目的探讨慢性乙肝病毒（hepatitis B virus，HBV）感染者外周血Th17/Treg细胞因子［白细胞介素（IL）-6、IL-17、IL-10和转化生长因子-β（TGF-β）］及高尔基体糖蛋白-73（Golgi protein-73，GP73）、血管内皮生长因子（vascular endothelial growth factor，VEGF）的表达水平的差异及临床意义，同时分析肝癌患者细胞因子与GP73和VEGF的相关性。
方法前瞻性收集2017年9月至2020年5月烟台市奇山（传染病）医院收治的114例HBV感染者作为研究对象，其中男性76例，女性38例，年龄（43.38±12.72）岁。将其分为慢性乙型肝炎（CHB）组51例、肝硬化（LC）组31例、肝癌（HCC）组32例。以同期健康体检者40例作为对照组，男性25例，女性15例，年龄（39.15±14.95）岁。运用酶联免疫吸附测定（ELISA）检测4组血清中细胞因子和GP73、VEGF表达水平。组间方差不齐采用Welch方差分析，两两比较采用Games-Howell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验，计数资料组间比较采用 χ 2检验，相关性分析采用Spearman检验。
结果与对照组相比，慢性HBV感染者丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、HBV DNA水平显著升高，差异均有统计学意义（ P＜0.05）；HBV感染者血清IL-6、IL-17、IL-10、TGF-β和VEGF、GP73表达水平均显著升高，差异均有统计学意义（均 P＜0.05）。HCC患者外周血IL-17和IL-10表达水平与VEGF水平呈正相关（ r=0.247、0.286，均 P＜0.05）。
结论Th17/Treg细胞因子、VEGF、GP73可能与HCC的发生发展密切相关，动态监测上述血清指标水平，为临床评估慢性HBV感染状态、判断预后提供循证指导。
ObjectiveTo investigate the value and clinical significance of the expressions of Th17/Treg associated cytokines [interleukin (IL)-6, IL-17, IL-10, and transforming growth factor-β (TGF-β)], Golgi protein 73 (GP73), and vascular endothelial growth factor (VEGF) in peripheral blood in patients with hepatitis B virus (HBV) infection, and to analyze the correlation of cytokines with GP73 and VEGF in patients with hepatocellular carcinoma (HCC).
MethodsOne hundred and fourteen patients with HBV infection treated at Qishan (Infectious Disease) Hospital from September 2017 to May 2020 were selected as the study objects, including 76 males and 38 females. They were (43.38±12.72) years old. The patients were divided into a chronic hepatitis B (CHB) group (51 cases), a liver cirrhosis (LC) group (31 cases), and a hepatocellular carcinoma (HCC) group. Forty healthy examinees from the same period were selected as a control group, including 25 males and 15 females, and they were (39.15±14.95) years old. The cytokine, VEGF, and GP73 levels were measured by enzyme linked immunosorbent assay (ELISA). A Welch analysis of variance was used for the comparison of normally distributed continuous data with heterogeneity of variance between the groups. The Games-Howell test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between the groups.The chi square test was used for the comparison of categorical data between the groups. The Spearman correlation analysis was used to investigate the correlation.
ResultsThe levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and HBV DNA in the patients with HBV infection were significantly higher than those in the control group (all P＜0.05). The serum levels of IL-6, IL-17, IL-10, TGF-β, GP73, and VEGF in the patients with HBV infection were significantly higher than those in the control group (all P＜0.05). VEGF was positively correlated with IL-17 and IL-10 in the HCC group ( r=0.247 and 0.286; both P＜0.05).
ConclusionsTh17/Treg associated cytokines, VEGF, and GP73 may play important roles in the pathogenesis of hepatocellular carcinoma. Dynamic monitoring of these serum indicators can provide evidence-based guidance for the clinical assessment of chronic HBV infection status and prognostic judgment.
Yang Yongwei and Chen Xilian are the first authors.
杨勇卫,陈锡莲,曲人亮,等. 慢性HBV感染者Th17/Treg细胞因子、VEGF、GP73表达水平差异与临床意义研究[J]. 国际医药卫生导报,2021,27(23)：3639-3643.
DOI:10.3760/cma.j.issn.1007-1245.2021.23.010版权归中华医学会所有。
未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。
除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。
杨勇卫和陈锡莲为并列第一作者
杨勇卫, 陈锡莲, 曲人亮, 等. 慢性HBV感染者Th17/Treg细胞因子、VEGF、GP73表达水平差异与临床意义研究[J]. 国际医药卫生导报, 2021, 27(23): 3639-3643. DOI: 10.3760/cma.j.issn.1007-1245.2021.23.010.
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