Reactivation of hepatitis B virus after rituximab‐containing treatment in patients with CD20‐positive B‐cell lymphoma

BACKGROUND: Reactivation of hepatitis B virus (HBV) after rituximab‐containing chemotherapy in patients with B‐cell lymphoma has been recognized as a potentially serious complication in HBV immune patients. METHODS: To determine the HBV reactivation in patients treated with rituximab, a retrospective study of HBV‐related markers was performed before and after rituximab‐containing treatment in 261 consecutive patients with CD20‐positive B‐cell lymphoma. RESULTS: Of the 261 patients, 230 patients were tested for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti‐HBc) before treatment. Fifty‐six (24.3%) of 230 patients were anti‐HBc positive, and the remaining 174 (75.6%) patients were anti‐HBc negative. Among the 56 anti‐HBc–positive patients, 5 (8.9%) became HBsAg positive (HBV reactivation), whereas none of the 174 anti‐HBc–negative patients became HBsAg positive with a median follow‐up of 24 months (P = .001). Among the 5 patients with HBV reactivation, 4 were negative for antibody to HBsAg (anti‐HBs), and 1 patient was positive for anti‐HBs. All 5 of these patients were treated successfully with entecavir on detection of HBsAg, although 4 of the 5 patients exhibited mild to moderate elevation of alanine aminotransferase. Among 56 anti‐HBc–positive patients, those negative for anti‐HBs had a higher probability of developing HBV reactivation compared with those positive for anti‐HBs (4 of 19; 21.1% vs 1 of 37; 2.7%, P = .014). CONCLUSIONS: Patients with isolated anti‐HBc are at high risk of HBV reactivation and should be monitored closely for HBsAg, anti‐HBs, HBV‐DNA, and transaminase levels during and after rituximab‐containing treatment. Although preemptive use of entecavir enabled successful management of HBV reactivation, mild to moderate hepatic flare was still observed. These approaches should be further evaluated in a prospective study with regard to clinical usefulness, safety, and cost‐effectiveness. Cancer 2010. © 2010 American Cancer Society. This paper describes the incidence and risk factors for HBV reactivation after the use of rituximab in hepatitis B surface antigen‐negative patients with CD20‐positive B‐cell lymphomas. The authors found that patients positive for antibody to hepatitis B core antigen, especially those who were negative for antibody to hepatitis B surface antigen, were at high risk for developing HBV reactivation after treatment with rituximab‐containing therapy.