title: Longitudinal profiles of highly sensitive hepatitis B surface antigen levels: re-evaluation of HBsAg seroclearance.
abstract: Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well-studied.
  
  
  
  We employed a highly sensitive HBsAg (hs-HBsAg) assay (lower detection limit 0.5 mIU/ml), 100 times more sensitive than conventional HBsAg measurements. CHB patients achieving HBsAg seroclearance defined by conventional assays were followed up for serum hs-HBsAg, HBV DNA and antibody to HBsAg (anti-HBs) levels at 0 months, 6-12 months and 3-5 years after HBsAg seroclearance. Factors associated with hs-HBsAg detectability were determined.
  
  
  
  One hundred and nine patients were recruited; 94 (86.2%) were followed up to years 3-5; and 25 patients (22.9%) were on nucleoside analogue therapy for a median duration of 6.0 (range 1.5-12.7) years before HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 20 (21.3%) patients at 0 months, 6-12 months and 3-5 years respectively. At years 3-5, genotype B patients, when compared to genotype C patients, had a higher anti-HBs positive rate (63.2% and 41.1% respectively, P = 0.036). Serum anti-HBs positivity, when compared to persistent anti-HBs negativity, was associated with a lower rate of hs-HBsAg detection (7.4% and 40% respectively, P < 0.001). Multivariate analysis showed anti-HBs negativity at years 3-5 to be independently associated with persistently positive hs-HBsAg (P = 0.007, odds ratio 7.1, 95% confidence interval 1.7-29.3).
  
  
  
  Serum hs-HBsAg could detect HBsAg presence in a substantial proportion of CHB after HBsAg seroclearance defined by conventional assays, especially among anti-HBs negative individuals. Serum hs-HBsAg could potentially assist differentiating HBsAg-negative CHB from individuals with only past HBV exposure without carrier state.
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Danny K-H
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Shinkai
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Ka-Shing
authors.initials: KS
authors.lastname: Cheung
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Kevin S-H
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, 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; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy; D006723:Hong Kong; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens
keywords: HBV; HBsAg; anti-HBc; anti-HBs; hs-HBsAg