乙型肝炎病毒感染患者PBMC表面PD-1、Caspase-9在不同病情阶段中临床表达意义

Clinical expression significance of PD-1 and Caspase-9 on the surface of PBMC in patients with hepatitis B virus infection at different stages of the disease

目的探究乙型肝炎患者不同阶段的外周血单个核细胞(PBMC)表面程序性死亡受体-1(PD-1)、半胱氨酸天冬氨酸酶-9(Caspase-9)水平,寻找其临床表达意义。方法选取湘潭市中心医院感染性疾病与肝病科2020年3月至2022年9月进行治疗的224例乙型肝炎患者,根据其病情阶段将所有患者分成乙型肝炎轻度组(n=83)、乙型肝炎中度组(n=76)和乙型肝炎重度组(n=65)。另取同期肝癌患者21例作为肝癌组,同期健康体检人员70例归入健康组。比较各组乙型肝炎患者肝功能指标,PBMC表面PD-1、Caspase-9水平,统计分析不同病情阶段与PBMC表面PD-1、Caspase-9水平的关系以及其对于病情阶段的预测价值。结果乙型肝炎轻度组、乙型肝炎中度组、乙型肝炎重度组患者以及肝癌患者的谷草转氨酶(AST)、谷丙转氨酶(ALT)、乙型肝炎DNA(HBV-DNA)都显著高于健康组,乙型肝炎轻度组、乙型肝炎中度组、乙型肝炎重度组和肝癌组AST、ALT依次升高,并且各组之间差异有统计学意义(P<0.05)。乙型肝炎轻度组、乙型肝炎中度组、乙型肝炎重度组患者以及肝癌组患者PBMC表面PD-1、Caspase-9水平明显高于健康组(P<0.05)。乙型肝炎轻度组、乙型肝炎中度组、乙型肝炎重度组和肝癌组Caspase-9水平依次降低,各组之间差异有统计学意义(P<0.05)。乙型肝炎轻度组、乙型肝炎重度组和肝癌组PBMC表面PD-1依次升高,各组差异有统计学意义(P<0.05);中度组PD-1和轻度组差异无统计学意义(P>0.05)。PBMC表面PD-1与AST、ALT呈正相关,与HBV-DNA呈负相关,而Caspase-9水平与AST、ALT呈负相关,与HBV-DNA呈正相关,PBMC表面PD-1、Caspase-9水平联合检测重度乙型肝炎发展为肝癌的AUC值为0.911,敏感度为90.31%,特异度为89.63%。结论乙型肝炎患者不同阶段的PBMC表面PD-1、Caspase-9水平有显著差异,且两者表达水平与肝功能指标存在相关性,进行PD-1、Caspase-9的联合检测可以对重度乙型肝炎发展为肝癌进行预测。

Objective To investigate the levels of programmed death receptor-1(PD-1)and cysteinyl aspartate specific proteinase-9(Caspase-9)on the surface of peripheral blood mononuclear cells(PBMC)in different stages of patients with hepatitis B,and to find their clinical expression significance.Methods A total of 224 patients with hepatitis B who were treated in the Department of Infectious Diseases and Hepatology of Xiangtan Central Hospital from March 2020 to September 2022 were selected.All patients were divided into the mild hepatitis B group(n=83),moderate hepatitis B group(n=76),and severe hepatitis B group(n=65)according to their disease stages.21 patients with liver cancer during the same period were selected as the liver cancer group,and 70 health examination personnel during the same period were included in the health group.The liver function indicators,the levels of PD-1 and Caspase-9 on the surface of PBMC in each group of patients with hepatitis B were compared,and the relationship between different stages of the disease and the levels of PD-1 and Caspase-9 on the surface of PBMC was statistically analyzed,as well as its predictive value for the disease stage.Results The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and hepatitis B virus-DNA(HBV-DNA)in patients of the mild hepatitis B group,moderate hepatitis B group and severe hepatitis B group,and liver cancer patients were significantly higher than those in the healthy group.AST and ALT in the mild hepatitis B group,moderate hepatitis B group,severe hepatitis B group,and liver cancer group increased in turn,with statistically significant differences between the groups(P<0.05).The levels of PD-1 and Caspase-9 on the PBMC surface in the mild hepatitis B group,moderate hepatitis B group,severe hepatitis B group,and liver cancer group were significantly higher than those in the healthy group(P<0.05).The levels of Caspase-9 in the mild hepatitis B group,moderate hepatitis B group,severe hepatitis B group,and liver cancer group decreased in turn,with statistically significant differences between the groups(P<0.05).The PD-1 on the surface of PBMC in the mild hepatitis B group,severe hepatitis B group,and liver cancer group increased in turn,with statistically significant differences between the groups(P<0.05).There was no difference in PD-1 between the moderate group and the mild group(P>0.05).PD-1 on the surface of PBMC was positively correlated with AST and ALT,and negatively correlated with HBV-DNA,while Caspase-9 was negatively correlated with AST and ALT,and positively correlated with HBV-DNA.The AUC value of the combined detection of PD-1 and Caspase-9 for the development of severe hepatitis B into liver cancer was 0.911,the sensitivity was 90.31%,and the specificity was 89.63%.Conclusion The levels of PD-1 and Caspase-9 on PBMC surface in different stages of hepatitis B patients are significantly different,and the expression levels of PD-1 and Caspase-9 are correlated with liver function indicators.The combined detection of PD-1 and Caspase-9 can predict the development of severe hepatitis B into liver cancer.