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Hepatitis B and C Virus Reactivation Patterns in a Romanian Cohort of Patients with Chronic Lymphoproliferative Disorders

  • Violeta MolagicEmail author
  • Raluca Mihailescu
  • Catalin Tiliscan
  • Cristina Popescu
  • Ana Maria Vladareanu
  • Remulus Catana
  • Mihaela Radulescu
  • Victoria Arama
  • Stefan Sorin Arama
Original Article
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Abstract

Hepatitis B and C virus (HBV and HCV) reactivations have become more common following the intensive use of biological therapies for the treatment of chronic lymphoproliferative disorders (CLD). We evaluate risk factors for virus reactivation and exitus in patients diagnosed with CLD and HBV or HCV infection, undergoing rituximab-chemotherapy (R-chemo). A prospective, observational study in two tertiary-care Romanian hospitals, between December 2007 and May 2010, of patients diagnosed with CLD undergoing R-chemo. HBV and HCV serological markers, viral load, fibrosis and necroinflammation were assessed at baseline and every 3–6 months. We screened 502 patients diagnosed with CLDs (77.2% non-Hodgkin lymphomas) and enrolled 57 patients with HBV and/or HCV infection with a mean age of 61.35 ± 11.1 years. The replicative virus was HBV in 23 patients (40.3%), HCV in 33 patients (57.9%). HCV reactivation rate (15.6%) was lower than for HBV (45.5%) (p = 0.02). In univariate analysis, viral reactivation was associated with aggressive CLD (p = 0.01), HBV (p = 0.01) and lymphopenia (p = 0.02). Death was associated with aggressive CLD (p = 0.01), viral reactivation (p = 0.001) and high baseline viremia (p = 0.05). In multivariate analysis, viral reactivation was associated with lymphopenia (OR 0.05, 95% CI 0.003–0.85, p = 0.03). Risk of death was 10 times higher for patients with viral reactivation (95% CI 1.54–65.5, p = 0.01). A quarter of the infected patients were diagnosed with viral reactivation. While hepatitis C was more prevalent than hepatitis B in patients with CLD, viral reactivation was found 3 times more frequently in patients with hepatitis B than C.

Keywords

Lymphoproliferative disorders Hepatitis B virus reactivation Hepatitis C virus reactivation Biological therapies 

Abbreviations

HBV

Hepatitis B virus

HCV

Hepatitis C virus

CLD

Chronic lymphoproliferative disorder

NHL

Non-Hodgkin lymphoma

CHB

Chronic hepatitis B

CHC

Chronic hepatitis C

R-chemo

Rituximab-chemotherapy

Notes

Funding

The current study belongs to a national Grant PNCDI-II/41-012/2007, known as LIMFO-VIR.

Authors’ Contribution

All authors had equal contributions in writing this paper.

Conflict of interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Ethical Standard

This study was approved by the Ethics Committee of the National Institute for Infectious Diseases “Prof. Dr. Matei Balş” and the University Emergency Hospital Bucharest, Bucharest, Romania.

