IL-18、IL-37、NLRP3及NK/DC比值在乙型肝炎相关肝硬化中的临床价值

doi:10.3969/j.issn.1673-8640.2022.06.004

摘要/Abstract

摘要：

目的探讨白细胞介素18（IL-18）、白细胞介素37（IL-37）、核苷酸结合寡聚化结构域样受体3（NLRP3）及自然杀伤（NK）细胞/树突状细胞（DC）比值在乙型肝炎（简称乙肝）相关肝硬化中的临床价值。方法选取乙肝相关肝硬化患者129例（乙肝相关肝硬化组,根据ChildPugh分级分为A级49例、B级47例、C级33例）、乙肝患者129例（乙肝组）、体检健康者129名（正常对照组）。据病情进展将129例乙肝相关肝硬化患者分为肝硬化组（98例）和原发性肝癌组（31例）。检测所有对象IL-18、IL-37、NLRP3及NK/DC比值。采用受试者工作特征（ROC）曲线评价IL-18、IL-37、NLRP3及NK/DC比值鉴别诊断乙肝相关肝硬化与原发性肝癌的效能。结果正常对照组、乙肝组和乙肝相关肝硬化组IL-18、IL-37水平及NLRP3相对表达量依次升高（P<0.05）,NK/DC比值依次降低（P<0.05）。ChildPugh分级A级、B级和C级患者IL-18、IL-37水平及NLRP3相对表达量依次升高（P<0.05）,NK/DC比值依次降低（P<0.05）。原发性肝癌组IL-18、IL-37水平及NLRP3相对表达量高于肝硬化组（P<0.05）,NK/DC比值低于肝硬化组（P<0.05）。ROC曲线分析结果显示,NLRP3、IL-18、IL-37、NK/DC比值单项检测及4项指标联合检测鉴别诊断乙肝相关肝硬化与原发性肝癌的曲线下面积（AUC）分别为0.893、0.886、0.860、0.838、0.982。结论 IL-18、IL-37、NLRP3及NK/DC比值与乙肝相关肝硬化的发生、发展密切相关,在乙肝相关肝硬化与原发性肝癌的鉴别诊断中有一定的临床价值。

关键词: 白细胞介素18, 白细胞介素37, 核苷酸结合寡聚化结构域样受体3, 自然杀伤细胞/树突状细胞比值, 乙型肝炎, 肝硬化, 原发性肝癌

Abstract:

Objective To investigate interleukin-18（IL-18）,interleukin-37（IL-37）,nucleotide-binding oligomerization domain-like receptor 3（NLRP3）and natural killer（NK）cell/dendritic cell（DC） ratio in hepatitis B-related liver cirrhosis. Methods A total of 129 patients with hepatitis B-related liver cirrhosis（hepatitis B-related liver cirrhosis group） were enrolled,and according to the ChildPugh classification,they were classified into 49 cases of grade A,47 cases of grade B and 33 cases of grade C. Totally,129 hepatitis B patients（hepatitis B group） and 129 healthy subjects（healthy control group）were enrolled as well. According to the progress of the disease,129 patients with hepatitis B-related liver cirrhosis were classified into hepatitis B-related liver cirrhosis group （98 cases）and primary liver cancer group（31 cases）. All the subjects were determined for IL-18,IL-37,NLRP3 and NK/DC ratio. Receiver operating characteristic（ROC）curve was used to evaluate the efficacy of IL-18,IL-37,NLRP3 and NK/DC ratio in the differential diagnosis of hepatitis B-related liver cirrhosis and primary liver cancer. Results The levels of IL-18,IL-37 and the relative expression of NLRP3 in healthy control group,hepatitis B group and hepatitis B-related liver cirrhosis group were increased in turn（P<0.05）,and the NK/DC ratios were decreased in turn（P<0.05）. The levels of IL-18,IL-37 and the relative expression of NLRP3 in ChildPugh grade A,B and C were increased in turn（P<0.05）,and the NK/DC ratios were decreased in turn（P<0.05）. The levels of IL-18,IL-37 and the relative expression of NLRP3 in primary liver cancer group were higher than those in hepatitis B-related liver cirrhosis group（P<0.05）,and the NK/DC ratio in primary liver cancer group was lower than that in hepatitis B-related liver cirrhosis group（P<0.05）. ROC curve analysis results showed that the areas under curves（AUC）of NLRP3,IL-18,IL-37,NK/DC ratio single determinations and the combined determination for the differential diagnosis of hepatitis B-related liver cirrhosis and primary liver cancer were 0.893,0.886,0.860,0.838 and 0.982,respectively. Conclusions IL-18,IL-37,NLRP3 and NK/DC ratio are related to the occurrence and development of hepatitis B-related liver cirrhosis,and they have clinical values in the differential diagnosis of hepatitis B-related liver cirrhosis and primary liver cancer.

