title: Prospective long-term study of hepatitis B virus reactivation in patients with hematologic malignancy.
abstract: OBJECTIVE
  To elucidate the clinical characteristics of hepatitis B virus reactivation (HBV-R), we performed a prospective long-term study of patients with hematologic malignancy, including both hepatitis B virus (HBV) carriers and those with resolved HBV infection.
  
  
  METHODS
  Twenty-one patients with hematopoietic stem-cell transplants (HSCT) and 36 patients given rituximab-based chemotherapy were enrolled. Entecavir was administered prophylactically to eight patients with HBV surface antigen (HBsAg). HBV-DNA was measured every month in 49 patients with resolved HBV infection, and preemptive therapy was given to eight patients with HBV-R.
  
  
  RESULTS
  HBV-R developed in five (26%) of 19 patients with HSCT and three (10%) of 30 patients given rituximab-based chemotherapy. HBV-R occurred a median of 3 months (range: 2-10) after the end of rituximab-based chemotherapy and 22 months (range: 9-36) after HSCT. HBV-R did not develop in patients with an antibodies against HBsAg (anti-HBs) titer exceeding 200 mIU/mL at baseline. Mutations in the "a" determinant region with amino acid replacement were detected in four of the eight patients with HBV-R. Preemptive therapy prevented severe hepatitis related to HBV-R. Entecavir treatment was stopped in four patients with HBV-R. Since the withdrawal of entecavir, HBV-DNA has not been detected in two patients persistently positive for anti-HBs. No patient had fatal hepatitis.
  
  
  CONCLUSIONS
  Proper management of patients with HBsAg or resolved HBV infection prevented fatal hepatitis related to HBV-R in patients who received immunosuppressive or cytotoxic therapy. Entecavir could be safely discontinued in patients with HBV-R who had acquired anti-HBs.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kawamura
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Sawako
authors.initials: S
authors.lastname: Uchida-Kobayashi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Morikawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000998:Antiviral Agents / Q000008:administration & dosage; D002353:Carrier State; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006509:Hepatitis B / Q000517:prevention & control / Q000821:virology*; D006514:Hepatitis B Surface Antigens; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D013997:Time Factors; D014775:Virus Activation; D028761:Withholding Treatment
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; D000069283:Rituximab; C413685:entecavir; D006147:Guanine
keywords: HBV reactivation; HBV-DNA; anti-HBs; prospective study