title: Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab.
abstract: OBJECTIVE
  Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab.
  
  
  METHODS
  Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy.
  
  
  RESULTS
  Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation.
  
  
  CONCLUSIONS
  Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.
authors.affiliation: Department of Clinical Oncology, Stanley Ho Centre for Emerging Infectious Diseases, School of Public Health, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. winnieyeo@cuhk.edu.hk
authors.forename: Winnie
authors.initials: W
authors.lastname: Yeo
authors.forename: Tung C
authors.initials: TC
authors.lastname: Chan
authors.forename: Nancy W Y
authors.initials: NW
authors.lastname: Leung
authors.forename: Wai Y
authors.initials: WY
authors.lastname: Lam
authors.forename: Frankie K F
authors.initials: FK
authors.lastname: Mo
authors.forename: Miu Ting
authors.initials: MT
authors.lastname: Chu
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Hui
authors.forename: Kenny I K
authors.initials: KI
authors.lastname: Lei
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D014775:Virus Activation
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D006514:Hepatitis B Surface Antigens; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone