Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy

J Hepatol. 2014 Jan;60(1):62-8. doi: 10.1016/j.jhep.2013.08.023. Epub 2013 Sep 6.


Background & aims: Serum HBsAg levels might represent an important predictor of sustained off-treatment response in HBeAg-negative chronic hepatitis B (CHB). We evaluated the changes of HBsAg and interferon-inducible protein 10 (IP10) serum levels in HBeAg-negative CHB patients treated with entecavir.

Methods: 114 patients received entecavir for a median of 4.3 years. HBsAg levels were determined at baseline, 6 and 12 months and every year thereafter until year-4. IP10 levels were measured at baseline and annually until year-4 in 76 patients.

Results: Virological remission rates were high (year-1: 94%, after year-2: 97-98%). Compared to baseline, HBsAg levels decreased by a median of 0.03, 0.13, 0.17, 0.22, and 0.32 log₁₀ IU/ml at 6 months and 1, 2, 3, and 4 years, respectively (p≤0.001 for all comparisons). The proportions of patients with HBsAg decline of ≥0.5 or ≥1 log₁₀ IU/ml were 9% or 6% at year-1 and 21% or 10% at the last visit. Median IP10 levels (pg/ml) did not change from baseline to year-1 or -2 (245 vs. 229 or 251), but increased at year-3 and -4 (275 and 323, p<0.030). HBsAg drop ≥0.5 log₁₀ was associated with baseline IP10 or IP10 >350 pg/ml (p≤0.002). HBsAg loss occurred in 4/114 (3.5%) patients or in 1/2, 3/21, and 0/91 patients with baseline HBsAg <100, 100-1000 and >1000 IU/ml, respectively (p<0.001).

Conclusions: In HBeAg-negative CHB patients, 4-year entecavir therapy decreases serum HBsAg levels, but the rate of decline is rather slow. Serum IP10 levels represent a promising predictor of HBsAg decline in this setting.

Keywords: ALT; Entecavir; HBV; HBeAg; HBsAg; Hepatitis B; IQR; Interferon-inducible protein 10; LSM; NA(s); PCR; SD; ULN; alanine aminotransferase; anti-HBe; antibody against HBeAg; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; interquartile range; liver stiffness measurement; nucleos(t)ide analogue(s); polymerase chain reaction; standard deviation; upper limit of normal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Chemokine CXCL10 / blood*
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models


  • Antiviral Agents
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • entecavir
  • Guanine