Key words: Interleukin-18, Interleukin-37, Nucleotide-binding oligomerization domain-like receptor 3, Natural killer cell/dendritic cell ratio, Hepatitis B, Liver cirrhosis, Primary liver cancer

中图分类号:

R446.1

吴苏君, 冀恒涛, 彭梦乐. IL-18、IL-37、NLRP3及NK/DC比值在乙型肝炎相关肝硬化中的临床价值[J]. 检验医学, 2022, 37(6): 518-523.

WU Sujun, JI Hengtao, PENG Mengle. Clinical values of IL-18,IL-37,NLRP3 and NK/DC ratio in hepatitis B-related liver cirrhosis[J]. Laboratory Medicine, 2022, 37(6): 518-523.

图/表 6

参考文献 17

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组别	例数	年龄/岁	性别		BMI/ （kg/m²）	吸烟史/例		饮酒史/例		高血压史/例		糖尿病史/例
组别	例数	年龄/岁	男/例	女/例	BMI/ （kg/m²）	有	无	有	无	有	无	有	无
乙肝相关肝硬化组	129	41.5±5.6	69	60	23.14±2.21	21	108	32	97	21	108	15	114
乙肝组	129	41.1±5.2	72	57	23.45±2.54	19	110	31	98	20	109	13	116
正常对照组	129	42.2±6.1	67	62	23.37±2.18	15	114	28	101	16	113	13	116
统计值		1.255	0.395		0.623	1.187		0.374		0.864		0.218
P值		0.286	0.821		0.537	0.552		0.831		0.649		0.896

组别	例数	年龄/岁	性别		BMI/ （kg/m²）	吸烟史/例		饮酒史/例		高血压史/例		糖尿病史/例
组别	例数	年龄/岁	男/例	女/例	BMI/ （kg/m²）	有	无	有	无	有	无	有	无
乙肝相关肝硬化组	129	41.5±5.6	69	60	23.14±2.21	21	108	32	97	21	108	15	114
乙肝组	129	41.1±5.2	72	57	23.45±2.54	19	110	31	98	20	109	13	116
正常对照组	129	42.2±6.1	67	62	23.37±2.18	15	114	28	101	16	113	13	116
统计值		1.255	0.395		0.623	1.187		0.374		0.864		0.218
P值		0.286	0.821		0.537	0.552		0.831		0.649		0.896

组别	例数	NLRP3	IL-18/（pg/mL）	IL-37/（pg/mL）	NK/DC比值
乙肝相关肝硬化组	129	28.54±8.07^*#	452.20±86.24^*#	378.67±61.02^*#	8.48±4.52^*#
乙肝组	129	19.27±6.52^*	221.98±78.83^*	292.61±59.84^*	11.21±2.08^*
正常对照组	129	10.14±2.26	132.43±11.56	102.48±14.87	14.38±2.24
F值		290.54	763.953	1 027.095	113.323
P值		<0.001	<0.001	<0.001	<0.001

组别	例数	NLRP3	IL-18/（pg/mL）	IL-37/（pg/mL）	NK/DC比值
乙肝相关肝硬化组	129	28.54±8.07^*#	452.20±86.24^*#	378.67±61.02^*#	8.48±4.52^*#
乙肝组	129	19.27±6.52^*	221.98±78.83^*	292.61±59.84^*	11.21±2.08^*
正常对照组	129	10.14±2.26	132.43±11.56	102.48±14.87	14.38±2.24
F值		290.54	763.953	1 027.095	113.323
P值		<0.001	<0.001	<0.001	<0.001

ChildPugh分级	例数	NLRP3	IL-18/（pg/mL）	IL-37/（pg/mL）	NK/DC比值
A级	49	20.45±3.12	344.21±79.97	300.43±53.22	10.37±1.21
B级	47	30.03±5.94^*	476.56±87.94^*	417.44±45.21^*	8.11±1.29^*
C级	33	37.94±7.72^*#	543.87±79.87^*#	434.52±51.15^*#	6.22±2.01^*#
F值		283.758	194.719	275.154	233.067
P值		<0.001	<0.001	<0.001	<0.001