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Long-Term Course of Patients with Mixed Cryoglobulinemia

  • Damien Sene
  • Patrice P. Cacoub
Chapter

Abstract

The long-term course of mixed cryoglobulinemia during hepatitis C virus (HCV) infection is a function of chronic viral antigenic stimulation of B cells. The natural tendency of mixed cryoglobulins (MC) is the transition from type III to oligoclonal type and finally to type II MC, which mostly exhibit rheumatoid factor activity and are frequently associated with vasculitis. Disease evolution after treatment depends on its efficacy in inducing viral clearance. Combined PEGylated interferon-α and ribavirin is the most efficient treatment, resulting in a complete immunological response in most patients when associated with viral clearance. The use of rituximab, which specifically targets B cells and thus MC production, was shown to result in clinical and immunological responses in most patients, but with a high rate of relapse after treatment due to viral persistence. More recently, a combination of rituximab and antiviral agents was shown to provide the best approach to the treatment of HCV-related MC vasculitis, as it achieves both viral clearance and B-cell depletion.

Keywords

Sustained Virological Response Sustained Virological Response Rate Viral Clearance Mixed Cryoglobulinemia Sustained Viral Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Brouet JC, Clauvel JP, Danon F et al (1974) Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med 57(5):775–788PubMedCrossRefGoogle Scholar
  2. 2.
    Tridon A, Abergel A, Kuder P et al (1997) Mixed cryoglobulins and autoimmunity in hepatitis C. Pathol Biol (Paris) 45(4):291–297Google Scholar
  3. 3.
    Sène D, Ghillani-Dalbin P, Thibault V et al (2004) Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus. J Rheumatol 31(11):2199–2206PubMedGoogle Scholar
  4. 4.
    Meltzer M, Franklin EC, Elias K et al (1966) Cryoglo­bulinemia – a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med 40(6):837–856PubMedCrossRefGoogle Scholar
  5. 5.
    Cacoub P, Delluc A, Saadoun D et al (2008) Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemic vasculitis: where do we stand? Ann Rheum Dis 67(3):283–287PubMedCrossRefGoogle Scholar
  6. 6.
    Schifferli JA, French LE, Tissot JD (1995) Hepatitis C virus infection, cryoglobulinemia, and glomerulonephritis. Adv Nephrol Necker Hosp 24:107–129PubMedGoogle Scholar
  7. 7.
    Musset L, Diemert MC, Taibi F et al (1992) Characterization of cryoglobulins by immunoblotting. Clin Chem 38(6):798–802PubMedGoogle Scholar
  8. 8.
    De Vita S, De Re V, Gasparotto D et al (2000) Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia: clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma. Arthritis Rheum 43(1):94–102PubMedCrossRefGoogle Scholar
  9. 9.
    Sansonno D, De Vita S, Iacobelli AR et al (1998) Clonal analysis of intrahepatic B cells from HCV-infected patients with and without mixed cryoglobulinemia. J Immunol 160(7):3594–3601PubMedGoogle Scholar
  10. 10.
    Migliaresi S, Tirri G (1995) Interferon in the treatment of mixed cryoglobulinemia. Clin Exp Rheumatol 13(Suppl 13):S175–S180PubMedGoogle Scholar
  11. 11.
    Misiani R, Bellavita P, Fenili D et al (1994) Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 330(11):751–756PubMedCrossRefGoogle Scholar
  12. 12.
    Cohen P, Nguyen QT, Deny P et al (1996) Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients. Ann Med Interne (Paris) 147(2):81–86Google Scholar
  13. 13.
    Adinolfi LE, Utili R, Zampino R et al (1997) Effects of long-term course of alpha-interferon in patients with chronic hepatitis C associated to mixed cryoglobulinaemia. Eur J Gastroenterol Hepatol 9(11):1067–1072PubMedCrossRefGoogle Scholar
  14. 14.
    Polzien F, Schott P, Mihm S et al (1997) Interferon-alpha treatment of hepatitis C virus-associated mixed cryoglobulinemia. J Hepatol 27(1):63–71PubMedCrossRefGoogle Scholar
  15. 15.
    Casato M, Agnello V, Pucillo LP et al (1997) Predictors of long-term response to high-dose interferon therapy in type II cryoglobulinemia associated with hepatitis C virus infection. Blood 90(10):3865–3873PubMedGoogle Scholar
  16. 16.
    Calleja JL, Albillos A, Moreno-Otero R et al (1999) Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia. Aliment Pharmacol Ther 13(9):1179–1186PubMedCrossRefGoogle Scholar
  17. 17.
    Cresta P, Musset L, Cacoub P et al (1999) Response to interferon alpha treatment and disappearance of ­cryoglobulinaemia in patients infected by hepatitis C virus. Gut 45(1):122–128PubMedCrossRefGoogle Scholar
  18. 18.
    Naarendorp M, Kallemuchikkal U, Nuovo GJ et al (2001) Longterm efficacy of interferon-alpha for extrahepatic disease associated with hepatitis C virus infection. J Rheumatol 28(11):2466–2473PubMedGoogle Scholar
  19. 19.
    Cacoub P, Renou C, Kerr G et al (2001) Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum 44(9):2118–2124PubMedCrossRefGoogle Scholar
