Association between KIR Genes and Efficacy of Treatment of HBeAg-Positive Chronic Hepatitis B Patients with Entecavir

Iran J Immunol. 2018 Jun;15(2):112-121.

Abstract

Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China. However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not respond to ETV therapy.

Objective: To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion in HBeAg positive CHB responder patients treated with ETV.

Methods: Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was performed to genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients which 59 were defined as the complete response group (CRG) to the treatment with ETV and 139 were defined as null or partial response group (NPRG).

Results: The frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030, OR=1.57,95%CI=2.36-1.05 and P=0.018, OR=1.773,95%CI=2.77-1.13, respectively), while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower (P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and P=0.035, OR=0.641, 95%CI=0.96-0.43, respectively) in HBeAg-positive CHB patients than those in healthy controls. The frequency of KIR2DS3 gene was significantly higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949, 95%CI=3.65-1.04, respectively).

Conclusion: Patients with KIR2DS3 might have negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and KIR3DS1 might have advantage in the therapy with ETV.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Biomarkers
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B e Antigens / blood
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenomic Variants*
  • Receptors, KIR / genetics*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Biomarkers
  • Hepatitis B e Antigens
  • Receptors, KIR
  • entecavir
  • Guanine