References

  1. 1.
    Popovici O, Molnar G, Janta D (2014) Rezultatele studiului sero-epidemiologic de prevalenta pentru infectia cu virus hepatitic B si virus hepatitic C. In: National conference of microbiology and epidemiology (Conferinta Nationala de Microbiologie si Epidemiologie), Bucharest, 13–15 November 2014Google Scholar
  2. 2.
    Dal Maso L, Franceschi S (2006) Hepatitis C virus and risk of lymphoma and other lymphoid neoplasms: a meta-analysis of epidemiologic studies. Cancer Epidemiol Biomark Prev 15:2078–2085CrossRefGoogle Scholar
  3. 3.
    Nath A, Agarwal R, Malhotra P, Varma S (2010) Prevalence of hepatitis B virus infection in non-Hodgkin’s lymphoma: a systematic review and meta-analysis. Intern Med J 40:633–641CrossRefGoogle Scholar
  4. 4.
    Marcucci F, Mele A (2011) Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis and therapeutic opportunities. Blood 117(6):1792–1798CrossRefGoogle Scholar
  5. 5.
    American Association for the Study of liver diseases emerging trends conference, Reactivation of Hepatitis B, Arlington: March 21–22, 2013Google Scholar
  6. 6.
    Harris NE, Jaffe ES, Stein H (1994) A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392Google Scholar
  7. 7.
    Harris NL (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997. Ann Oncol 10:1419–1432CrossRefGoogle Scholar
  8. 8.
    Swerldlow SH, Campo E, Harris NL (2008) In: WHO classification of tumours of haematopietic and lymphoid tissues. International Agency for Research in Cancer/IACRS Press, LyonGoogle Scholar
  9. 9.
    Porter RS, Kaplan JL (2011) Neutropenia and lymphocytopenia, chap 107. In: Merck manual of diagnosis and therapy, 19th edn. Merck Sharp Dohme Corp., Whitehouse StationGoogle Scholar
  10. 10.
    Kawsar Hameem I, Shahnewaz J, Gopalakrishna KV, Spiro TP, Daw HA (2012) Role of prechemotherapy screening and antiviral prophylaxis. Clin Adv Hematol Oncol 10(6):370–378Google Scholar
  11. 11.
    Nosotti L, D’Andrea M, Pitidis A (2012) Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin’s lymphoma patients treated with immunochemotherapy. Scand J Infect Dis 44:70–73CrossRefGoogle Scholar
  12. 12.
    Yeo W, Chan PK, Zhong S, Ho WM, Steinberg JL, Tam JS et al (2000) Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol 62(3):299–307CrossRefGoogle Scholar
  13. 13.
    Yang F, Zhu HL, He C, Li JJ, Xiang B, Cui X et al (2014) Effect of antiviral prophylaxis strategy for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma patients with hepatitis B virus infection: a retrospective cohort study. Indian J Hematol Blood Transfus 30(2):97–104CrossRefGoogle Scholar
  14. 14.
    Loomba R, Rowley A, Wesley R, Liang TJ, Hoofnagle JH, Pucino F et al (2008) Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 148(7):519–528CrossRefGoogle Scholar
  15. 15.
    Yeo W, Johnson P (2006) Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology 43(2):209–220CrossRefGoogle Scholar
  16. 16.
    Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D (1991) Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology 100:182–188CrossRefGoogle Scholar
  17. 17.
    Drugan C, Brichler S, Muntean M, Olteanu I, Carstina D, Drugan T et al (2008) Genotipe of hepatitis B virus in Romanian patients. Appl Med Inform 22(1–2):27–32Google Scholar
  18. 18.
    Constantinescu I, Dinu AA, Boscaiu V, Niculescu M (2014) Hepatitis B virus core promoter mutations in patients with chronic hepatitis B and hepatocellular carcinoma in Bucharest, Romania. Hepat Mon 14(10):e22072CrossRefGoogle Scholar
  19. 19.
    Carman WF, Fagan EA, Hadziyannis S, Karayiannis P, Tassopoulos NC, Williams R (1991) Association of a precore genomic variant of HBV with fulminant hepatitis. Hepatology 14(2):219–222CrossRefGoogle Scholar
  20. 20.
    Yeo W, Zhong S, Chan PKS, Ho WM, Wong HTM, Chan ASK (2000) Sequence variations of precore/core and precore promoter regions of hepatitis B virus in patients with or without viral reactivation during cytotoxic chemotherapy. J Viral Hepat 7:448–458CrossRefGoogle Scholar
  21. 21.
    Nagamatsu H, Kumashiro R, Itano S, Matsugaki S, Sata M (2003) Investigation of associating factors in exacerbation of liver damage after chemotherapy in patients with HBV-related HCC. Hepatol Res 26:293–301CrossRefGoogle Scholar
  22. 22.
    Cheng AL, Hsiung CA, Su IJ, Chang MC, Tsao CJ, Kao WY et al (2003) Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Hepatology 37:1320–1328CrossRefGoogle Scholar
  23. 23.
    Markovic S, Drozina G, Vovk M, Fidler-Jenko M (1999) Reactivation of hepatitis B but not hepatitis C in patients with malignant lymphoma and immunosuppressive therapy. A prospective study in 305 patients. Hepatogastroenterology 46(29):2925–2930Google Scholar
  24. 24.
    Liang R, Lau GK, Kwong YL (1999) Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriers: a review of the problem. J Clin Oncol 17:394–398CrossRefGoogle Scholar
  25. 25.
    Lee GW, Ryu MH, Lee JL, Oh S, Kime E, Lee JH et al (2003) The prophylactic use of lamivudine can maintain dose-intensity of adriamycin in hepatitis-B surface antigen (HBs Ag)-positive patients with non-Hodgkin’s lymphoma who receive cytotoxic chemotherapy. J Korean Med Sci 18:849–854CrossRefGoogle Scholar
  26. 26.
    Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY et al (2006) Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 131:59–68CrossRefGoogle Scholar
  27. 27.
    Vento S, Cainelli F, Mirandola F, Cosco L, Di Perri G, Solbiati M et al (1996) Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus. Lancet 347:92–93CrossRefGoogle Scholar
  28. 28.
    Lim R, Holt A (2014) Hepatitis B and C prophylaxis in patients receiving chemotherapy. Viral Hepat Pract 6(1):10–13Google Scholar
  29. 29.
    Faggioli P, De Paschale M, Tocci A, Luoni M, Fava S, De Paoli A et al (1997) Acute hepatic toxicity during cyclic chemotherapy in non Hodgkin’s lymphoma. Haematologica 82:38–42Google Scholar
  30. 30.
    Torres HA, Davila M (2012) Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol 9:156–166CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  • Violeta Molagic
    • 1
    Email author
  • Raluca Mihailescu
    • 1
  • Catalin Tiliscan
    • 1
    • 2
  • Cristina Popescu
    • 1
    • 2
  • Ana Maria Vladareanu
    • 2
    • 3
  • Remulus Catana
    • 1
  • Mihaela Radulescu
    • 1
    • 2
  • Victoria Arama
    • 1
    • 2
  • Stefan Sorin Arama
    • 2
  1. 1.National Institute for Infectious Diseases “Prof. Dr. Matei Balş”BucharestRomania
  2. 2.Carol Davila University of Medicine and PharmacyBucharestRomania
  3. 3.Department of HematologyUniversity Emergency Hospital BucharestBucharestRomania

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