The hepatitis B virus (HBV) is a major global issue, because an increased risk of hepatocellular carcinoma among patients infected with HBV is well established. Recently, it has been suggested that HBV is associated with other human cancers. However, the association between HBV and the risk of onset of hematological malignancies remains controversial. The aim of this large-scale retrospective cohort study was to evaluate the association between HBV infection and hematological malignancies. A retrospective analysis of 86,115 newly admitted patients at Shanghai Ruijin Hospital was performed. A cohort of patients previously exposed to HBV (n = 1,874) and a cohort of individuals without a positive test for anti-hepatitis B core antigen (anti-HBc; n = 45,118) were compared to assess the risk of hematological malignancies. Anti-HBc was positive in 61.2% cases and 54.3% controls (p = 0.0001). The risk of B cell non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and multiple myeloma was higher in the HBV-infected cohort than in the non-HBV-infected cohort. In conclusion, patients infected with HBV have a substantially increased risk of hematological malignancies.

Keywords:
Hematological malignancy, Hepatitis B virus, Morbidity
1.
Wedemeyer H, Manns MP: Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol 2010;7:31-40.
2.
Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD: Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008;14:4300-4308.
3.
Liao B, Zhang F, Lin S, He H, Liu Y, Zhang J, Xu Y, Yi J, Chen Y, Liu H, Wang Z, Cai W: Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective cross-sectional study in Guangdong, China. PLoS One 2014;9:e115888.
4.
Andersen ES, Omland LH, Jepsen P, Krarup H, Christensen PB, Obel N, Weis N; DANVIR Cohort Study: Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus. J Viral Hepat 2015;22:828-834.
5.
Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y: Epidemiological serosurvey of hepatitis B in China: declining HBV prevalence due to hepatitis B vaccination. Vaccine 2009;27:6550-6557.
6.
Lu FM, Zhuang H: Management of hepatitis B in China. Chin Med J 2009;122:3-4.
7.
Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V; WHO International Agency for Research on Cancer Monograph Working Group: A review of human carcinogens. Part B: biological agents. Lancet Oncol 2009;10:321-322.
8.
de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, Plummer M: Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012;13:607-615.
9.
Luppi M, Torelli G: The new lymphotropic herpes viruses (HHV-6, HHV-7, HHV-8) and hepatitis C virus (HCV) in human lymphoproliferative diseases: an overview. Haematologica 1996;81:265-281.
10.
Ito K, Arai M, Imazeki F, Yonemitsu Y, Bekku D, Kanda T, Fujiwara K, Fukai K, Sato K, Itoga S, Nomura F, Yokosuka O: Risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol 2010;45:243-249.
11.
Hassan MM, Li D, El-Deeb AS, Wolff RA, Bondy ML, Davila M, Abbruzzese JL: Association between hepatitis B virus and pancreatic cancer. J Clin Oncol 2008;26:4557-4562.
12.
Bronowicki JP, Loriot MA, Thiers V, Grignon Y, Zignego AL, Bréchot C: Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice. Hepatology 1998;28:211-218.
13.
Lok AS, McMahon BJ: Chronic hepatitis B. Hepatology 2007;45:507-539.
14.
Lee WM: Hepatitis B virus infection. N Engl J Med 1997;337:1733-1745.
15.
Qiu Q, Li Y, Duan XW, Yang LK, Chen Y, Li H, Wang L, Duan ZP: Impact of a new reimbursement program on hepatitis B antiviral medication cost and utilization in Beijing, China. PLoS One 2014;9:e109652.
16.
Marcucci F, Mele A, Spada E, Candido A, Bianco E, Pulsoni A, Chionne P, Madonna E, Cotichini R, Barbui A, De Renzo A, Dore F, Iannitto E, Liso V, Martino B, Montanaro M, Pagano L, Musto P, Rapicetta M: High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma. Haematologica 2006;91:554-557.
17.
Franceschi S, Lise M, Trépo C, Berthillon P, Chuang SC, Nieters A, Travis RC, Vermeulen R, Overvad K, Tjønneland A, Olsen A, Bergmann MM, Boeing H, Kaaks R, Becker N, Trichopoulou A, Lagiou P, Bamia C, Palli D, Sieri S, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Peeters PH, Rodríguez L, Barroso LL, Dorronsoro M, Sánchez MJ, Navarro C, Barricarte A, Regnér S, Borgquist S, Melin B, Hallmans G, Khaw KT, Wareham N, Rinaldi S, Hainaut P, Riboli E, Vineis P: Infection with Hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Epidemiol Biomarkers Prev 2011;20:208-214.
18.
Anderson LA, Pfeiffer R, Warren JL, Landgren O, Gadalla S, Berndt SI, Ricker W, Parsons R, Wheeler W, Engels EA: Hematopoietic malignancies associated with viral and alcoholic hepatitis. Cancer Epidemiol Biomark Prev 2008;17:3069-3075.
19.
Muñoz SJ: Use of hepatitis B core antibody-positive donors for liver transplantation. Liver Transpl 2002;8(suppl 1):S82-S87.
20.
Fukuda R, Ishimura N, Niigaki M, Hamamoto S, Satoh S, Tanaka S, Kushiyama Y, Uchida Y, Ihihara S, Akagi S, Watanabe M, Kinoshita Y: Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance. J Med Virol 1999;58:201-207.
21.
Paterlini P, Driss F, Nalpas B, Pisi E, Franco D, Berthelot P, Bréchot C: Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area. Hepatology 1993;17:20-29.
22.
Bréchot C: Hepatitis B virus (HBV) and hepatocellular carcinoma: HBV DNA status and its implications. J Hepatol 1987;4:269-279.
23.
Zemel R, Issachar A, Tur-Kaspa R: The role of oncogenic viruses in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis 2011;15:261-279.
24.
Martin-Vilchez S, Lara-Pezzi E, Trapero-Marugán M, Moreno-Otero R, Sanz-Cameno P: The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection. Rev Med Virol 2011;21:315-329.
25.
Yoo YG, Oh SH, Park ES, Cho H, Lee N, Park H, Kim DK, Yu DY, Seong JK, Lee MO: Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1alpha through activation of mitogen-activated protein kinase pathway. J Biol Chem 2003;278:39076-39084.
26.
Kang J, Cho JH, Suh CW, Lee DH, Oh HB, Sohn YH, Chi HS, Park CJ, Jang SS, Lee KH, Lee JH, Lee JH, Lee SW, Chung YH, Kim TH, Shin HR, Huh J: High prevalence of hepatitis B and hepatitis C virus infections in Korean patients with hematopoietic malignancies. Ann Hematol 2011;90:159-164.
27.
Seto WK, Chan TS, Hwang YY, Wong DK, Fung J, Liu KS, Gill H, Lam YF, Lie AK, Lai CL, Kwong YL, Yuen MF: Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol 2014;32:3736-3743.
28.
Pattullo V: Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure. World J Hepatol 2015;7:954-967.
29.
Wei Z, Zou S, Li F, Cheng Z, Li J, Wang J, Wang C, Chen F, Cao J, Cheng Y: HBsAg is an independent prognostic factor in diffuse large B cell lymphoma patients in rituximab era: result from a multicenter retrospective analysis in China. Med Oncol 2014;31:845.
30.
Huang H, Li X, Zhu J, Ye S, Zhang H, Wang W, Wu X, Peng J, Xu B, Lin Y, Cao Y, Li H, Lin S, Liu Q, Lin T: Entecavir versus lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA 2014;312:2521-2530.
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2017
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