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69
Longitudinal serologic profiles up to 5 years in hepatitis B surface antigen-negative chronic hepatitis B
Wai-Kay Seto1, Yasuhito Tanaka2, Danny Wong1, Noboru
Shinkai2, Ka-Shing Cheung1, Sze Hang Kevin Liu1, James Fung1,
Ching-Lung Lai1, Man-Fung Yuen1; 1Medicine, The University of
Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong;
2Virology and Liver Unit, Nagoya City University Graduate School
of Medical Sciences, Nagoya, Japan
Background: Hepatitis B virus (HBV) persists at low replicative levels among chronic hepatitis B (CHB) patients after hepatitis B surface antigen (HBsAg) seroclearance. The long-term serologic profiles after HBsAg seroclearance in CHB have not been well investigated.
Methods: We used a highly-sensitive HBsAg (hs-HBsAg) assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, Sysmex, Kobe, Japan) for the detection of HBsAg. The lower limit of detection was 0.0005 IU/mL, 100 times more sensitive than conventional HBsAg assays. We measured hs-HBsAg, HBV DNA levels (Cobas Taqman, Roche Diagnostics, lower limit of detection 20 IU/mL) and antibody to HBsAg (anti-HBs,
Abbott Laboratories, lower limit of detection 10 mIU/mL) in CHB patients achieving HBsAg seroclearance, as documented by Elecsys HBsAg II (Roche Diagnostics, lower limit of detection 0.05 IU/mL) at 3 time points: at the time of HBsAg seroclearance, 6-12 months after HBsAg seroclearance and 3-5 years
after HBsAg seroclearance, if available.
Results: 109 patients (76.1% male, genotype B/C distribution 53.2%/47.8%) were
recruited. The mean age of HBsAg seroclearance was 49.5 (±10.9) years, with mean duration of documented HBsAg-positivity at our center before seroclearance 7.5 (±4.2) years. 25 patients (22.9%) were on nucleoside analogue therapy for a mean duration of 5.5 (±3.2) years before HBsAg seroclearance.
11 patients (10.1%) had detectable HBV DNA (median level 37 IU/mL) at HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 19 (20.2%) patients at HBsAg seroclearance, 6-12 months after HBsAg seroclearance and 3-5 years after HBsAg seroclearance respectively
(median detectable levels 0.0409, 0.0173 and 0.0102 IU/mL respectively). Among patients with 3-5 years of follow-up (n=94), hs-HBsAg positive patients at years 3-5, when compared to hs-HBsAg negative patients, had a higher proportion
of anti-HBs negativity (90.0% and 36.5% respectively, p=0.028). When considering all measurements together, anti-HBs negativity, compared to anti-HBs positivity, was associated with a higher rate of hs-HBsAg positivity (66.4% and 24.2% respectively, p<0.001). HBV genotype (B versus C) and presence
of antiviral therapy had no association with hs-HBsAg positivity (p=0.803 and 0.283 respectively).
Conclusion: Serum hs-HBsAg achieved substantial rates of detectability during
HBsAg-negative phase of CHB. Anti-HBs negativity was associated with higher rates of hs-HBsAg detection. Serum hs-HBsAg could potentially assist the differentiation of occult hepatitis B patients from individuals with only past HBV exposure.
Disclosures:
Wai-Kay Seto - Advisory Committees or Review Panels: Gilead Science; Speaking and Teaching: Gilead Science, Bristol-Myers Squibb
Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD.,
MSD, Mitsubishi Tanabe Pharma Corporation, Dainippon Sumitomo Pharma
Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Bristol-Myers Squibb
Ching-Lung Lai - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Gilead Sciences Inc; Consulting: Bristol-Myers Squibb, Gilead Sciences, Inc;
Speaking and Teaching: Bristol-Myers Squibb, Gilead Sciences, Inc
Man-Fung Yuen - Advisory Committees or Review Panels: GlaxoSmithKline,
Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer,
GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers
Squibb, Pfizer; Grant/Research Support: Roche, Bristol-Myers Squibb,
GlaxoSmithKline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmith-
Kline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead
Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Science
The following people have nothing to disclose: Danny Wong, Noboru Shinkai,
Ka-Shing Cheung, Sze Hang Kevin Liu, James Fung
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发表于 2014-10-3 18:38
