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B cell non-Hodgkin’s lymphoma in chronic hepatitis C virus patients: An interesting relationship

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Abstract

Background

An association exists between hepatitis C virus (HCV) infection and non-Hodgkin’s lymphoma (NHL), but a causal relationship is not fully established. HCV is a lymphotropic virus that represents a major etiologic agent of mixed cryoglobulinemia (MC) type II which is characterized by a low-grade B cell clonal lymphoproliferative disorder that usually progresses to a more aggressive malignant lymphoma. This study assessed the role of cryoglobulin and B lymphocyte stimulator (BLys) in the pathogenesis of NHL in chronic HCV patients.

Methods

Sixty HCV patients, 30 free of B cell NHL (group I) and 30 with B cell NHL (group II), and 30 healthy controls (group III) were studied. Qualitative cryoglobulin assessment and a quantitative assay for BLys were done.

Results

In group II, BLyS positivity rate was 1.5-fold higher than of group I (p ≤ 0.01). A positive association was found between positivity rate of MC and the level of BLyS (p ≤ 0.01).

Conclusion

High BLyS levels were associated with HCV-associated lymphoproliferative disorder coupled with positive MC.

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References

  1. Dal Maso L, Franceschi S. Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies. Cancer Epidemiol Biomarkers Prev. 2006;15:2078–85.

    Article  CAS  PubMed  Google Scholar 

  2. Matsuo K, Kusano A, Sugumar A, Nakamura S, Tajima K, Mueller NE. Effect of hepatitis C virus infection on the risk of non-Hodgkin’s lymphoma: a meta-analysis of epidemiological studies. Cancer Sci. 2004;95:745–52.

  3. Anderson LA, Engels EA. Hepatitis C virus infection and non-Hodgkin lymphoma: interesting association or causal relationship? Int J Cancer. 2008;122:10–12.

  4. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med. 1995;123:615–20.

  5. Pozzato G, Mazzaro C, Crovatto M, et al. Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia. Blood. 1994;84:3047–53.

  6. Freedman SO. Clinical Immunology. Harper and Row: New York; 1971. p. 336–7.

  7. Usha K, Peter D. Evaluation of cryoglobulins. Arch Pathol Lab Med. 1999;123:119–21.

    Google Scholar 

  8. Sung WK, Lee WH. Fast and accurate probe selection algorithm for large genomes. Proc IEEE Comput Soc Bioinform Conf. 2003;2:65–74.

    PubMed  Google Scholar 

  9. Landau DA, Rosenzwajg M, Saadoun D, Klatzmann D, Cacoub P. The B lymphocyte stimulator receptor-ligand system in hepatitis C virus induced B cell clonal disorders. Ann Rheum Dis. 2011;68:337–44.

  10. Avery DT, Kalled SL, Ellyard JI, et al. BAFF selectively enhances the survival of plasmablasts generated from human memory cells. J Clin Invest. 2003;112:286–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Mackay F, Schneider P, Rennert P, Browning J. BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2002;21:231–64.

  12. Vincent FB, Northcott M, Hoi A, Mackay F, Morand EF. Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with central nervous system and renal disease in systemic lupus erythematosus. Lupus. 2013;22:873--84.

  13. Bosello S, Pers JO, Rochas C, et al. BAFF and rheumatic autoimmune disorders: implications for disease management and therapy. Int J Immunopathol Pharmacol. 2007;20:1–8.

    CAS  PubMed  Google Scholar 

  14. Moreaux J, Legouffe E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103:3148–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Toubi E, Gordon S, Kessel A, et al. Elevated serum B-lymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: association with autoimmunity. J Autoimmun. 2006;27:134–9.

    Article  CAS  PubMed  Google Scholar 

  16. Fabris M, Quartuccio L, Sacco S, et al. B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection. Rheumatology. 2007;46:37–43.

    Article  CAS  PubMed  Google Scholar 

  17. Craxton A, Magaletti D, Ryan EJ, Clark EA. Macrophage- and dendritic cell-dependent regulation of human B-cell proliferation require the TNF family ligand BAFF. Blood. 2002;101:4464–71.

  18. Metz CE. Basic principles of ROC analysis. Semin Nucl Med. 1978;8:283–98.

    Article  CAS  PubMed  Google Scholar 

  19. Luppi M, Ferrari MG, Bonaccorsi G, et al. Hepatitis C virus infection in subsets of neoplastic lympho-proliferations not associated with cryoglobulinemia. Leukemia. 1996;10:351–5.

    CAS  PubMed  Google Scholar 

  20. Ferri C, Greco F, Longombardo G, et al. Association between hepatitis C virus and mixed cryoglobulinemia. Clin Exp Rheumatol. 1991;9:621–4.

    CAS  PubMed  Google Scholar 

  21. Lunel F, Musset L, Cacoub P, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology. 1994;106:1291–300.

    CAS  PubMed  Google Scholar 

  22. Kayali Z, Buckwold VE, Zimmerman B, Schmidt WN. Hepatitis C, cryoglobulinemia, and cirrhosis: a meta-analysis. Hepatology. 2002;36:978–85.

  23. Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, et al. Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol. 2007;13:6518--28.

  24. Kamal SM, Nasser IA. Hepatitis C genotype 4: what we know and what we don’t yet know. Hepatology. 2008;47:1371--83.

  25. Sansonno D, Carbone A, De Re V, Dammacco F. Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford). 2007;46:572–8.

