Trajectories of serum hepatitis B surface antigen kinetics in patients with chronic hepatitis B receiving long-term nucleos(t)ide analogue therapy

Liver Int. 2018 Apr;38(4):627-635. doi: 10.1111/liv.13564. Epub 2017 Sep 15.

Abstract

Background & aims: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) patients remains unclear. We investigated the patterns of serum HBsAg kinetics and their association with therapeutic outcomes in genotype B- or C-infected CHB patients receiving long-term NA therapy.

Methods: We enrolled 329 treatment-naive CHB patients receiving NA therapy for >5 years to analyse the kinetic patterns by using group-based trajectory models (GBTMs).

Results: Most patients (82.4%) received entecavir therapy. The median treatment duration was 83.6 (68.5-89.7) months. The GBTMs revealed three groups for both the hepatitis B e antigen (HBeAg)-positive and -negative patients. The median annual decline in serum HBsAg levels during the first 5 years was significantly higher in Group 1 than in Groups 2 and 3 in HBeAg-positive (0.78 vs 0.10 vs 0.10 log10 IU/mL) and HBeAg-negative (0.71 vs 0.08 vs 0.09 log10 IU/mL) patients. HBsAg levels at the baseline and 12 months combined with an HBsAg decline from the baseline to 12 months of treatment predicted trajectory pattern 1 in HBeAg-positive (sensitivity, 77.8%; specificity, 99.1%; positive predictive value [PPV], 87.5%; and negative predictive value [NPV], 98.2%) and HBeAg-negative (sensitivity, 100%; specificity, 99.5%; PPV, 88.9%; and NPV, 100%) patients. The trajectory patterns were significantly associated with HBeAg loss in the HBeAg-positive patients and the achievement of HBsAg <100 IU/mL or HBsAg loss in HBeAg-positive and HBeAg-negative patients.

Conclusions: The trajectory of serum HBsAg levels predicts HBsAg loss in CHB patients receiving long-term NA therapy.

Keywords: HBsAg loss; chronic hepatitis B; group-based trajectory models; hepatitis B surface antigen; nucleos(t)ide analogue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • DNA, Viral / blood
  • Female
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Sensitivity and Specificity
  • Taiwan

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • entecavir
  • Guanine