Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection

J Hepatol. 2018 Aug;69(2):286-292. doi: 10.1016/j.jhep.2018.02.033. Epub 2018 Mar 16.


Background & aims: Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation.

Methods: We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation.

Results: HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92-76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15-5.05; p = 0.02).

Conclusions: Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients.

Lay summary: In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229.

Keywords: Anti-core antibody; Chemotherapy; Entecavir; Prophylactic antiviral therapy; Resolved hepatitis B infection; Rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • DNA, Viral / blood
  • Female
  • Hepatitis B Antibodies / blood*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / physiology*
  • Hepatitis B* / complications
  • Hepatitis B* / drug therapy
  • Hepatitis B* / immunology
  • Humans
  • Lymphoma, Non-Hodgkin* / complications
  • Lymphoma, Non-Hodgkin* / drug therapy
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Assessment / methods
  • Rituximab / therapeutic use*
  • Taiwan
  • Virus Activation / immunology*


  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Rituximab