  26. Abbas OM, Omar NA, Hassan ZK. T (14;18) is not associated with mixed cryoglobulinemia or with clonal B cell expansion in Egyptian patients with hepatitis C virus infection. J Egypt Natl Canc Inst. 2008;20:149–57.

    PubMed  Google Scholar 

  27. Jadali Z. Hepatitis C, virus cryoglobulinemia and non-Hodgkin lymphoma. Hepat Mon. 2012;12:85–91.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Ferri C, Longombardo G, La Civita L, et al. Hepatitis C virus chronic infection as a common cause of mixed cryoglobulinaemia and autoimmune liver disease. J Intern Med. 1994;236:31–6.

    Article  CAS  PubMed  Google Scholar 

  29. Ferri C, Zignego AL, Bombardieri S, et al. Etiopathogenetic role of hepatitis C virus in mixed cryoglobulinemia, chronic liver diseases and lymphomas. Clin Exp Rheumatol. 1995;13 Suppl 13:S135–40.

    PubMed  Google Scholar 

  30. Zignego AL, Ferri C, Giannelli F, et al. Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas. Ann Intern Med. 2002;137:571–80.

    Article  CAS  PubMed  Google Scholar 

  31. Zignego AL, Gragnani L, Giannini C, Laffi G. The hepatitis C virus infection as a systemic disease. Intern Emerg Med. 2012;7 Suppl 3:S201–8.

  32. Pozzato G, Burrone O, Baba K, et al. Ethnic difference in the prevalence of monoclonal B-cell proliferation in patients affected by hepatitis C virus chronic liver disease. J Hepatol. 1999;30:990–4.

  33. Fognani E, Giannini C, Piluso A, et al. Role of microRNA profile modifications in hepatitis C virus-related mixed cryoglobulinemia. PLoS One. 2013;8:e62965.

  34. Gragnani L, Piluso A, Giannini C, et al. Genetic determinants in hepatitis C virus-associated mixed cryoglobulinemia: role of polymorphic variants of BAFF promoter and Fcγ receptors. Arthritis Rheum. 2011;63:1446–51.

    Article  CAS  PubMed  Google Scholar 

  35. Gragnani L, Fognani E, Piluso A, Zignego AL. Hepatitis C-associated B-cell non-Hodgkin lymphomas: the emerging role of miRNA-26b. J Hepatol. 2013;59:1362–3.

  36. Sène D, Limal N, Ghillani-Dalbin P, Saadoun D, Piette JC, Cacoub P. Hepatitis C virus-associated B-cell proliferation-the role of serum B lymphocyte stimulator (BLyS/BAFF). Rheumatology. 2007;46:65–9.

  37. Moorman J, Dong ZP, Ni L, Zhang C, Borthwick T, Yao ZQ. Abnormal B-cell activation associated with TALL-1 over-expression and SOCS-1 suppression during chronic hepatitis C virus infection. Immunology. 2009;128:227–35.

  38. de Sanjose S, Benavente Y, Vajdic CM, et al. Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium. Clin Gastroenterol Hepatol. 2008;6:451–8.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Ferri C, Sebastiani M, Giuggioli D, et al. Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients. Semin Arthritis Rheum. 2004;33:355–74.

    Article  PubMed  Google Scholar 

  40. Montella M, Crispo A, de Bellis G, et al. HCV and cancer: a case–control study in a high endemic area. Liver. 2001;21:335–41.

    Article  CAS  PubMed  Google Scholar 

  41. Hausfater P, Cacoub P, Sterkers Y, et al. Hepatitis C virus infection and lympho-proliferative diseases: prospective study on 1,576 patients in France. Am J Hematol. 2001;67:168–71.

    Article  CAS  PubMed  Google Scholar 

  42. Besson C, Canioni D, Lepage E, et al. 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. 2006;24:953–60.

    Article  PubMed  Google Scholar 

  43. Ennishi D, Maeda Y, Niitsu N, et al. Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis. Blood. 2010;116:5119–25.

    Article  CAS  PubMed  Google Scholar 

  44. Grudeva-Popova J, Nenova I, Mateva N, Ananoshtev N, Popov V, Atanasova M. Non-Hodgkin lymphomas and carrier state of viral hepatitis B and C. J BUON. 2013;18:239–44.

    CAS  PubMed  Google Scholar 

  45. Farawela H, Khorshied M, Shaheen I, et al. The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin’s lymphoma risk in Egypt. Infect Genet Evol. 2012;12:1189–94.

    Article  CAS  PubMed  Google Scholar 

  46. Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S. Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management. J Hepatol. 2013;59:169–77.

  47. Monti G, Pioltelli P, Saccardo F, et al. Incidence and characteristics of non-Hodgkin lymphomas in a multicenter case file of patients with hepatitis C virus-related symptomatic mixed cryoglobulinemias. Arch Intern Med. 2005;165:101–5.

    Article  PubMed  Google Scholar 

  48. Cacoub P, Poynard T, Ghillani P, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC group Multidepartment Virus C. Arthritis Rheum. 1999;42:2204–12.

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Conflict of interest

HSH, NAA, AM, EHA, HME-W, and DE have declared that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The study was performed in a manner to conform with the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning Human and Animal Rights, and the authors followed the policy concerning Informed Consent as shown on Springer.com.

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Correspondence to Nadia A. Abdelkader.

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Hamdy, H.S., Abdelkader, N.A., Mansour, A. et al. B cell non-Hodgkin’s lymphoma in chronic hepatitis C virus patients: An interesting relationship. Indian J Gastroenterol 34, 127–134 (2015). https://doi.org/10.1007/s12664-015-0549-4

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