慢性乙型肝炎患者血清MMP-1、MMP-2、TIMP-1和HIF-1α变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2024.03.003

摘要/Abstract

摘要： 目的研究检测慢性乙型肝炎(CHB)患者血清基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶组织抑制因子-1(TIMP-1)和缺氧诱导因子-1α(HIF-1α)水平诊断显著性肝纤维化的效能。方法 2019年1月～2022年6月我院收治的CHB患者73例和健康体检者50名,采用ELISA法检测血清MMP-1、MMP-2、TIMP-1和HIF-1α水平,CHB患者接受肝活检,以>=S2为显著性肝纤维化。采用受试者工作特征曲线(ROC)分析血清指标诊断肝纤维化的效能。结果 CHB组血清MMP-1水平为(9.3±2.7)μg/L,显著低于对照组【(12.7±3.3)μg/L,P<0.05】,而血清MMP-2、TIMP-1和HIF-1α水平分别为(387.2±54.2)mg/L、(296.3±72.9)μg/L和(68.9±11.3)μg/L,均显著高于对照组【分别为(251.6±33.5)mg/L、(142.2±23.6)μg/L和(35.1±7.6)μg/L,P<0.05】;经肝穿刺活检组织病理学检查,在73例CHB患者中发现肝纤维化S0～S1期18例、S2期22例、S3期19例和S4期14例;S4期患者血清MMP-1水平为(6.3±1.8)μg/L,而血清MMP-2、TIMP-1和HIF-1α水平分别为(516.7±39.2)mg/L、(373.6±55.4)μg/L和(96.8±10.8)μg/L,S3期患者血清MMP-1水平为(7.9±2.2)μg/L,而血清MMP-2、TIMP-1和HIF-1α水平分别为(482.5±48.3)mg/L、(324.7±59.6)μg/L和(87.5±13.9)μg/L,与S0～S1期或S2期比,差异显著(P<0.05);经ROC分析,血清MMP-1、MMP-2、TIMP-1和HIF-1α水平诊断CHB患者显著性肝纤维化的截断点分别为10.9 μg/L、309.4 mg/L、212.3 μg/L和54.1 μg/L,其曲线下面积分别为0.835(0.752～0.918)、0.948(0.917～0.979)、0.955(0.928～0.982)和0.919(0.877～0.961),以血清TIMP-1和HIF-1α水平诊断效能较优。结论检测CHB患者血清TIMP-1和HIF-1α或/和MMP-1水平可以帮助筛查显著性肝纤维化,具有一定的临床指导意义。

关键词: 慢性乙型肝炎, 肝纤维化, 基质金属蛋白酶, 基质金属蛋白酶组织抑制因子, 缺氧诱导因子-1α, 诊断

Abstract: Objective This study was to assess the implications of serum matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and hypoxia inducible factor-1α (HIF-1α) levels in patients with chronic hepatitis B (CHB). Methods 73 patients with CHB and 50 healthy persons were included in this study between January 2019 and June 2022, and serum MMP-1, MMP-2, TIMP-1 and HIF-1α levels were detected by ELISA. All patients with CHB underwent liver biopsies, and the significant liver fibrosis (SLF) was defined as equal to or greater than S2. The diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUROC). Results Serum MMP-1 level in patients with CHB was (9.3±2.7)μg/L, much lower than [(12.7±3.3)μg/L, P<0.05], while serum MMP-2, TIMP-1 and HIF-1α levels were (387.2±54.2)mg/L, (296.3±72.9)μg/L and (68.9±11.3)μg/L, all significantly higher than [(251.6±33.5)mg/L, (142.2±23.6)μg/L and (35.1±7.6)μg/L, respectively, P<0.05] in healthy individuals; the liver histopathological examination showed liver fibrosis S0-S1 in 18 cases, S2 in 22, S3 in 19 cases and S4 in 14 cases (>=S2 in 55 cases); serum MMP-1 level in patients with S4 liver fibrosis was (6.3±1.8)μg/L, while serum MMP-2, TIMP-1 and HIF-1α levels were (516.7±39.2)mg/L, (373.6±55.4)μg/L and (96.8±10.8)μg/L, and serum MMP-1 level in patients with S3 was (7.9±2.2)μg/L, while serum MMP-2, TIMP-1 and HIF-1α levels were (482.5±48.3)mg/L, (324.7±59.6)μg/L and (87.5±13.9)μg/L, both significantly different as compared to in patients with S0-S1 or with S2(P<0.05); the ROC analysis demonstrated that the AUCs were 0.835(0.752-0.918), 0.948(0.917-0.979), 0.955(0.928-0.982) and 0.919(0.877-0.961), when serum MMP-1, MMP-2, TIMP-1 and HIF-1α levels equal to 10.9 μg/L, 309.4 mg/L, 212.3 μg/L and 54.1 μg/L were set as the cut-off-value in predicting SLF in patients with CHB, superior for serum TIMP-1 and HIF-1α to the other two. Conclusion Serum TIMP-1 and HIF-1α, and/or MMP-1 levels might be used to screen liver fibrosis in patients with CHB, and needs further investigation.

Key words: Hepatitis B, Liver fibrosis, Matrix metalloproteinase, Tissue inhibitor of matrix metalloproteinases, Hypoxia inducible factor-1 α, Diagnosis

虞珊珊, 张业婷, 王元鹏, 袁静文, 肖立. 慢性乙型肝炎患者血清MMP-1、MMP-2、TIMP-1和HIF-1α变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2024, 27(3): 329-332.

Yu Shanshan, Zhang Yeting, Wang Yuanpeng, et al. Changes of serum MMP-1, MMP-2, TIMP-1 and HIF-1α levels in patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2024, 27(3): 329-332.

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慢性乙型肝炎患者血清MMP-1、MMP-2、TIMP-1和HIF-1α变化及其临床意义探讨^*

Changes of serum MMP-1, MMP-2, TIMP-1 and HIF-1α levels in patients with chronic hepatitis B

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