title: Hepatic flares promote rapid decline of serum hepatitis B surface antigen (HBsAg) in patients with HBsAg seroclearance: A long-term follow-up study.
abstract: OBJECTIVE
  Serum hepatitis B surface antigen (HBsAg) seroclearance is one of the ultimate goals of management of chronic hepatitis B. We investigated the kinetics of serum HBsAg before HBsAg seroclearance in patients with chronic hepatitis B.
  
  
  METHODS
  We retrospectively analyzed 392 Japanese chronic hepatitis B patients who had been followed for 5 years or more between 1980 and 2000. Serum HBsAg levels were measured annually using chemiluminescent enzyme immunoassay.
  
  
  RESULTS
  During a median follow up of 14 years, 50 patients demonstrated HBsAg seroclearance (annual incidence rate, 0.91%). Multivariate analysis with baseline characteristics revealed that HBsAg of less than 3.3 log IU/mL (hazard ratio [HR], 2.22; P = 0.008) and treatment with nucleoside/nucleotide analog (HR, 0.12; P = 0.001) were independent predictive factors for seroclearance. The median HBsAg levels at 20, 10, 5, 3 and 1 year prior to seroclearance were 3.89, 2.84, 1.84, 0.78 and -1.10 log IU/mL, respectively. The rapid decline group, comprising patients who achieved HBsAg seroclearance within 5 years after confirmed HBsAg levels of 2 log IU/mL, demonstrated: (i) high alanine aminotransferase (ALT) levels; and (ii) a low frequency of liver cirrhosis progression. A significant reduction in annual HBsAg levels was found in years marked by at least one ALT flare (ALT ≥200 IU/L) (flare [+], n = 62) than in those without (flare [-], n = 323) (0.29 vs 0.17 log IU/mL/year, P = 0.003).
  
  
  CONCLUSIONS
  Hepatic flares promoted rapid declines and greater annual reductions of HBsAg levels in patients with HBsAg seroclearance.
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Abiru
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shigemune
authors.initials: S
authors.lastname: Bekki
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Saeki
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ezaki
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
keywords: alanine aminotransferase flare; chronic hepatitis B; hepatitis B surface antigen quantification; hepatitis B surface antigen seroclearance