IL-33、TIMP-1、MMP-2与慢性乙型肝炎肝硬化预后的相关性分析

张雨婷; 沈炜; 顾佳萍

doi:10.16766/j.cnki.issn.1674-4152.003874

IL-33、TIMP-1、MMP-2与慢性乙型肝炎肝硬化预后的相关性分析

doi: 10.16766/j.cnki.issn.1674-4152.003874

浙江大学医学院附属第二医院临平院区感染科，浙江杭州 311100

基金项目:

浙江省医药卫生科技计划项目 2024KY1462

详细信息

通讯作者:
张雨婷，E-mail：xyzab18072889033@163.com

中图分类号: R512.62 R575.2
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- 被引次数: 0
出版历程
- 收稿日期: 2024-03-31
- 网络出版日期: 2025-03-27

The correlation between IL-33, TIMP-1, MMP-2 and prognosis of chronic hepatitis B cirrhosis

Department of Infectious, Linping Campus, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 311100, China

摘要

摘要: 目的探讨慢性乙型肝炎肝硬化(HBC)不同进展程度血清白介素-33(IL-33)、基质金属蛋白酶组织抑因子1(TIMP-1)、基质金属蛋白酶2(MMP-2)变化, 并分析血清IL-33、TIMP-1、MMP-2水平与不同程度肝硬化的关系及其对预后的预测价值。方法选取2021年1月-2022年12月期间浙江大学医学院附属第二医院临平院区收治的HBC代偿期患者60例(代偿组)、HBC失代偿期患者60例(失代偿组)以及未合并肝硬化的慢性乙型肝炎患者60例(慢性组)。分析血清IL-33、TIMP-1、MMP-2水平与肝硬化发生的关系, 绘制ROC曲线评估血清IL-33、TIMP-1、MMP-2对HBC预后的价值。结果失代偿组血清IL-33、TIMP-1、MMP-2水平高于代偿组及慢性组(P < 0.05), 代偿组血清IL-33、TIMP-1、MMP-2水平高于慢性组(P < 0.05);血清IL-33、TIMP-1、MMP-2水平与慢性乙型肝炎患者肝硬化的发生呈正相关关系(r=0.784、0.691、0.698, 均P < 0.001);ROC曲线显示, 血清IL-33、TIMP-1、MMP-2水平预测HBC患者预后不良的灵敏度分别为81.25%、81.25%、84.37%, 特异度分别为69.32%、68.18%、71.59%, AUC分别为0.762、0.734、0.830。结论血清IL-33、TIMP-1、MMP-2在HBC患者中高表达, 且与肝硬化的发生呈正相关关系, 血清MMP-2对患者预后不良的预测价值更高。
- 慢性乙型肝炎 /
- 肝硬化 /
- 预后 /
- 相关性
Abstract: Objective To investigate the changes of serum interleukin-33(IL-33), matrix metalloproteinase-1(TIMP-1), and matrix metalloproteinase-2(MMP-2) in patients with chronic hepatitis B cirrhosis (HBC).The relationship between IL-33, TIMP-1, and MMP-2 levels and different degrees of cirrhosis and their prognostic value were analyzed. Methods From January 2021 to December 2022, 60 patients with HBC compensation (compensation group), 60 patients with HBC decompensation (decompensation group), and 60 patients with chronic hepatitis B without liver cirrhosis (chronic group) were selected.To analyze the relationship between serum levels of IL-33, TIMP-1, and MMP-2 and the occurrence of cirrhosis.The value of serum IL-33, TIMP-1, and MMP-2 on the prognosis of patients with chronic hepatitis B cirrhosis was evaluated by the ROC curve. Results The serum levels of IL-33, TIMP-1, and MMP-2 in the decompensated group were higher than those in the compensated and chronic groups (P < 0.05).The levels of IL-33, TIMP-1, and MMP-2 in the compensated group were higher than those in the chronic group (P < 0.05).Serum levels of IL-33, TIMP-1, and MMP-2 in 180 patients with chronic hepatitis B were positively correlated with cirrhosis (r=0.784, 0.691, 0.698, all P < 0.001).ROC results showed that the sensitivity of serum IL-33, TIMP-1, and MMP-2 levels to detect poor prognosis in patients with chronic hepatitis B cirrhosis were 81.25%, 81.25%, and 84.37%, and the specificity were 69.32%, 68.18%, and 71.59%, respectively.The AUC were 0.762, 0.734, and 0.830, respectively. Conclusion Serum IL-33, TIMP-1, and MMP-2 are highly expressed in patients with chronic hepatitis B cirrhosis, and they are positively correlated with the occurrence of cirrhosis.Especially, serum MMP-2 has a higher predictive value for poor prognosis in patients.
- Chronic hepatitis B /
- Liver cirrhosis /
- Prognosis /
- Correlation

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图 1 血清IL-33、TIMP-1、MMP-2对HBC患者预后不良的ROC曲线

Figure 1. ROC curve of serum IL-33, TIMP-1 and MMP-2 for poor prognosis in HBC patients

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表 1 3组慢性乙型肝炎患者血清IL-33、TIMP-1、MMP-2水平比较(x±s)

Table 1. Comparison of serum levels of IL-33, TIMP-1 and MMP-2 in 3 groups of chronic hepatitis B patients(x±s)

