High Rate of Hepatitis B Reactivation in Chinese Patients Receiving Rituximab for Lymphoma


Key Points

  • The 2-year HBV reactivation rate was 41.5% in Chinese patients receiving rituximab for lymphoma.
  • Undetectable antibody to HBsAg at baseline was a significant predictor of reactivation.

In a prospective Chinese study reported in the Journal of Clinical Oncology, Seto et al found a 2-year rate of hepatitis B virus (HBV) reactivation of 41.5% in hepatitis B surface antigen (HBsAg)-negative and anti–hepatitis B core antigen antibody (anti-HBc)–positive patients receiving rituximab (Rituxan)-containing chemotherapy for lymphoma.

Study Details

The study included 260 HBsAg-negative and anti-HBc–positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL) receiving rituximab-containing chemotherapy who were monitored every 4 weeks for up to 2 years. Entecavir treatment was started when patients exhibited HBV reactivation defined as detectable HBV DNA. Among the 260 patients, 63 patients (24.2%) were HBsAg-negative and anti-HBc–positive.

Reactivation Rate and Risk

Median follow-up was 70 weeks (range = 6–104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%. Reactivation occurred at a median of 23 weeks (range = 4–100 weeks) after rituximab treatment, and median HBV DNA level at reactivation was 43 IU/mL (range = 14–920 IU/mL). Baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only risk factor significantly associated with HBV reactivation (hazard ratio = 3.51, P = .009). Two-year cumulative reactivation rates were 68.3% in patients negative at baseline for anti-HBs vs 34.4% in those positive at baseline (P = .012).

All patients had normal ALT and all but one was HBsAg-negative at reactivation. Entecavir treatment controlled HBV reactivation in all patients.

The investigators concluded: “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.”

Man-Fung Yuen, MD, of The University of Hong Kong, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by The University of Hong Kong. For full disclosures of the study authors, visit

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