title: Hepatitis B surface antigen seroclearance during nucleoside analogue therapy: surface antigen kinetics, outcomes, and durability.
abstract: BACKGROUND
  Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described.
  
  
  METHODS
  We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined.
  
  
  RESULTS
  The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year; p = 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year; p = 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (p < 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3% (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant.
  
  
  CONCLUSIONS
  NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong. wkseto@hku.hk.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong. wkseto@hku.hk.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, 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, Pokfulam Road, Pokfulam, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: Fung-Yu
authors.initials: FY
authors.lastname: Huang
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: Kevin Sze-Hang
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Pokfulam, 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, Pokfulam Road, Pokfulam, Hong Kong.|State Key Laboratory for Liver Research, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong.
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D009705:Nucleosides
keywords: Antibody to hepatitis B surface antigen; Antiviral; Covalently closed circular DNA; Hepatitis B surface antigen; Hepatitis B virus