, Volume 47, Issue 2, pp 313–316 | Cite as

Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report

  • Arturo CicculloEmail author
  • F. R. Ponziani
  • E. Maiolo
  • F. Pallavicini
  • M. Pompili
Case Report



Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen.

Case Presentation

We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed.


Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.


Hepatitis B Lymphoma Entecavir Rituximab 



This manuscript was not funded.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    Marzano A, Bruno R, Fagiuoli S, et al. Gestione Clinica della Epatite B negli immunocompromessi: aggiornamento italiano 2017. Documento AISF. 2017.Google Scholar
  2. 2.
    Coluccio C, Begini P, Marzano A, Pellicelli A, Imperatrice B, Anania G, Delle Fave G, Marignani M. Hepatitis B in patients with hematological diseases: an update. World J Hepatol. 2017;9:1043–53.CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Yeo W, Chan TC, Leung NW, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11. Scholar
  4. 4.
    Koo YX, Tay M, Teh YE, et al. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis. Ann Hematol. 2011;90:1219–23. Scholar
  5. 5.
    Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:215–9. (quiz e16–7).CrossRefGoogle Scholar
  6. 6.
    Lok ASF, Liang RHS, Chiu EKW, et al. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study. Gastroenterology. 2001;100:182–8.CrossRefGoogle Scholar
  7. 7.
    Mélet J, Mulleman D, Goupille P, et al. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum. 2013;65:2783–90. Scholar
  8. 8.
    European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98. Scholar
  9. 9.
    Viganò M, Serra G, Casella G, et al. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders. Expert Opin Biol Ther. 2016;16:917–26. Scholar
  10. 10.
    Li H, Zhang HM, Chen LF, et al. Prophylactic lamivudine to improve the outcome of HBsAgpositive lymphoma patients during chemotherapy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2015.Google Scholar
  11. 11.
    Li HR, Huang JJ, Guo HQ, et al. Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy. J Viral Hepat. 2011;18:877–83.CrossRefGoogle Scholar
  12. 12.
    Huang H, Li X, Zhu J, Ye S. Entecavir vs 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;312:2521–30.CrossRefGoogle Scholar
  13. 13.
    Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol. 2007;136:699–712 (Review. Erratum in: Br J Haematol. 2007 Apr;137(1):81).CrossRefGoogle Scholar
  14. 14.
    Pattullo V. Prevention of Hepatitis B reactivation in the setting of immunosuppression. Clin Mol Hepatol. 2016;22:219–37.CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Matsue K, Kimura S, Takanashi Y, et al. Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Cancer. 2010;116:4769–76. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Clinical Infectious DiseasesCatholic University of the Sacred HeartRomeItaly
  2. 2.Internal Medicine, Gastroenterology and Hepatology UnitFondazione Agostino Gemelli Hospital, Catholic UniversityRomeItaly
  3. 3.Institute of HematologyUniversità Cattolica del Sacro CuoreRomeItaly

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