Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study

J Clin Oncol. 2014 Nov 20;32(33):3736-43. doi: 10.1200/JCO.2014.56.7081. Epub 2014 Oct 6.


Purpose: Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described.

Patients and methods: HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.

Results: Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.

Conclusion: A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • DNA, Viral / analysis
  • Female
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology*
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / virology
  • Male
  • Middle Aged
  • Prospective Studies
  • Rituximab
  • Virus Activation*


  • Antibodies, Monoclonal, Murine-Derived
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Rituximab