title: Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study.
abstract: Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis.
  
  
  CONCLUSIONS
  HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Wai-Kay
authors.identifier: http://orcid.org/0000-0002-9012-313X
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Thomas Sau-Yan
authors.initials: TS
authors.lastname: Chan
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Hwang
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Kevin Sze-Hang
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Harinder
authors.initials: H
authors.lastname: Gill
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Yuk-Fai
authors.initials: YF
authors.lastname: Lam
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong.
authors.forename: Eric H Y
authors.initials: EHY
authors.lastname: Lau
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Ka-Shing
authors.initials: KS
authors.lastname: Cheung
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Albert K W
authors.initials: AKW
authors.lastname: Lie
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D011446:Prospective Studies; D012008:Recurrence; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; C413685:entecavir; D006147:Guanine