IP-10 Expression in Patients with Chronic HBV Infection and Its Ability to Predict the Decrease in HBsAg Levels after Treatment with Entecavir

Mol Cells. 2017 Jun 30;40(6):418-425. doi: 10.14348/molcells.2017.0051. Epub 2017 Jun 14.

Abstract

Interferon-γ-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy.

Keywords: IP-10; chronic hepatitis B; entecavir; prediction.

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Biopsy
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / metabolism*
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Hep G2 Cells
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / pathology*
  • Humans
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Serologic Tests

Substances

  • Antiviral Agents
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Hepatitis B Surface Antigens
  • entecavir
  • Guanine
  • Aspartate Aminotransferases
  • Alanine Transaminase