in inflammatory liver diseases. Clin Exp Immunol 57:600–608, 1984PubMedGoogle Scholar
  26. 26.
    Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Büschenfelde KH: Characterization of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1:292–294, 1987PubMedGoogle Scholar
  27. 27.
    Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF: Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J Clin Invest 83:1066–1072, 1989PubMedGoogle Scholar
  28. 28.
    Treichel U, Poralla T, Hess G, Manns M, Meyer zum Büschenfelde KH: Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology 11:606–612, 1990PubMedGoogle Scholar
  29. 29.
    Michel G, Ritter A, Gerken G, Meyer zum Büschenfelde KH, Decker R, Manns MP: Anti-GOR and hepatitis C virus in autoimmune liver diseases. Lancet 339:267–269, 1992PubMedGoogle Scholar
  30. 30.
    Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A, Vogt HG, Herrmann F, Freund M, Meusers P, Salama A, Heimpel H: Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. N Engl J Med 324:1297–1304, 1991PubMedGoogle Scholar
  31. 31.
    Camitta BM, Thomas ED, Nathan DG, Gale RP, Kopecky KJ, Rappeport JM, Santos G, Gordon-Smith EC, Storb R: A prospective study of androgens and bone marrow transplantation for treatment of severe aplastic anemia. Blood 53:504–514, 1979PubMedGoogle Scholar
  32. 32.
    Hinterberger-Fischer M, Hinterberger W, Hoeckern P: Treatment of severe aplastic anemia with combined immunosuppression. Acta Haematol 76:196–201, 1986PubMedGoogle Scholar
  33. 33.
    Young N, Griffith P, Brittain E, Elfenbein G, Gardner F, Huang A, Harmon D, Hewlett J, Fay J, Mangan K, Morrison F, Sensenbrenner L, Shadduck R, Wang W, Zaroulis C, Zuckerman K: A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood 72:1861–1869, 1988PubMedGoogle Scholar
  34. 34.
    Gluckman E: Current status of bone marrow transplantation for severe aplastic anemia: A preliminary report from the International Bone Marrow Transplant Registry. Transplant Proc 19:2597–2599, 1987PubMedGoogle Scholar
  35. 35.
    Klingemann HG, Storb R, Fefer A: Bone marrow transplantation in patients aged 45 years and older. Blood 67:770–776, 1986PubMedGoogle Scholar
  36. 36.
    Hunter RF, Mold NG, Mitchell RB, Huang AT: Differentiation of normal marrow and HL60 cells induced by antithymocyte globulin. Proc Natl Acad Sci USA 82:4823–4827, 1985PubMedGoogle Scholar
  37. 37.
    Kawano Y, Nissen C, Gratwohl A, Speck B: Immunostimulatory effects of different antilymphocyte globulin preparations: A possible clue to their clinical effect. Br J Haematol 68:115–119, 1988PubMedGoogle Scholar
  38. 38.
    Stryckmans PA, Dumont JP, Velu T, Debusscher L: Cyclosporine in refractory severe aplastic anemia. N Engl J Med 310:655–656, 1984PubMedGoogle Scholar
  39. 39.
    Frickhofen N, Heit W, Raghavachar A, Porzolt F, Heimpel H: Treatment of aplastic anemia with cyclosporine A, methylprednisolone, and antithymocyte globulin. Klin Wochenschr 64:1165–1170, 1986PubMedGoogle Scholar
  40. 40.
    Pol S, Thiers V, Driss F, Devergie A, Berthelot P, Bréchot C, Gluckman E: Lack of evidence for a role of HCV in hepatitis-associated aplastic anemia. Br J Haematol 85:808–810, 1993PubMedGoogle Scholar
  41. 41.
    Hibbs JR, Frickhofen N, Rosenfeld SJ, Feinstone SM, Kojima S, Bacigalupo A, Locasciulli A, Tzakis AG, Alter HJ, Young NS: Aplastic anemia and viral hepatitis. Non-A, non-B, non-C? JAMA 267:2051–2054, 1992PubMedGoogle Scholar
  42. 42.
    McGuinness PH, Bishop GA, McCaughan GW, Trowbridge R, Gowans EJ: False detection of negative-strand of hepatitis C virus RNA. Lancet 343:551–552, 1994Google Scholar
  43. 43.
    Fong T-L, Shindo M, Feinstone SM, Hoofnagle JH, De Bisceglie AM: Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C. J Clin Invest 88:1058–1060, 1991PubMedGoogle Scholar
  44. 44.
    Müller HM, Kalliniowski B, Solbach C, Theilmann L, Goeser T, Pfaff E: B-lymphocytes are predominantly involved in viral propagation of hepatitis C virus (HCV). Arch Virol suppl 9:307–316, 1994PubMedGoogle Scholar
  45. 45.
