Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study

Abstract

PurposePatterns 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 MethodsHBsAg-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.ResultsAmong 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.ConclusionA 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.