title: Association of Hepatitis B Core-Related Antigen With Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy.
abstract: Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined.
  
  
  
  HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml-1, developed.
  
  
  
  One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively).
  
  
  
  Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 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, 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, 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, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 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, 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, 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, Hong Kong.
authors.forename: Yuk-Fai
authors.initials: YF
authors.lastname: Lam
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 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, Hong Kong.
authors.forename: Albert K W
authors.initials: AK
authors.lastname: Lie
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, 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, 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, Hong Kong.|State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D044466:Asian People; D002353:Carrier State / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006510:Hepatitis B Antibodies / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000097:blood* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000069283:Rituximab / Q000009:adverse effects*; D014184:Transplantation, Homologous; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D000069283:Rituximab