  20. 20.
    Cacoub P, Lidove O, Maisonobe T et al (2002) Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 46(12):3317–3326PubMedCrossRefGoogle Scholar
  21. 21.
    Cacoub P, Ratziu V, Myers RP et al (2002) Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C. J Hepatol 36(6):812–818PubMedCrossRefGoogle Scholar
  22. 22.
    Zuckerman E, Keren D, Slobodin G et al (2000) Treatment of refractory, symptomatic, hepatitis C virus related mixed cryoglobulinemia with ribavirin and interferon-alpha. J Rheumatol 27(9):2172–2178PubMedGoogle Scholar
  23. 23.
    Mazzaro C, Zorat F, Comar C et al (2003) Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon. J Rheumatol 30(8):1775–1781PubMedGoogle Scholar
  24. 24.
    Manns MP, McHutchison JG, Gordon SC et al (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358(9286):958–965PubMedCrossRefGoogle Scholar
  25. 25.
    Fried MW, Shiffman ML, Reddy KR et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347(13):975–982PubMedCrossRefGoogle Scholar
  26. 26.
    Saadoun D, Resche-Rigon M, Thibault V et al (2006) Antiviral therapy for hepatitis C virus–associated mixed cryoglobulinemia vasculitis: a long-term followup study. Arthritis Rheum 54(11):3696–3706PubMedCrossRefGoogle Scholar
  27. 27.
    Cacoub P, Saadoun D, Limal N et al (2005) PEGylated interferon alfa-2b and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis. Arthritis Rheum 52(3):911–915PubMedCrossRefGoogle Scholar
  28. 28.
    Zaja F, Russo D, Fuga G et al (1999) Rituximab for the treatment of type II mixed cryoglobulinemia. Haematologica 84(12):1157–1158PubMedGoogle Scholar
  29. 29.
    Zaja F, De Vita S, Russo D et al (2002) Rituximab for the treatment of type II mixed cryoglobulinemia. Arthritis Rheum 46(8):2252–2254, author reply 2254–2255PubMedCrossRefGoogle Scholar
  30. 30.
    Zaja F, De Vita S, Mazzaro C et al (2003) Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood 101(10):3827–3834PubMedCrossRefGoogle Scholar
  31. 31.
    Sansonno D, De Re V, Lauletta G et al (2003) Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood 101(10):3818–3826PubMedCrossRefGoogle Scholar
  32. 32.
    Roccatello D, Baldovino S, Rossi D et al (2004) Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis. Nephrol Dial Transplant 19(12):3054–3061PubMedCrossRefGoogle Scholar
  33. 33.
    Lamprecht P, Lerin-Lozano C, Merz H et al (2003) Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis. Ann Rheum Dis 62(12):1230–1233PubMedCrossRefGoogle Scholar
  34. 34.
    Catuogno M, Rezai S, Priori R et al (2005) Serum sickness associated with rituximab in a patient with hepatitis C virus-related mixed cryoglobulinaemia. Rheumatology (Oxford) 44(3):406CrossRefGoogle Scholar
  35. 35.
    Basse G, Ribes D, Kamar N et al (2005) Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients. Transplantation 80(11):1560–1564PubMedCrossRefGoogle Scholar
  36. 36.
    Saadoun D, Resche-Rigon M, Sene D et al (2008) Rituximab combined with peg-interferon-ribavirin in refractory HCV-associated cryoglobulinemia vasculitis. Ann Rheum Dis 67(10):1431–1436PubMedCrossRefGoogle Scholar
  37. 37.
    Saadoun D, Resche Rigon M, Sene D et al (2010) Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia. Blood 116(3):326–334PubMedCrossRefGoogle Scholar
  38. 38.
    Dammacco F, Tucci FA, Lauletta G et al (2010) Pegylated interferon-alpha, ribavirin, and rituximab combined therapy of hepatitis C virus-related mixed cryoglobulinemia: a long-term study. Blood 116(3):343–353PubMedCrossRefGoogle Scholar
  39. 39.
    Sène D, Ghillani-Dalbin P, Amoura Z et al (2009) Rituximab may form a complex with IgMkappa mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus-induced vasculitis. Arthritis Rheum 60(12): 3848–3855PubMedCrossRefGoogle Scholar
  40. 40.
    Visentini M, Granata M, Veneziano ML et al (2007) Efficacy of low-dose rituximab for mixed cryoglobulinemia. Clin Immunol 125(1):30–33PubMedCrossRefGoogle Scholar
  41. 41.
    Levine JW, Gota C, Fessler BJ et al (2005) Persistent cryoglobulinemic vasculitis following successful treatment of hepatitis C virus. J Rheumatol 32(6):1164–1167PubMedGoogle Scholar
  42. 42.
    Landau DA, Saadoun D, Halfon P et al (2008) Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response. Arthritis Rheum 58(2):604–611PubMedCrossRefGoogle Scholar
  43. 43.
    Terrier B, Saadoun D, Sene D et al (2009) Efficacy and tolerability of rituximab with or without PEGylated interferon alfa-2b plus ribavirin in severe hepatitis C virus-related vasculitis: a long-term followup study of thirty-two patients. Arthritis Rheum 60(8):2531–2540PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  1. 1.Department of Internal MedicineHôpital La Pitié-SalpêtrièreParisFrance
  2. 2.Department of Internal MedicineHôpital La Pitié SalpêtrièreParisFrance
  3. 3.UMR 7211 (UPMC/CNRS), U 959 (INSERM)Université Pierre Marie CurieParisFrance

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