乙型肝炎相关性肝功能衰竭患者外周血PD-1表达的临床意义

Clinical significance of PD-1 expression in peripheral blood in patients with HBV related liver failure

目的观察乙型肝炎相关性肝功能衰竭患者细胞程序性死亡因子-1(PD-1)表达特点及临床意义。方法针对不同表位合成3种pentamer,采集16例急性和慢加急性肝功能衰竭患者外周血,并收集15例急性乙型肝炎(AHB)患者外周血作为对照,流式细胞仪分析各组病毒特异性CTL细胞的频率及其表面PD-1分子表达水平,同时观察与肝功能和血清HBV DNA载量的相关性。组间比较采用Mann-whitney U检验。结果与AHB患者比较,肝功能衰竭患者发病早期病毒特异性CD8 T淋巴细胞PD-1表达水平显著降低,该阶段PD-1表达水平与转氨酶呈显著正相关,但与病毒载量无明显相关性。随访发现,AHB患者早期,PD-1高水平表达,随着疾病康复,PD-1表达逐渐降低;而肝功能衰竭患者早期PD-1表达较低,随后显著增加,而后随着疾病恢复,PD-1进一步降低。结论肝功能衰竭患者发病早期外周血PD-1表达水平较AHB患者显著降低,而PD-1延迟高表达则与急性肝功能衰竭的发生密切相关。

Objective Programmed death-1 （PD-1） up-regulation can impair virus-specific CD8 T-cell responses during chronic viral infection. The correlation between PD-1 expression and liver failure in HBV infection, however, remain largely undefined. This study aimed at characterizing the PD-1 expression during liver failure, and further addressing how PD-1 regulates liver injury in HBV infection. Methods HBV-specific CD8 T cells in peripheral blood from 16 patients with liver failure and 15 AHB patients were quantitatively analyzed and PD-1 expression in HBV-specific CI38 T cells were measured by using flow cytometry. The correlation between PD-1 expression and function liver and serum HBV DNA load was performed for analyses of the impact of PD-1 expression. Results Compared with acute HBV infection PD-1 expression in HBV-specific CD8 T cells was significantly down-regulated in the early phase of liver failure. PD-1 expression was further found to be positively correlated with ALT levels but not HBV load in the early phase of liver failure. During the follow-up period, compared with AHB patients who displayed a gradual decline of PD-1 with the recovery of disease, PD-1 up-regulation was found to be delayed. Conclusion Compared with acute HBV infection, PD-1 expression in HBV-specific CD8 T cells was significantly down-regulated in the early phase of liver failure while the delayed PD-1 up-regulation was closely correlated with the occurrence of liver failure. PD-1/PD-L1 pathway, therefore, may play a key role in the pathogenesis of liver failure.