Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab

J Clin Oncol. 2009 Feb 1;27(4):605-11. doi: 10.1200/JCO.2008.18.0182. Epub 2008 Dec 15.


Purpose: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab.

Patients and methods: Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy.

Results: Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation.

Conclusion: Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / analysis
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Rituximab
  • Vincristine / therapeutic use
  • Virus Activation*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Hepatitis B Surface Antigens
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone

Supplementary concepts

  • VAP-cyclo protocol