组别	例数	IL-33(pg/mL)	TIMP-1(ng/mL)	MMP-2(ng/mL)
失代偿组	60	559.26±69.75	188.26±28.74	415.78±55.26
代偿组	60	476.42±68.55^a	155.52±23.22^a	360.62±43.28^a
慢性组	60	351.47±62.92^ab	131.19±20.82^ab	305.74±39.46^ab
F值		145.643	82.077	84.038
P值		＜0.001	＜0.001	＜0.001
注：与失代偿组比较，^aP < 0.05；与代偿组组比较，^bP < 0.05。

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表 2 预后良好组与预后不良组HBC患者一般资料比较

Table 2. Comparison of general data of HBC patients in good prognosis group and poor prognosis group

项目	预后良好组 (n=88)	预后不良组 (n=32)	统计量	P值
性别[例(%)]			0.436^a	0.509
男性	58(65.91)	19(59.38)
女性	30(34.09)	13(40.62)
年龄(x±s, 岁)	54.05±8.12	54.85±8.23	0.476^b	0.635
BMI(x±s)	23.12±4.23	23.78±4.56	0.740^b	0.461
ALT(x±s, U/L)	46.62±5.47	51.89±7.23	4.267^b	＜0.001
AST(x±s, U/L)	38.94±5.12	42.78±6.22	3.425^b	＜0.001
ALB(x±s, g/L)	28.74±4.23	29.15±4.22	0.470^b	0.639
TBIL(x±s, mg/dL)	1.20±0.28	1.42±0.32	3.662^b	＜0.001
总蛋白(x±s, g/L)	58.96±7.62	47.88±7.23	7.138^b	＜0.001
SCr(x±s, mg/dL)	1.51±0.33	1.60±0.41	1.236^b	0.219
BUN(x±s, mmol/L)	6.89±1.22	7.03±1.41	0.533^b	0.595
凝血酶原时间(x±s, s)	14.79±3.42	15.18±3.67	0.542^b	0.589
IL-33(x±s, pg/mL)	502.28±65.74	564.96±58.62	4.748^b	＜0.001
TIMP-1(x±s, ng/mL)	164.85±35.69	192.74±32.15	3.883^b	＜0.001
MMP-2(x±s, ng/mL)	372.84±40.28	429.25±42.56	6.683^b	＜0.001
MELD评分[例(%)]			3.064^c	0.002
高危	13(14.77)	13(40.63)
中危	35(39.77)	12(37.50)
低危	40(45.45)	7(21.88)
Child Pugh分级[例(%)]			13.169^a	＜0.001
B级	60(68.18)	10(31.25)
C级	28(31.82)	22(68.75)
消化道出血[例(%)]	11(12.50)	8(25.00)	2.751^a	0.097
肝肾综合征[例(%)]	8(9.09)	5(15.63)	1.037^a	0.308
肝性脑病[例(%)]	9(10.23)	5(15.63)	0.663^a	0.415
腹水[例(%)]	79(89.77)	28(87.50)	0.125^a	0.723
抗纤维化药[例(%)]	62(70.45)	25(78.13)	0.693^a	0.405
保肝药物[例(%)]	78(88.64)	27(84.38)	0.390^a	0.533
电解质紊乱[例(%)]	30(34.09)	15(46.88)	1.636^a	0.201
肝病家族史[例(%)]	20(22.73)	10(31.25)	0.909^a	0.340
高血压[例(%)]	35(39.77)	18(56.25)	2.584^a	0.108
糖尿病[例(%)]	30(34.09)	15(46.88)	1.636^a	0.201
高脂血症[例(%)]	28(31.82)	13(40.63)	0.809^a	0.368
吸烟史[例(%)]	29(32.95)	15(46.88)	1.958^a	0.162
饮酒史[例(%)]	22(25.00)	17(53.13)	8.462^a	0.004
注：^a为χ²值，^b为t值，^c为Z值。

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表 3 HBC患者预后不良影响因素的多因素分析

Table 3. Multivariate analysis of adverse prognostic factors in patients with HBC

变量	B	SE	Waldχ²	P值	OR值	95% CI
IL-33	0.740	0.317	5.449	＜0.001	2.096	1.246~3.796
TIMP-1	0.691	0.296	5.449	＜0.001	1.996	1.123~4.673
MMP-2	0.664	0.199	11.133	＜0.001	1.943	1.267~4.375
ALT	0.710	0.396	3.215	0.038	2.034	1.473~3.854
AST	0.487	0.223	4.769	＜0.001	1.627	1.082~3.276
TBIL	0.529	0.258	4.204	＜0.001	1.697	1.127~2.472
总蛋白	-0.702	0.243	8.346	< 0.001	0.496	0.255~0.934
MELD评分	0.612	0.382	2.377	0.064	1.802	1.125~3.256
Child Pugh分级	0.589	0.352	3.564	0.022	1.844	1.130~3.720
饮酒	0.689	0.492	1.961	0.089	1.992	1.243~3.186

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表 4 血清IL-33、TIMP-1、MMP-2对HBC患者预后不良的ROC曲线分析结果

Table 4. ROC curve analysis of serum IL-33, TIMP-1 and MMP-2 for poor prognosis of HBC patients

项目	最佳截断点	灵敏度(%)	特异度(%)	准确度(%)	AUC	95% CI
IL-33	＞525.67	81.25(26/32)	69.32(61/88)	72.50(87/120)	0.762	0.676~0.835
TIMP-1	＞175.65	81.25(26/32)	68.18(60/88)	71.67(86/120)	0.734	0.646~0.811
MMP-2	＞390.30	84.37(27/32)	71.59(63/88)	75.00(90/120)	0.830	0.751~0.892

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