Serum levels of interferon-gamma-inducible protein 10 and response to peginterferon therapy in HBeAg-positive chronic hepatitis B

J Hepatol. 2013 May;58(5):898-903. doi: 10.1016/j.jhep.2013.01.029. Epub 2013 Jan 29.

Abstract

Background & aims: Serum levels of interferon-gamma inducible protein 10 (IP-10) are a marker for immune activity, and may predict response to peginterferon (PegIFN) therapy in chronic hepatitis B.

Methods: IP-10 was measured at baseline and on-treatment week 12 in 210 HBeAg-positive patients treated with PegIFN for 52 weeks. Response to treatment was assessed at 6 months post-treatment and defined as HBeAg loss, combined response (HBeAg loss with HBV DNA <10,000 c/ml) or HBsAg loss.

Results: Median baseline IP-10 levels were 158 pg/ml. Higher baseline IP-10 was associated with more HBV DNA, HBeAg and HBsAg decline from week 4 onwards, and IP-10 was higher in patients who achieved HBeAg loss (p=0.001) and combined response (p=0.052). A combination of high IP-10 (>150 pg/ml) with absence of precore (PC) and core promoter (BCP) mutants strongly predicted combined response and HBsAg loss: 48% of patients with high IP-10 and no detectable mutants achieved a combined response (p<0.001). A minimal non-significant decline from baseline was observed to week 12 (0.015 log pg/ml, p=0.52 compared to baseline), but decline was somewhat more pronounced in patients who achieved HBeAg loss (0.05 logpg/ml, versus an increase of 0.05 in patients without HBeAg loss, p=0.04).

Conclusions: Higher pre-treatment IP-10 levels are associated with an increased probability of HBeAg loss after PegIFN therapy. A combination of high baseline IP-10 and absence of PC and BCP mutants identified patients with the highest probability of combined response and HBsAg loss. There appears little use for on-treatment quantification of IP-10 for prediction of response to PegIFN.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Chemokine CXCL10 / blood*
  • DNA, Viral / blood
  • Female
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Polyethylene Glycols / therapeutic use*
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Viral Core Proteins / genetics

Substances

  • Antiviral Agents
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Viral Core Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2b