Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3′-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1–2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1–2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.

已知程序性死亡配体 1 (sPD-L1) 的可溶性分子可调节 T 细胞耗竭，这是乙型肝炎病毒 (HBV) 持续存在和肝病进展的重要机制。此外，3'-UTR 中的 PD-L1 多态性可以影响 PD-L1 的表达，并与癌症风险相关，尽管不是绝对的。本研究的目的是调查PD-L1多态性与 sPD-L1 循环水平在 HBV 感染和疾病进展中的关联。在这项研究中，551 名 HBV 感染患者属于三个临床明确定义的慢性乙型肝炎亚组（CHB，n = 186）、肝硬化（LC，n = 142）和肝细胞癌（HCC，n = 223）和 240 名健康个体 (HC) 参加。PD-L1 多态性 ( rs2297136和rs4143815）通过内部验证的 ARMS 分析进行基因分型。应用逻辑回归模型以确定 PD-L1 多态性与 HBV 感染以及相关肝病进展的关联。血浆 sPD-L1 水平通过 ELISA 测定进行量化。该PD-L1 rs2297136 AA基因型与HBV感染易感性相关（HBV与HC：OR = 1.6; 95％CI = 1.1-2.3; P = 0.0087）和疾病进展（LC与CHB：OR = 1.8; 95％ CI = 1.1–2.9；p = 0.018）。而rs2297136GG基因型是HCC发展的保护因素。HBV 患者的血浆 sPD-L1 水平显着升高（p < 0.0001），LC 组的血浆 sPD-L1 水平更高，其次是 CHB 和 HCC 组。高 sPD-L1 水平与肝酶升高和晚期肝病进展（Child-pugh C > B > A，p < 0.0001）和 BCLC 分类（BCLC D > C > B > A，p = 0.031）相关。我们首次得出结论，PD-L1 rs2297136多态性和血浆 sPD-L1 蛋白水平与 HBV 感染和 HBV 相关肝病进展相关。