Association of KIR Genotypes and Haplotypes in HBeAg-positive Chronic Hepatitis B Patients Treated with Entecavir

Background:A large proportion of patients with chronic hepatitis B (CHB) in China do not respond to entecavir (ETV) treatment. It remains unclear whether the Killer immunoglobulin-like receptor (KIR) genotypes and haplotypes were associated with the advantage of seroconversion in phepatitis B e-Antigen (HBeAg) positive CHB patients treated with ETV. Methods: Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to analyze KIR genes in a Chinese Han population of 198 ETV-treated HBeAg-positive CHB patients and 200 healthy controls. Of the 198 patients, 59 were complete response group (CRG) and 139 were null or partial response group (NPRG) to the treatment with ETV. Results: The frequencies of KIR genotype M, and haplotype 8 were significantly higher(P = 0.017, OR = 2.497，95%CI = 5.39–1.16 and P = 0.034, OR = 1.905，95%CI = 3.48–1.04, respectively), while the frequencies of genotype AH and haplotype 5 were significantly lower (P = 0.039, OR = 0.504, 95%CI = 0.97–0.26 and P = 0.031, OR = 0.601, 95%CI = 0.96–0.38, respectively) in HBeAg-positive CHB patient group than those in healthy group. Of note, the frequencies of KIR genotype AF and haplotype 1 were significantly higher (P = 0.022, OR = 2.860, 95%CI = 7.24–1.13 and P = 0.001, OR = 3.261, 95%CI = 6.47–1.64, respectively), while the frequencies of genotype AH and haplotype 5 were significantly lower (P = 0.038, OR = 0.338, 95%CI = 0.98–0.12 and P = 0.004, OR = 0.354, 95%CI = 0.73–0.17, respectively) in NPRG than those in CRG. Conclusions: The patients with KIR genotype AF and haplotype 1 might be negative, while genotype AH and haplotype 5 might be of advantage to the therapy with ETV, which are useful for improving novel personalized precise therapy strategy in HBeAg-positive CHB patients.