The association between serum cytokine and chemokine levels and antiviral response by entecavir treatment in chronic hepatitis B patients

Antivir Ther. 2018;23(3):239-248. doi: 10.3851/IMP3196.

Abstract

Background: Although nucleoside/nucleotide analogue therapy is thought to suppress chronic hepatitis B (CHB) via regulation of inflammatory cytokines/chemokines, the mechanism is still unclear. In this study, serum cytokine/chemokine levels were measured in CHB patients treated with entecavir, and the association with antiviral response was analysed.

Methods: A total of 78 Japanese patients with CHB were enrolled, and serum cytokine/chemokine levels were measured at baseline and at 12, 24 and 48 weeks of entecavir treatment using the MULTIPLEX kit.

Results: Antiviral response to entecavir treatment was significantly associated with hepatitis B surface antigen (HBsAg) titre and serum interferon-gamma-inducible protein 10 (IP-10) level (12w; P=0.0002; OR=0.020 [95% CI 0.002, 0.156], P=0.003; OR=0.042 [95% CI 0.005, 0.336], respectively). HBe-positive patients whose serum macrophage-derived chemokine (MDC) level was lower (<582.83 pg/ml) and IP-10 level was higher (≥1,323.13 pg/ml) achieved hepatitis B e antigen (HBeAg) loss earlier than those who remained HBeAg-positive (P=0.044). HBsAg reduction by entecavir treatment was significantly associated with higher initial tumour necrosis factor-alpha (TNF-α) level (≥15.20 pg/ml) and higher alanine aminotransferase level (≥73 IU/l; P=0.009; OR=18.460 [95% CI 2.044, 166.709], P=0.022; OR=7.709 [95% CI 1.341, 44.327], respectively).

Conclusions: Results of the present study indicate that changes in cytokine/chemokine levels following entecavir therapy are associated with response to antiviral therapy in CHB patients. Monitoring of serum cytokine/chemokine levels could be useful for predicting reduction of HBV DNA and HBsAg and HBe seroconversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Biomarkers
  • Chemokines / blood*
  • Cytokines / blood*
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • Chemokines
  • Cytokines
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • entecavir
  • Guanine