Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative patients receiving nucleos(t)ide analogues

PLoS One. 2017 Nov 30;12(11):e0188303. doi: 10.1371/journal.pone.0188303. eCollection 2017.


Background: HBeAg-negative chronic hepatitis B patients require long-term nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual. Low quantitative HBsAg (qHBsAg) levels can identify patients with higher probability of seroclearance. The aim of our study was to evaluate qHBsAg in HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and seroclearance.

Methods: Retrospective analysis of qHBsAg in HBeAg-negative patients before and at years 1, 3, 5, 8 and over of NAs treatment.

Results: From 1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up in 14% of patients and HBsAg loss in 4%. No baseline variables predicted seroclearance and only treatment duration predicted low qHBsAg. The annual decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04 years. The decline was greater in patients achieving low HBsAg levels (-0.257) than in those who did not (-0.057)(p<0.001). The diagnostic accuracy (ROC curve, 95%CI) of qHBsAg delta at year 3 was 0.89 (0.81-0.97), with cut-off >0.3 log IU/mL showing a positive and negative predictive value of 42% and 100% to identify patients achieving low levels of HBsAg.

Conclusions: Reduction of qHBsAg is slow in HBeAg-negative patients receiving NAs, although low levels or faster qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can identify patients with a higher probability of achieving low levels and HBsAg seroclearance.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Female
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens

Grants and funding

JAC has received a grant from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (PI14/00540), co-funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.