    Lenzi M, Johnson PJ, McFarlane IG, Ballardini G, Smith HM, McFarlane BM, Bridger C, Vergani D, Bianchi FB, Williams R: Antibodies to hepatitis C virus in autoimmune liver disease; evidence for geographical heterogeneity. Lancet 338:1370–1378, 1991Google Scholar
  46. 46.
    Lunel F, Abuaf N, Frangeul L, Grippon P, Perrin M, Le Coz Y, Valla D, Yamamoto A-M, Huraux J-M, Opolon P, Homberg J-C: Liver/kidney microsome antibody type 1 and hepatitis C virus infection. Hepatology 16:630–636, 1992PubMedGoogle Scholar
  47. 47.
    Vergani D, Mieli-Vergani G: Type II autoimmune hepatitis: What is the role of hepatitis C virus? Gastroenterology 104:1870–1873, 1993PubMedGoogle Scholar
  48. 48.
    Manns MP, Griffin KJ, Sullivan KF, Johnson EF: LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 88:1370–1378, 1991PubMedGoogle Scholar
  49. 49.
    Homberg JC, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil SH, Poupon R, Darnis F, Levy V-G, Grippon P, Opolon P, Bernuau J, Benhamou J-P, Alagille D: Chronic active hepatitis associated with anti-liver/kidney microsome autoantibody type I: A second type of “autoimmune hepatitis.” Hepatology 7:1333–1339, 1987PubMedGoogle Scholar
  50. 50.
    Seki T, Kiyosawa K, Inoko H, Ota M: Association of autoimmune hepatitis with HLA BW 54 and DR 4 in Japanese patients. Hepatology 12:1300–1304, 1990PubMedGoogle Scholar
  51. 51.
    Manns M, Scheucher S, Jenisch, Broly F, Goergen B, Schneider P, Gerken G, Rittner C, Meyer zum Büschenfelde KH, Meyer U: Genetics in autoimmune hepatitis type 2. Hepatology 14:60A, 1991Google Scholar
  52. 52.
    Ferri C, Greco F, Longombardo G, Palla P, Moretti A, Marzo E, Fosella PV, Pasero G, Bondardieri S: Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia. Arthritis Rheum 34:1606–1610, 1991PubMedGoogle Scholar
  53. 53.
    Lunel F, Musset L, Cacoub P: Prevalence of mixed cryoglobulinemia in 112 patients with viral and non viral chronic hepatitis or cirrhosis. J Hepatol 16:13–20, 1992Google Scholar
  54. 54.
    Agnello V, Chung RT, Kaplan L: A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med 327:1490–1496, 1992PubMedGoogle Scholar
  55. 55.
    Cacoub P, Lunel Fabiani F, Musset L, Frangeul L, Leger JM, Huraux J-M, Piette J-C, Godeau P: Mixed cryoglobulinemia and hepatitis C virus. Am J Med 96:124–132, 1994PubMedGoogle Scholar
  56. 56.
    Misiani R, Bellavita P, Fenili D, Vicari O, Marchesi D, Sironi PL, Zilio P, Vernocchi A, Massazza M, Venramin G, Tanzi E, Zanetti A: Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 330:751–756, 1994PubMedGoogle Scholar
  57. 57.
    Bloch KJ: Cryoglobulinemia and hepatitis C virus. N Engl J Med 327:1521–1523, 1992PubMedGoogle Scholar
  58. 58.
    Gabrielli A, Manzin A, Candela M, Caniglia ML, Paolucci S, Danieli MG, Clementi M: Active hepatitis C virus infection in bone marrow and peripheral blood mononuclear cells from patients with mixed cryoglobulinemia. Clin Exp Immunol 97:87–93, 1994PubMedGoogle Scholar
  59. 59.
    Schlaak JF, Löhr H, Gallati H, Meyer zum Büschenfelde KH, Fleischer B: Analysis ofin vitro cytokine production by liver-infiltrating T cells of patients with autoimmune hepatitis. Clin Exp Immunol 94:168–173, 1993PubMedGoogle Scholar
  60. 60.
    Löhr HF, Schlaak JF, Gerken G, Fleischer B, Dienes HP, Meyer zum Büschenfelde KH: Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. Liver 14:161–166, 1994PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Malte Peters
    • 1
  • Martin Trippler
    • 1
  • Hanns Löhr
    • 1
  • Werner Gödderz
    • 1
  • Wolfgang Herr
    • 1
  • Stefan Störkel
    • 1
  • Karl-Hermann Meyer Zum Büschenfelde
    • 1
  • Guido Gerken
    • 1
  1. 1.I. Medizinische Klinik und PoliklinikJohannes Gutenberg-UniversitätMainzGermany

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