Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study

Clin Infect Dis. 2015 Sep 1;61(5):719-29. doi: 10.1093/cid/civ344. Epub 2015 May 1.


Background: There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs).

Methods: We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL.

Results: With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis.

Conclusions: Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

Keywords: HBV DNA monitoring; HBV reactivation; preemptive antiviral therapy; resolved HBV infection; rituximab.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • DNA, Viral / blood*
  • Female
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B / epidemiology
  • Hepatitis B / virology*
  • Hepatitis B virus / genetics*
  • Humans
  • Lymphoma, B-Cell / complications*
  • Lymphoma, B-Cell / epidemiology
  • Lymphoma, B-Cell / virology
  • Male
  • Middle Aged
  • Prospective Studies


  • Antiviral Agents
  • DNA, Viral

Associated data

  • JPRN/UMIN000001299