The Higher Prevalence of B-Cell Non-Hodgkin’s Lymphoma in HCV-Positive Patients with and Without Cryoglobulinemia



Hepatitis C virus (HCV) is a major cause of liver-related morbidity and is increasingly linked to a subgroup of B cell lymphoproliferative disorders. On the strength of epidemiological data, emerging biological investigation, and clinical observations, HCV appears to be involved in the pathogenesis of B-cell non-Hodgkin’s lymphoma (NHL) in a subset of patients. Morphologically, HCV-associated NHLs encompass a variety of histological subtypes, including marginal zone, small lymphocytic lymphoma/chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and diffuse large B-cell lymphoma. Remarkably, some HCV-associated NHLs are highly responsive to antiviral therapy.


Mixed Cryoglobulinemia Chronic Antigenic Stimulation Human Herpes Virus Type Lymphoplasmacytic Lymphoma Tropical Spastic Paraparesis 
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.


  1. 1.
    Butel JS (2000) Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcino­genesis 21:405–426PubMedCrossRefGoogle Scholar
  2. 2.
    Tsai WL, Chung RT (2010) Viral hepatocarcinogenesis. Oncogene 29:2309–2324PubMedCrossRefGoogle Scholar
  3. 3.
    Raab-Traub N (1999) Epstein-Barr virus, lymphoproliferative disease and nasopharingeal carcinoma. In: Parsonnet J (ed) Microbes and malignancy. Infection as cause of human cancers. Oxford University Press, Oxford, pp 180–206Google Scholar
  4. 4.
    Martin D, Gutkind JS (2008) Human tumor-associated viruses and new insights into the molecular mechanisms of cancer. Oncogene 27(Suppl 2):S31–S42PubMedCrossRefGoogle Scholar
  5. 5.
    Boxus M, Willems L (2009) Mechanisms of HTLV-1 persistence and transformation. Br J Cancer 101:1497–1501PubMedCrossRefGoogle Scholar
  6. 6.
    Ganem D (2010) KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Invest 120:939–949PubMedCrossRefGoogle Scholar
  7. 7.
    Carbone M, Rizzo P, Pass HI (1997) Simian virus 40, poliovaccines and human tumors: a review of recent developments. Oncogene 15:1877–1888PubMedCrossRefGoogle Scholar
  8. 8.
    Relman DA (1999) Chronic host-parasite interactions. In: Parsonnet J (ed) Microbes and malignancy. Infection as cause of human cancers. Oxford University Press, Oxford, pp 19–34Google Scholar
  9. 9.
    Sansonno D, Lauletta G, Montrone M et al (2006) Virological analysis and phenotypic characterization of peripheral blood lymphocytes of hepatitis C virus-infected patients with and without mixed cryoglobulinaemia. Clin Exp Immunol 143:288–296PubMedCrossRefGoogle Scholar
  10. 10.
    Stamataki Z, Shannon-Lowe C, Shaw J et al (2009) Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells. Blood 113:585–593PubMedCrossRefGoogle Scholar
  11. 11.
    Fung J, Lai CL, Yuen MF (2009) Hepatitis B and C virus-related carcinogenesis. Clin Microbiol Infect 15:964–970PubMedCrossRefGoogle Scholar
  12. 12.
    Esteban JI, Sauleda S, Quer J (2008) The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 48:148–162PubMedCrossRefGoogle Scholar
  13. 13.
    Dammacco F, Gatti P, Sansonno D (1998) Hepatitis C virus infection, mixed cryoglobulinemia, and non-Hodgkin’s lymphoma: an emerging picture. Leuk Lymphoma 31:463–476PubMedGoogle Scholar
  14. 14.
    Vajdic CM, Grulich AE, Kaldor JM et al (2006) Specific infections, infection-related behavior, and risk of non-Hodgkin lymphoma in adults. Cancer Epidemiol Biomarkers Prev 15:1102–1108PubMedCrossRefGoogle Scholar
  15. 15.
