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Hepatitis B virus reactivation in hepatitis B surface antigen seropositive patients with metastatic non-small cell lung cancer receiving cytotoxic chemotherapy: the efficacy of preemptive lamivudine and identification of risk factors

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Abstract

Little is known about the likelihood and degree of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) seropositive patients with disseminated non-small cell lung cancer (NSCLC) receiving chemotherapy. Between January 2003 and December 2013, all HBsAg seropositive patients with metastatic NSCLC receiving cytotoxic chemotherapy were retrospectively evaluated. The morbidity and mortality of HBV reactivation, risk factors associated with reactivation, as well as the efficacy of preemptive lamivudine were investigated. Of 258 patients who were eligible for the present study, 176 were treated without antiviral prophylaxis and 82 received preemptive lamivudine. Patients without lamivudine prophylaxis had a significantly higher prevalence of HBV reactivation (19.3 vs 6.1 %, p = 0.006) and severe hepatitis attributable to reactivation (11.8 vs 3.7 %, p = 0.034) than those with preemptive lamivudine. However, no significant difference in mortality due to reactivation was noted between patients with or without prophylactic lamivudine (0 vs 2.3 %, p = 0.310). Furthermore, patients who developed HBV reactivation were indentified to have a higher rate of HBeAg seropositivity (74.4 vs 43.4 %, p < 0.001), serum HBV-DNA level of 104 copies/ml or greater (76.9 vs 47.9 %, p = 0.001), coexisting liver metastasis (50.0 vs 40.6 %, p = 0.033) and treatment with more than 4 cycles of chemotherapy (56.4 vs 39.3 %, p = 0.046) than those who did not experienced reactivation. The current study has demonstrated that preemptive lamivudine significantly reduced the prevalence of HBV reactivation in HBsAg seropositive patients with metastatic NSCLC receiving systemic chemotherapy.

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References

  1. Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45(2):507–39.

    Article  CAS  PubMed  Google Scholar 

  2. Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49(S5):S156–65.

    Article  CAS  PubMed  Google Scholar 

  3. Xunrong L, Yan AW, Liang R, Lau GK. Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy—pathogenesis and management. Rev Med Virol. 2001;11(5):287–99.

    Article  CAS  PubMed  Google Scholar 

  4. Ozguroglu M, Bilici A, Turna H, Serdengecti S. Reactivation of hepatitis B virus infection with cytotoxic therapy in non-Hodgkin’s lymphoma. Med Oncol. 2004;21(1):67–72.

    Article  CAS  PubMed  Google Scholar 

  5. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661–2.

    Article  PubMed  Google Scholar 

  6. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92–8.

    Article  CAS  PubMed  Google Scholar 

  7. Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol. 2005;23(1):190–6.

    Article  CAS  PubMed  Google Scholar 

  8. Yeo W, Johnson PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology. 2006;43(2):209–20.

    Article  CAS  PubMed  Google Scholar 

  9. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.

    Article  CAS  PubMed  Google Scholar 

  10. Horvath J, Raffanti SP. Clinical aspects of the interactions between human immunodeficiency virus and the hepatotropic viruses. Clin Infect Dis. 1994;18(3):339–47.

    Article  CAS  PubMed  Google Scholar 

  11. Mondelli M, Vergani GM, Alberti A, et al. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982;129(6):2773–8.

    CAS  PubMed  Google Scholar 

  12. Lau GK, Liang R, Chiu EK, Lee CK, Lam SK. Hepatic events after bone marrow transplantation in patients with hepatitis B infection: a case controlled study. Bone Marrow Transplant. 1997;19(8):795–9.

    Article  CAS  PubMed  Google Scholar 

  13. Chen XQ, Peng JW, Lin GN, Li M, Xia ZJ. The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy. Med Oncol. 2012;29(2):1237–41.

    Article  PubMed  Google Scholar 

  14. Dai MS, Wu PF, Shyu RY, Lu JJ, Chao TY. Hepatitis B virus reactivation in breast cancer patients undergoing cytotoxic chemotherapy and the role of preemptive lamivudine administration. Liver Int. 2004;24(6):540–6.

    Article  CAS  PubMed  Google Scholar 

  15. Yeo W, Hui EP, Chan AT, et al. Prevention of hepatitis B virus reactivation in patients with nasopharyngeal carcinoma with lamivudine. Am J Clin Oncol. 2005;28(4):379–84.

    Article  PubMed  Google Scholar 

  16. Huang H, Cai Q, Lin T, et al. Lamivudine for the prevention of hepatitis B virus reactivation after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with advanced or relapsed non-Hodgkin’s lymphoma single institution experience. Expert Opin Pharmacother. 2009;10(15):2399–406.

    Article  CAS  PubMed  Google Scholar 

  17. Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148(7):519–28.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Hsu C, Hsiung CA, Su IJ, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin’s lymphoma: a randomized trial. Hepatology. 2008;47(3):844–53.

    Article  CAS  PubMed  Google Scholar 

  19. Eren OO, Artac M, Boruban MC, Yavas O, Arslan U, Basaranoglu M. Chemotherapy-induced hepatitis B virus reactivation in HbsAg positive cancer patients: a single center experience. Med Oncol. 2009;26(4):386–92.

    Article  CAS  PubMed  Google Scholar 

  20. Ziakas PD, Karsaliakos P, Mylonakis E. Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance. Haematologica. 2009;94(7):998–1005.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Shikata T, Karasawa T, Abe K, et al. Hepatitis B e antigen and infectivity of hepatitis B virus. J Infect Dis. 1977;136(4):571–6.

    Article  CAS  PubMed  Google Scholar 

  22. Jang JW, Choi JY, Bae SH, et al. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma. J Hepatol. 2004;41(3):427–35.

    Article  CAS  PubMed  Google Scholar 

  23. Lau GK, Leung YH, Fong DY, et al. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood. 2002;99(7):2324–30.

    Article  CAS  PubMed  Google Scholar 

  24. Zhong S, Yeo W, Schroder C, Chan P, Wong W, Ho WM, et al. High hepatitis B virus (HBV) DNA viral load is an important risk factor for HBV reactivation in breast cancer patients undergoing cytotoxic chemotherapy. J Viral Hepat. 2004;11(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  25. Yeo W, Chan PK, Zhong S, et al. 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. 2000;62(3):299–307.

    Article  CAS  PubMed  Google Scholar 

  26. Yeo W, Chan PK, Ho WM, et al. Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. J Clin Oncol. 2004;22(5):927–34.

    Article  CAS  PubMed  Google Scholar 

  27. Lau GK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int. 2008;2(2):152–62.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol. 2014;11(4):209–19.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Zhong-Jun Xia.

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Lin, GN., Peng, JW., Xiao, Jj. et al. Hepatitis B virus reactivation in hepatitis B surface antigen seropositive patients with metastatic non-small cell lung cancer receiving cytotoxic chemotherapy: the efficacy of preemptive lamivudine and identification of risk factors. Med Oncol 31, 119 (2014). https://doi.org/10.1007/s12032-014-0119-0

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