Advertisement

Antiviral Therapy in HCV-Positive Non-Hodgkin’s Lymphoma: Pathogenetic Implications

  • Franco Dammacco
  • Cinzia Conteduca
  • Domenico Sansonno
Chapter

Abstract

Growing evidence indicates an association between chronic HCV infection, with or without mixed cryoglobulinemia, and a subset of B-cell non-Hodgkin’s lymphoma (B-NHL), although geographical heterogeneity has been described in its prevalence. In addition to persistent antigenic stimulation by HCV that results in the maintenance of clonal B-cell proliferation, genetic and environmental factors have been suggested to play a role in the progression to frank lymphoid malignancy. In a retrospective cohort study carried out in the USA, HCV infection was determined to confer a 20–30% increased risk of developing B-NHL as compared with uninfected patients. In Italy, approximately 5% of all B-NHLs are believed to be causally related to HCV. On the basis of these considerations, an effective antiviral therapy and the ensuing sustained virological response (SVR) would be expected to induce the regression of B-NHL. This was first shown in 2002 in patients with splenic lymphoma with villous lymphocytes. A systematic review of subsequent studies reported that 75% of HCV-infected patients with B-NHL treated with pegylated interferon-α (pIFN-α) plus ribavirin (RBV) achieved a complete hematological response (CHR), whereas no such response was obtained in matched HCV-uninfected B-NHL patients. Our own experience refers to a retrospective analysis: 10 out of 13 (77%) HCV-positive patients with B-NHL achieved a SVR and 8 of them (61%) were considered to be in CHR following 1 year of combined pIFN-α plus RBV therapy. By contrast, CHR was observed in a lower percentage (33%) and for a shorter duration among 15 additional HCV-positive patients with B-NHL who received the same antiviral therapy but had been treated with one or more chemotherapeutic regimens. Further studies are required to gain a deeper insight of the relationships between HCV infection and lymphomagenesis.

