Acta Medica Iranica 2018. 56(7):441-449.

Hepatitis C-Associated Chronic Lymphoproliferative Disorders: A Single Center Experience
Doaa M El Demerdash, Heba Moustafa, Rasha S El Rawi, Sherif N Amin, Mervat M Mattar


Hepatitis C virus (HCV) infection is a major public health concern in Egypt with its unique genotype. Besides liver disease, HCV is a lymphotropic virus involved in the pathogenesis of various extrahepatic diseases. A causative role of HCV in the generation of chronic lymphoproliferative diseases as well as its impact on disease behavior in HCV chronic carriers are not fully understood. We investigated the prevalence of HCV among cohort of Egyptian patients (n:84) with chronic lymphoproliferative diseases, the relation between HCV infection and the immunological state of this population and also their clinical and laboratory characteristics. High prevalence of HCV (40%) among Egyptian patients with chronic lymphoproliferative diseases with following subtype frequency was revealed; CLL (38.2%) followed by DLBCL (20.6%), and LPL (17.6%). We found significant correlation between HCV and platelet count (P=0.014), Albumin (P=0.02), LDH (P=0.014) and B2M (P=0.05). Otherwise, there were no significant correlations with other parameters especially the immunological assessment; serum immunoglobulins, Coombs test, and cryoglobulinemia. HCV prevalence among patients with chronic lymphoproliferative diseases is higher than that estimated in the general population. Those patients should be tested for HCV during the assessment. Our observations suggest that HCV may have an oncogenic role in Egyptian patients with chronic lymphoproliferative diseases and it may affect the prognostic markers in those populations.


Hepatitis C virus; Non-hodgkin’s lymphoma; Chronic lymphoproliferative disorders; Cryoglobulinemia

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Kuiken C, Simmonds P. Nomenclature and numbering of the hepatitis C virus. Methods Mol Biol 2009;510:33-53.

Waked I, Doss W, El-Sayed MH, Estes C, Razavi H, Shiha G, et al. The current and future disease burden of chronic hepatitis C virus infection in Egypt. Arab J Gastroenterol 2014;15:45-52.

Pozzato G, Mazzaro C, Dal Maso L, Mauro E, Zorat F, Moratelli G, et al. Hepatitis C virus and non-Hodgkin's lymphomas: Meta-analysis of epidemiology data and therapy options. World J Hepatol 2016;8:107-16.

Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 2011;31:61-80.

Tucci F, Küppers R. Role of hepatitis C virus in B cell lymphoproliferations. Virol Sin 2014;29:3-6.

Dammacco F, Sansonno D, Piccoli C, Racanelli VD'Amore FP, Lauletta G. The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and Overt B-cell malignancy. Semin Liver Dis 2000;20:143-57.

Ferri C, Caracciolo F, Zignego AL, La Civita L, Monti M, Longombardo G, et al. Hepatitis C virus infection in patients with non-Hodgkin’s lymphoma. Br J Haematol 1994;88:392-4.

Quinn E, Chan C, Hadlock K, Foung S, Flint M, Levy S. The B-cell receptor of a hepatitis C virus (HCV)- associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis Blood 2001;98:3745-9.

Varma S, Menon MC, Garg A, Malhotra P, Sharma A, Chawla YK, Dhiman RK. Hepatitis C virus infection among patients with non-Hodgkin’s lymphoma in northern India. Hepatol Int 2011;5:688-92.

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-56.

Swerdlow S, Campo E, Pileri S, Harris N, Stein H, Siebert R, Advani R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.

Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61:77- 87.

Mousa SM. Hepatitis C among Egyptian Patients Referred for Bone Marrow Examination: Seroprevalence and Analysis of Hematological Findings. Bone Marrow Res 2014;2014:549716.

Abu-Taleb F, El-Hefni A, Kotb A, El-Gohary TA. Efficacy of ribavirin to prevent hepatitis reactivation in hepatitis C virus-infected patients treated for nonHodgkin lymphoma. Afro-Egypt J Infect Endem Dis 2013;3:17-26.

Cowgill KD, Loffredo CA, Eissa SA, Mokhtar N, AbdelHamid M, Fahmy A, Strickland GT. Case-control study of non-Hodgkin’s lymphoma and hepatitis C virus infection in Egypt. Int J Epidemiol 2004;33:1034-9.

Gisbert JP, García-Buey L, Pajares JM, Moreno-Otero R. Prevalence of hepatitis C virus infection in B-cell nonHodgkin's lymphoma: systematic review and metaanalysis. Gastroenterology 2003;125:1723-32.

Miller FD and Abu-Raddad LJ. Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt. Proc Natl Acad Sci USA 2010;107:14757-62.

Torres HA and Mahale P. Most patients with HCVassociated lymphoma present with mild liver disease: a call to revise antiviral treatment prioritization. Liver Int 2015;35:1661-4.

Goldman L, Ezzat S, Mokhtar N, Abdel-Hamid A, Fowler N, Gouda I, et al. Viral and non-viral risk factors for nonHodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes. Cancer Causes Control 2009;20:981-7.

