不同临床类型慢性HBV感染患者血清ADA、miR-181a、NK细胞与HBV DNA载量的关系

摘要/Abstract

摘要： 目的探讨不同临床类型慢性HBV感染患者HBV DNA载量、腺苷脱氨酶(ADA)、miR-181a、自然杀伤(NK)细胞的表达,并分析ADA、miR-181a、NK细胞与HBV DNA载量的关系。方法回顾性选取2017年1月至2020年9月收治的144例HBV感染患者作为研究对象。以疾病类型分为HBV携带者(ASC)、慢性乙型肝炎(CHB)、乙型肝炎肝硬化(LC)以及HBV相关性肝细胞癌(HBV-HCC),其中ASC 37例、CHB 43例、LC 31例、HBV-HCC 33例;另择同时期体检正常的30例健康人作为对照组。收集受试者HBV DNA、ADA、miR-181a及NK细胞等数据,并行分析。结果 CHB组HBV DNA载量为(6.07±0.93)copy/mL,显著高于ASC组、LC组、HBV-HCC组的(5.63±0.82)/mL、(5.38±0.73)copy/mL、(4.53±0.42)copy/mL(P<0.05),HBV-HCC组HBV DNA载量水平显著低于ASC组、LC组(P<0.05);HBV-HCC组患者ADA(49.85±7.23)U/L,显著高于ASC组、CHB组、LC组、对照组的(13.28±3.27)U/L、(21.82±4.83)U/L、(35.83±5.59)U/L、(9.43±2.31)U/L(P<0.05),LC组ADA显著高于ASC组、对照组(P<0.05),CHB组ADA显著高于ASC组、对照组(P<0.05),ASC组ADA显著高于对照组(P<0.05);HBV-HCC组NK细胞(4.05±0.73)%,显著低于ASC组、CHB组、LC组、对照组的(9.42±2.51)%、(8.43±1.08)%、(5.89±1.34)%、(11.04±2.87)%(P<0.05),LC组NK细胞显著低于ASC组、CHB组、对照组(P<0.05),CHB组NK细胞显著低于ASC组、对照组(P<0.05),ASC组NK细胞显著低于对照组(P<0.05);CHB组miR-181a相对表达量为(0.71±0.13)2^-ΔΔCt,显著低于ASC组、LC组、HBV-HCC组、对照组的(0.94±0.08)2^-ΔΔCt、(0.94±0.08)2^-ΔΔCt、(1.23±0.13)2^-ΔΔCt、(0.98±0.04)2^-ΔΔCt(P<0.05),HBV-HCC组miR-181a相对表达量显著高于ASC组、LC组、对照组(P<0.05)。在ASC、CHB、LC、HBV-HCC患者中,ADA与HBV DNA载量均呈正相关(r=0.752、0.668、0.413、0.639,P<0.05),NK细胞与HBV DNA载量呈负相关(r=-0.631、-0.473、-0.507、-0.434,P<0.05);miR-181a在CHB患者与HBV DNA载量呈负相关(r=-0.613,P<0.05),在HBV-HCC患者与病毒载量HBV DNA呈正相关性(r=0.510,P<0.05)。结论在ASC、CHB、LC、HBV-HCC患者中,血清ADA水平与HBV DNA水平均呈正相关,而NK细胞与HBV DNA水平呈负相关,miR-181a与CHB患者HBV DNA呈负相关,与HBV-HCC患者HBV DNA呈正相关。

