title: Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, Kamogawa-shi, Chiba, Japan. kmatsue@kameda.jp
authors.forename: Kosei
authors.initials: K
authors.lastname: Matsue
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Kimura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takanashi
authors.forename: Kan-ichi
authors.initials: K
authors.lastname: Iwama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamakura
authors.forename: Masami
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006510:Hepatitis B Antibodies / Q000032:analysis; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D014775:Virus Activation
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D000069283:Rituximab