title: Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study.
abstract: OBJECTIVE
  Patterns 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.
  
  
  METHODS
  HBsAg-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.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Thomas S Y
authors.initials: TS
authors.lastname: Chan
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Hwang
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Kevin Sze-Hang
authors.initials: KS
authors.lastname: Liu
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Harinder
authors.initials: H
authors.lastname: Gill
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Yuk-Fai
authors.initials: YF
authors.lastname: Lam
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Albert K W
authors.initials: AK
authors.lastname: Lie
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: All authors: The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China. mfyuen@hkucc.hku.hk.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D014775:Virus Activation
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D000069283:Rituximab