关键词: 乙型肝炎病毒, HBV DNA, 腺苷脱氨酶, miR-181a, 自然杀伤细胞

Abstract: Objective To investigate the changes of hepatitis B virus (HBV)-DNA load, adenosine deaminase (ADA), miR-181a, natural killer (NK) cells in patients with different clinical types of hepatitis B after HBV infection, and the relationship between ADA, miR-181a, NK cells and HBV DNA load. Methods One hundred and forty-four patients with HBV infection admitted to our hospital from January 2017 to September 2020 were retrospectively selected as the research objects. According to disease types, they were divided into HBV carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC) and HBV-associated hepatocellular carcinoma (HBV-HCC) groups, of which 37 cases were ASC, 43 cases were CHB, 31 cases were LC and 33 cases were HBV-HCC. Another 30 healthy people with normal physical examination during the same period were selected as a control group. Data of HBV DNA load, serum ADA level, plasma miR-181a level, and the percentage of NK cells in peripheral blood mononuclear cells (PBMC) were collected for comparative analysis. Results HBV DNA load in CHB group was (6.07±0.93) copy/mL, which was significantly higher than those of (5.63±0.82) copy/mL, (5.38±0.73) copy/mL and (4.53±0.42) copy/mL in ASC group, LC group and HBV-HCC group, respectively (P<0.05). HBV DNA load in HBV-HCC group was significantly lower than those in ASC group and LC group (P<0.05). The ADA level of HBV-HCC patients was (49.85±7.23) U/L, which was significantly higher than those of (13.28±3.27) U/L, (21.82±4.83) U/L, (35.83±5.59) U/L, (9.43±2.31) U/L in the ASC, CHB group, LC group and control group, respectively (P<0.05). The ADA level of LC group and CHB group were significantly higher than those in the ASC group and control group (P<0.05), and the ADA level in ASC group was significantly higher than that of the control group (P<0.05). The percentage of NK/PBMC cells in HBV-HCC group was (4.05±0.73)%, which was significantly lower than those of (9.42±2.51)%, (8.43±1.08)%, (5.89±1.34)%, (11.04 ±2.87)% in the ASC group, CHB group, LC group and control group, respectively (P<0.05). The percentage of NK cells in LC group was significantly lower than those of the ASC group, CHB group and control group (P<0.05). The percentage of NK cells in CHB group was significantly lower than those of the ASC group and control group (P<0.05), and the percentage of NK cells in ASC group was significantly lower than that of the control group (P<0.05). The relative expression level of miR-181a in CHB group was (0.71±0.13) 2^-ΔΔCt, which was significantly lower than those of (0.94±0.08)2^-ΔΔCt, (0.94±0.08) 2^-ΔΔCt, (1.23±0.13) 2^-ΔΔCt, (0.98±0.04)2^-ΔΔCt in the ASC group, LC group, HBV-HCC group and control group, respectively (P<0.05), The relative expression level of miR-181a in the HBV-HCC group was significantly higher than those of the ASC group, LC group and control group (P<0.05). In ASC, CHB, LC and HBV-HCC patients, ADA was positively correlated with HBV DNA load (r=0.752, 0.668, 0.413, 0.639, P<0.05), while NK cells were negatively correlated with HBV DNA load (r=-0.631, -0.473, -0.507, -0.434, P<0.05). There was a negative correlation between miR-181a level and HBV DNA load in CHB patients (r=-0.613, P<0.05), and a positive correlation between miR-181a level and HBV DNA viral load in HBV-HCC patients (r=0.510, P<0.05). Conclusion In ASC, CHB, LC and HBV-HCC patients, serum ADA level was positively, whereas the percentage of NK cells was negatively correlated with HBV DNA viral load. The miR-181a level was negatively correlated with HBV DNA load in CHB patients but positively correlated with that in HBV-HCC patients.

Key words: Hepatitis B virus, HBV DNA load, adenosine deaminase, miR-181a, natural killer cells

李成, 张伟, 陈曲, 张磊, 赵秋剑, 李耀妮. 不同临床类型慢性HBV感染患者血清ADA、miR-181a、NK细胞与HBV DNA载量的关系[J]. 肝脏, 2021, 26(11): 1231-1235.

LI Cheng, ZHANG Wei, CHEN Qu, ZHANG Lei, ZHAO Qiu-jian, LI Yao-ni. Relationship between serum ADA, miR-181a, NK cells and HBV DNA load in patients with different clinical types of hepatitis B infection[J]. Chinese Hepatolgy, 2021, 26(11): 1231-1235.

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