Abstract:

Objective　To investigate the changes and clinical significance of the levels of the T-cell subsets (CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺), fibrin degradation complex (DR-70), and chitinase 3-like protein 1 (CHI3H1) in patients with different clinical classification of hepatitis B virus (HBV) infections, and to analyze the correlation of T lymphocyte subsets with CHI3H1 and DR-70 in patients with HBV related hepatocellular carcinoma. Methods　One hundred and seventy-three patients with chronic HBV infection treated at Qishan Hospital were selected as an experimental group, including 114 males and 59 females who were (45.38±12.72) years old. According to their conditions, there were 59 HBV carriers, 51 cases of chronic hepatitis B, 31 cases of liver cirrhosis, and 32 cases of hepatocellular carcinoma. Forty healthy examinees during the same period were selected as a control group, including 22 males and 18 females who were (39.15±14.95) years old. The various T-cell subsets were measured by flow cytometry. The peripheral blood DR-70 levels were quantitatively detected using the double antibody sandwich enzyme-linked immunosorbent assay. The magnetic particle chemiluminescence method was used to detect the peripheral blood CHI3H1 level. The 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 the comparison between two the groups.The Kruskal-Wallis H test was used for the comparison of the non-normally distributed continuous data between the groups.The χ² test was used for the comparison of the categorical data between the groups. The Pearson correlation analysis was used to investigate the correlation. Results　The CD3⁺ level in the hepatocellular carcinoma group was the lowest [(61.43±19.26)%], and the CD3⁺CD4⁺ level in the liver cirrhosis group was the lowest, with statistical differences from those in the control group (both P<0.05). The levels of DR-70 and CHI3H1 in the chronic hepatitis B group, the liver cirrhosis group, and the hepatocellular carcinoma group increased in different degrees (all P<0.01), and those in the hepatocellular carcinoma group were the highest [(30.11±9.96) mg/L and (213.11±39.76) μg/L; both P<0.01]. The proportion of CD3⁺ T lymphocytes in the peripheral blood in the hepatocellular carcinoma group was negatively correlated with the DR-70 level (r=-0.291, P=0.037). Conclusions　The serum levels of DR-70 and CHI3L1 are high in patients with hepatocellular carcinoma. Their combination with T lymphocyte subsets can evaluate the progression of patients with chronic liver diseases and especially has some value in the early diagnosis of liver tumor.

Key words:

Hepatocellular carcinoma, Hepatitis B virus, T lymphocyte subsets, Chitinase 3-like protein 1, DR-70

摘要：

目的　探讨不同临床分型乙型肝炎病毒（HBV）感染患者外周血T淋巴细胞、壳酶蛋白、纤维蛋白降解复合物（DR-70）表达水平的变化及临床意义，分析肝细胞癌患者T淋巴细胞、壳酶蛋白和DR-70的相关性。方法　回顾性选取2017年9月至2022年9月烟台市奇山医院收治的慢性HBV感染患者173例作为试验组［男114例，女59例，年龄（45.38±12.72）岁］，再根据病情分为乙型肝炎病毒携带者59例、慢性乙型肝炎患者51例、肝硬化患者31例和肝细胞癌患者32例，以同期健康体检者40例作为对照组［男22例，女18例，年龄（39.15±14.95）岁］。运用流式细胞术检测各研究对象外周血T淋巴细胞亚群表达水平，采用酶联免疫吸附试验双抗体夹心法定量检测外周血DR-70水平，应用磁微粒化学发光法检测外周血壳酶蛋白水平。两两比较采用Games-Howell检验，Welch方差用于分析组间方差不齐。Kruskal-Wallis H检验用于非正态分布的计量资料比较，采用χ²检验和Pearson相关分析法进行计数资料组间比较和相关性分析。结果　肝细胞癌组CD3⁺表达水平［（61.43±19.26）%］最低，肝硬化组CD3⁺CD8⁺表达水平［（17.89±9.15）%］最低，与对照组比较，差异均有统计学意义（均P<0.05）；CD3⁺CD4⁺水平在试验组各小组中升高程度不同，肝硬化组最高［（37.16±13.84）%］，与对照组比较，差异均有统计学意义（均P<0.05）。慢性乙型肝炎组、肝硬化组和肝细胞癌组外周血DR-70和壳酶蛋白水平均不同程度升高（均P<0.01），且均在肝细胞癌组中表达水平［（30.11±9.96）mg/L、（213.11±39.76）μg/L］最高（均P<0.01）。肝细胞癌组患者外周血CD3⁺T淋巴细胞表达占比与DR-70水平呈负相关（r=-0.291，P=0.037）。结论　血清DR-70和壳酶蛋白在细胞肝癌中高表达，与T淋巴细胞亚群联合检测可用于评估慢性肝病患者疾病进展程度，有助于慢性乙型肝炎的临床诊疗，特别是对肝脏肿瘤的早期诊断具有较大的应用价值。

关键词:

肝细胞癌, HBV, T淋巴细胞, 壳酶蛋白, DR-70