    Cowgill KD, Loffredo CA, Elissa SA et al (2004) Case-control study of non-Hodgin’s lymphoma and hepatitis C virus infection in Egypt. Int J Epidemiol 33:1034–1039PubMedCrossRefGoogle Scholar
  16. 16.
    Seve P, Renaudier P, Sasco AJ et al (2004) Hepatitis C virus infection and B-cell non-Hodgin’s lymphoma: a cross-sectional study in Lyon, France. Eur J Gastroenterol Hepatol 16:1361–1365PubMedCrossRefGoogle Scholar
  17. 17.
    Vallisa D, Berte R, Rocca A et al (1999) Association between hepatitis C virus and non-Hodgkin’s lymphoma, and effects of viral infection on histologic subtype and clinical course. Am J Med 106:556–560PubMedCrossRefGoogle Scholar
  18. 18.
    Pioltelli P, Gargantini L, Cassi E et al (2000) Hepatitis C virus in non-Hodgkin’s lymphoma. A reappraisal after a prospective case-control study of 300 patients. Lombart Study Group of HCV-Lymphoma. Am J Hematol 64:95–100PubMedCrossRefGoogle Scholar
  19. 19.
    Montella M, Crispo A, Frigeri F et al (2001) HCV and tumors correlated with immune system: a case-control study in an area of hyperendemicity. Leuk Res 25:775–781PubMedCrossRefGoogle Scholar
  20. 20.
    Mele A, Pulsoni A, Bianco E et al (2003) Hepatitis C virus and -cell non-Hodgkin lymphomas: an Italian multicenter case control study. Blood 102:996–999PubMedCrossRefGoogle Scholar
  21. 21.
    Talamini R, Montella M, Crovatto M et al (2004) Non-Hodgkin’s lymphoma and hepatitis C virus: a case-control study from northern and southern Italy. Int J Cancer 110:380–385PubMedCrossRefGoogle Scholar
  22. 22.
    Mizorogi F, Hiramoto J, Nozato A et al (2000) Hepatitis C virus infection in patients with B-cell non-Hodgkin’s lymphoma. Intern Med 39:112–117PubMedCrossRefGoogle Scholar
  23. 23.
    Imai Y, Ohsawa M, Tanaka H et al (2002) High prevalence of HCV infection in patients with B-cell non-Hodgkin’s lymphoma: comparison with birth cohort- and sex-matched blood donors in a Japanese population. Hepatology 35:974–976PubMedCrossRefGoogle Scholar
  24. 24.
    Kim JH, Bang YJ, Park BJ et al (2002) Hepatitis B virus infection and B cell non-Hodgkin’s lymphoma in heatitis B endemic area: a case-control study. Jpn J Cancer 93:471–477CrossRefGoogle Scholar
  25. 25.
    de Sanjose S, Nieters A, Goedert JJ et al (2004) Role of hepatitis C virus infection in malignant lymphoma in Spain. Int J Cancer 111:81–85PubMedCrossRefGoogle Scholar
  26. 26.
    Zuckerman E, Zuckerman T, Levine AM et al (1997) Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma. Ann Intern Med 127:423–428PubMedCrossRefGoogle Scholar
  27. 27.
    Engels EA (2007) Infectious agents as causes of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 16:401–404PubMedCrossRefGoogle Scholar
  28. 28.
    Morton LM, Engels EA, Holford TR et al (2004) Hepatitis C virus and risk of non-Hodgkin lymphoma: a population-based case-control study among Connecticut women. Cancer Epidemiol Biomarkers Prev 13:425–430PubMedGoogle Scholar
  29. 29.
    Engels EA, Chatterjee N, Cerhan JR et al (2004) Hepatitis C virus infection and non-Hodgkin lymphoma: results of the NCI-SEER multi-center case-control study. Int J Cancer 111:76–80PubMedCrossRefGoogle Scholar
  30. 30.