Libra M, Polesel J, Russo AE, De Re V, Cina D, Serraino D, et al. Extrahepatic disorders of HCV infection: a distinct entity of B-cell neoplasia? Int J Oncol 2010;36:1331-40.

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

Nieters A, Kallinowski B, Brennan P, Ott M, Maynadie M, Benavente Y, et al. Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology 2006;131:1879-86.

Ferri C, Greco F, Longombardo G, Palla P, Moretti A, Marzo E, et al. Association between hepatitis C virus and mixed cryoglobulinemia. Clin Exp Rheumatol 1991;9:621-4.

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

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

Stefanova-Petrova DV, Tzvetanska AH, Naumova EJ, Mihailova AP, Hadjiev EA, Dikova RP, et al. Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J Gastroenterol 2007;13:6518- 8

Hamdy HS, Abdelkader NA, Mansour A, Allam EH, ElWakiel HM, Elshenawy D. B cell non-Hodgkin's lymphoma in chronic hepatitis C virus patients: An interesting relationship. Indian J Gastroenterol. 2015;34:127-34.

Louie KS, Micallef JM, Pimenta JM, Forssen UM. Prevalence of thrombocytopenia among patients with chronic hepatitis C: A systematic review. J Viral Hepat 2011;18:1-7.

Weksler BB. Review article: the pathophysiology of thrombocytopenia in hepatitis C virus infection and chronic liver disease. Aliment Pharmacol Ther2007;26:13-9.

Huckans M, Fuller BE, Chalker A, Adams M, Loftis J. Plasma inflammatory Factors are associated with anxiety, Depression, and cognitive Problems in adults with and without Methamphetamine Dependence: an exploratory Protein array study. Front Psychiatr 2015;6;178.

Sung VM, Shimodaira S, Doughty AL, Picchio GR, Can H, Yen TS, et al. Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J Virol 2003;77:2134-46.

Fisher S, Fisher R. The epidemiology of non-Hodgkin's lymphoma. Oncogene 2004;23;6524-34.

Ciufu C, Arama V, Bumbea H, Dobrea C, Ion I, Vladareanu AM. Correlations of hematological parameters with bone marrow findings in chronic lymphoproliferative disorders associated with hepatitis viruses. J Med Life 2013;6:464-71.

Youssef S, Nasr A, El Zanaty T, El Rawi RS, Mattar MM. Prevalence of occult hepatitis C virus in Egyptian patients with chronic lymphoproliferative Disorders. Hepat Res Treat 2012;2012:42978.

Talamini R, Montella M, Crovatto M, Dal Maso L, Crispo A, Negri E, et al. non-Hodgkin’s lymphoma and hepatitis C virus: A case-control study from northern and southern Italy. Int J Cancer 2004;110:380-5.

Salem AK. Prevalence of HCV among Yemeni patients with non-Hodgkin’s lymphoma at AI-Thawra teaching hospital. Gulf J Oncolog 2009;5:22-9.

Caviglia GP, Sciacca C, Abate ML, Olivero A, Rosso C, Touscoz GA, et al. Chronic hepatitis C virus infection and lymphoproliferative disorders: mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma. J Gastroenterol Hepatol 2015;30:742-7.

Onyekwere CA, O Ogbera A, Olusola Dada A, Adeleye, Dosunmu A, Akinbami AA, et al. Hepatitis C Virus (HCV) Prevalence in Special Populations and Associated Risk Factors: A Report From a Tertiary Hospital. Hepat Mon 2016;16:e35532.

Rastin M, Khoee AR, Tabasi N, Sheikh A, Ziaolhagh S, Esmaeeli E, et al. Evaluation of HTLV-I and HCV Prevalence in Non-Hodgkin's Lymphoma. Iran J Basic Med Sci 2013;16:242-6.

Engels EA, Chatterjee N, Cerhan JR, Davis S, Cozen W, Severson RK, et al. Hepatitis C virus infection and nonHodgkin lymphoma: results of the NCI-SEER multicenter case-control study. Int J Cancer 2004;111:76-80.

Sonmez M, Bektas O, Yilmaz M, Durmus A, Akdogan E, Topbas M, et al. The relation of lymphoma and hepatitis B virus/hepatitis C virus infections in the region of East Black Sea, Turkey. Tumori 2007;93:536-9.

Spinelli JJ, Lai AS, Krajden M, Andonov A, Gascoyne RD, Connors JM, et al. Hepatitis C virus and risk of nonHodgkin lymphoma in British Columbia, Canada. Int J Cancer 2008;122:630-3.

Schöllkopf C, Smedby KE, Hjalgrim H, Rostgaard K, Panum I, Vinner L, et al. Hepatitis C infection and risk of malignant lymphoma. Int J Cancer 2008;122:1885-90.

Park SC, Jeong SH, Kim J, Han CJ, Kim YC, Choi KS, et al. High prevalence of hepatitis B virus infection in patients with B cell non-Hodgkin’s lymphoma in Korea. J Med Virol 2008;80:960-6.

Varma S, Menon MC, Garg A, Malhotra P, Sharma A, Chawla YK, et al. Hepatitis C virus infection among patients with non-Hodgkin's lymphoma in northern India. Hepatol Int. 2011;5:688-92.


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