BMC Gastroenterology (Dec 2017)

Time-varying serum gradient of hepatitis B surface antigen predicts risk of relapses after off-NA therapy

  • Nai-Hsuan Chien,
  • Yen-Tsung Huang,
  • Chun-Ying Wu,
  • Chi-Yang Chang,
  • Ming-Shiang Wu,
  • Jia-Horng Kao,
  • Lein-Ray Mo,
  • Chi-Ming Tai,
  • Chih-Wen Lin,
  • Tzeng-Huey Yang,
  • Jaw-Town Lin,
  • Yao-Chun Hsu

DOI
https://doi.org/10.1186/s12876-017-0697-3
Journal volume & issue
Vol. 17, no. 1
pp. 1 – 7

Abstract

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Abstract Background The serum gradient of hepatitis B surface antigen (HBsAg) varies over time after cessation of nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB). The association between the time-varying HBsAg serum gradient and risk of relapse has not been elucidated. Methods This multicenter cohort study prospectively enrolled CHB patients who discontinued 3 year-NA treatment. Eligible patients were serologically negative for HBeAg and viral DNA at NA cessation. The participants (n = 140) were followed every 3 months through HBsAg quantification. Virological and clinical relapses were defined as viral DNA levels >2000 IU/mL and alanine aminotransferase (ALT) levels >80 U/mL, respectively. The association of time-varying HBsAg levels with relapses was assessed through a time-dependent Cox analysis. Results During a median follow-up of 19.9 (interquartile range [IQR], 10.6–25.3) months, virological and clinical relapses occurred in 94 and 49 patients, with a 2-year cumulative incidence of 79.2% (95% confidence interval [CI], 70.9%–86.4%) and 42.9% (95% CI, 34.1%–52.8%), respectively. The serum level of HBsAg was associated with virological (P < 0.001) and clinical (P = 0.01) relapses in a dose–response manner, with adjusted hazard ratios of 2.10 (95% CI, 1.45–3.04) and 2.32 (95% CI, 1.28–4.21). Among the patients (n = 19) whose HBsAg levels ever dropped below 10 IU/mL, only one and three patients subsequently developed clinical and virological relapses. Conclusion The serum gradient of HBsAg measured throughout the off-therapy observation is associated with the subsequent occurrence of virological and clinical relapses in CHB patients who discontinue NA treatment.

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