    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
  31. 31.
    Nieters A, Kallinowski B, Brennan P et al (2006) Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology 131:1879–1886PubMedCrossRefGoogle Scholar
  32. 32.
    de Sanjose S, Benavente Y, Vajdic CM et al (2008) Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. Clin Gastroenterol Hepatol 6:451–458PubMedCrossRefGoogle Scholar
  33. 33.
    Besson C, Canioni D, Lepage E et al (2006) Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol 24:953–960PubMedCrossRefGoogle Scholar
  34. 34.
    Waters L, Stebbing J, Mandalia S et al (2005) Hepatitis C infection is not associated with systemic HIV-associated non-Hodgkin’s lymphoma: a cohort study. Int J Cancer 116:161–163PubMedCrossRefGoogle Scholar
  35. 35.
    Franceschi S, Polesel J, Rickenbach M et al (2006) Hepatitis C virus and non-Hodgkin’s lymphoma: findings from the Swiss HIV Cohort Study. Br J Cancer 95:1598–1602PubMedCrossRefGoogle Scholar
  36. 36.
    Sansonno D, Dammacco F (2005) Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis 5:227–236PubMedCrossRefGoogle Scholar
  37. 37.
    Ryan J, Wallace S, Jones P et al (1994) Primary hepatic lymphoma in a patient with chronic hepatitis C. J Gastroenterol Hepatol 9:308–310PubMedCrossRefGoogle Scholar
  38. 38.
    De Vita S, Sacco C, Sansonno D et al (1997) Characterization of overt B-cell lymphomas in patients with hepatitis C virus infection. Blood 90:776–782PubMedGoogle Scholar
  39. 39.
    Pal S, Sullivan DG, Kim S et al (2006) Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism. Gastroenterology 130:1107–1116PubMedCrossRefGoogle Scholar
  40. 40.
    Lescar J, Canard B (2009) RNA-dependent RNA polymerases from flaviviruses and Picornaviridae. Curr Opin Struct Biol 19:759–767PubMedCrossRefGoogle Scholar
  41. 41.
    Sansonno D, Tucci FA, Lauletta G et al (2007) Hepatitis C virus productive infection in mononuclear cells from patients with cryoglobulinaemia. Clin Exp Immunol 147:241–248PubMedCrossRefGoogle Scholar
  42. 42.
    Budkowska A (2009) Mechanism of cell infection with hepatitis C virus (HCV)–a new paradigm in virus-cell interaction. Pol J Microbiol 58:93–98PubMedGoogle Scholar
  43. 43.
    Sansonno D, Lotesoriere C, Cornacchiulo V et al (1998) Hepatitis C virus infection involves CD34(+) hematopoietic progenitor cells in hepatitis C virus chronic carriers. Blood 92:3328–3337PubMedGoogle Scholar
  44. 44.
    Sansonno D, De Vita S, Cornacchiulo V et al (1996) Detection and distribution of hepatitis C virus-related ­proteins in lymph nodes of patients with type II mixed ­cryoglobulinemia and neoplastic or non-neoplastic lymphoproliferation. Blood 88:4638–4645PubMedGoogle Scholar
  45. 45.
    Irshad M, Dhar I (2006) Hepatitis C virus core protein: an update on its molecular biology, cellular functions and clinical implications. Med Princ Pract 15:405–4016PubMedCrossRefGoogle Scholar
  46. 46.
    Koike K, Tsutsumi T, Fujie H et al (2002) Molecular mechanism of viral hepatocarcinogenesis. Oncology 62(Suppl 1):29–37PubMedCrossRefGoogle Scholar
  47. 47.
    Hermine O, Lefrere 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
  48. 48.
    Psyrri A, Papageorgiou S, Economopoulos T (2008) Primary extranodal lymphomas of stomach: clinical presentation, diagnostic pitfalls and management. Ann Oncol 19(12):1992–1999PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  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