摘要：The inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (
PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of
PD-1.5 and
PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of
PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The
PD-1.9 T allele and
PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of
PD-1.5 TT genotype and
PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype
CT (
PD-1.5 C and
PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the
TC (
PD-1.5 T and
PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The
PD-1.5 CC, PD-1.9 TT, genotype, and the
CC (
PD-1.5 C and
PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients.
PD-1.5 and
PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.