Keywords

Sustained Virological Response Antiviral Therapy Bone Marrow Biopsy Complete Hematological Response Cryoglobulinemic Vasculitis 
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.
    Schultz DR, Yunis AA (1975) Immunoblastic lymphadenopathy with mixed cryoglobulinemia. A detailed case study. N Engl J Med 292:8–12PubMedCrossRefGoogle Scholar
  2. 2.
    Monteverde A, Rivano MT, Allegra GC et al (1988) Essential mixed cryoglobulinemia, type II: a manifestation of a low-grade malignant lymphoma? Clinical-morphological study of 12 cases with special reference to immunohistochemical findings in liver frozen sections. Acta Haematol 79:20–25PubMedCrossRefGoogle Scholar
  3. 3.
    Monteverde A, Sabattini E, Poggi S et al (1995) Bone marrow findings further support the hypothesis that essential mixed cryoglobulinemia type II is characterized by a monoclonal B-cell proliferation. Leuk Lymphoma 20:119–124PubMedCrossRefGoogle Scholar
  4. 4.
    Ferri C, Caracciolo F, Zignego AL et al (1994) Hepatitis C virus infection in patients with non-Hodgkin’s lymphoma. Br J Haematol 88:392–394PubMedCrossRefGoogle Scholar
  5. 5.
    Mazzaro C, Zagonel V, Monfardini S et al (1996) Hepatitis C virus and non-Hodgkin’s lymphomas. Br J Haematol 94:544–550PubMedCrossRefGoogle Scholar
  6. 6.
    Silvestri F, Pipan C, Barillari G et al (1996) Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders. Blood 87:4296–4301PubMedGoogle Scholar
  7. 7.
    Pozzato G, Mazzaro C, Crovatto M et al (1994) Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia. Blood 84:3047–3053PubMedGoogle Scholar
  8. 8.
    Luppi M, Ferrari MG, Bonaccorsi G et al (1996) Hepatitis C virus infection in subsets of neoplastic lymphoproliferations not associated with cryoglobulinemia. Leukemia 10:351–355PubMedGoogle Scholar
  9. 9.
    Rasul I, Shepherd FA, Kamel-Reid S et al (1999) Detection of occult low-grade b-cell non-Hodgkin’s lymphoma in patients with chronic hepatitis C infection and mixed cryoglobulinemia. Hepatology 29:543–547PubMedCrossRefGoogle Scholar
  10. 10.
    Marcucci F, Mele A (2011) Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood 117:1792–1798PubMedCrossRefGoogle Scholar
  11. 11.
    Dammacco F, Sansonno D, Piccoli C et al (2000) The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and overt B-cell malignancy. Semin Liver Dis 20:143–157PubMedCrossRefGoogle Scholar
  12. 12.
    Zignego AL, Giannini C, Ferri C (2007) Hepatitis C virus-related lymphoproliferative disorders: an overview. World J Gastroenterol 13:2467–2478PubMedGoogle Scholar
  13. 13.
    Giordano TP, Henderson L, Landgren O et al (2007) Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA 297:2010–2017PubMedCrossRefGoogle Scholar
  14. 14.
    Saadoun D, Landau DA, Calabrese LH et al (2007) Hepatitis C-associated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation. Rheumatology (Oxford) 46:1234–1242CrossRefGoogle Scholar
  15. 15.
    Libra M, Polesel J, Russo AE et al (2010) Extrahepatic disorders of HCV infection: a distinct entity of B-cell neoplasia? Int J Oncol 36:1331–1340PubMedCrossRefGoogle Scholar
  16. 16.
    Gisbert JP, Garcia-Buey L, Pajares JM et al (2003) Prevalence of hepatitis C virus infection in B-cell non-Hodgkin’s lymphoma: systematic review and meta-analysis. Gastroenterology 125:1723–1732PubMedCrossRefGoogle Scholar
  17. 17.
    Negri E, Little D, Boiocchi M et al (2004) B-cell non-Hodgkin’s lymphoma and hepatitis C virus infection: a systematic review. Int J Cancer 111:1–8PubMedCrossRefGoogle Scholar
  18. 18.
    Fiorilli M, Mecucci C, Farci P et al (2003) HCV-associated lymphomas. Rev Clin Exp Hematol 7:406–423PubMedGoogle Scholar
  19. 19.
    McColl MD, Singer IO, Tait RC et al (1997) The role of hepatitis C virus in the aetiology of non-Hodgkins lymphoma–a regional association? Leuk Lymphoma 26:127–130PubMedGoogle Scholar
  20. 20.
    Kawamura Y, Ikeda K, Arase Y et al (2007) Viral elimination reduces incidence of malignant lymphoma in patients with hepatitis C. Am J Med 120:1034–1041PubMedCrossRefGoogle Scholar
  21. 21.
    Weng WK, Levy S (2003) Hepatitis C virus (HCV) and lymphomagenesis. Leuk Lymphoma 44:1113–1120PubMedCrossRefGoogle Scholar
  22. 22.
    Hermine O, Lefrère F, Bronowicki JP et al (2002) Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 347:89–94PubMedCrossRefGoogle Scholar
  23. 23.
    Gisbert JP, García-Buey L, Pajares JM et al (2005) Systematic review: regression of lymphoproliferative disorders after treatment for hepatitis C infection. Aliment Pharmacol Ther 21:653–662PubMedCrossRefGoogle Scholar
  24. 24.
    Vallisa D, Bernuzzi P, Arcaini L et al (2005) Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin’s lymphoma: a multicenter Italian experience. J Clin Oncol 23:468–473PubMedCrossRefGoogle Scholar
  25. 25.
    Harris NL, Jaffe ES, Diebold J et al (2000) Lymphoma classification–from controversy to consensus: the R.E.A.L. and WHO Classification of lymphoid neoplasms. Ann Oncol 11(Suppl 1):3–10PubMedCrossRefGoogle Scholar
  26. 26.
    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 116:343–353PubMedCrossRefGoogle Scholar
  27. 27.
    Stathis A, Bertoni F, Zucca E (2010) Treatment of gastric marginal zone lymphoma of MALT type. Expert Opin Pharmacother 11:2141–2152PubMedCrossRefGoogle Scholar
  28. 28.
    Lin WC, Tsai HF, Kuo SH et al (2010) Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res 70:5740–5748PubMedCrossRefGoogle Scholar
  29. 29.
    Kasama Y, Sekiguchi S, Saito M et al (2010) Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo. Blood 116:4926–4933PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Franco Dammacco
    • 1
  • Cinzia Conteduca
    • 1
  • Domenico Sansonno
    • 2
  1. 1.Department of Internal Medicine and Clinical OncologyUniversity of Bari Medical SchoolBariItaly
  2. 2.Liver Unit, Department of Biomedical Sciences and Clinical OncologyUniversity of Bari Medical SchoolBariItaly

Personalised recommendations