熊去氧胆酸治疗原发性胆汁性胆管炎患者血清MMP-1和IL-6水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2025.04.024

摘要/Abstract

摘要： 目的探讨影响熊去氧胆酸(UDCA)治疗原发性胆汁性胆管炎(PBC)患者血清金属基质蛋白酶1(MMP-1)和白细胞介素6(IL-6)水平变化及其临床意义。方法 2022年1月～2024年1月我院诊治的疗52例PBC患者,均接受UDCA治疗6个月,另选择同期健康体检者50例作为对照,采用ELISA法检测血清MMP-1和IL-6水平,采用多因素Logistic回归分析影响治疗应答的因素,应用受试者工作特征(ROC)曲线评估血清MMP-1和IL-6水平预测治疗应答的效能。结果治疗前PBC患者血清MMP-1水平为(8.6±1.9)ng/mL,显著低于健康人【(12.1±2.8)ng/mL,P<0.05】,血清IL-6水平为(9.8±2.4)pg/mL,显著高于健康人【(6.1±1.5)pg/mL,P<0.05】;在治疗6个月末,PCB患者血清MMP-1水平升高,而血清IL-6水平降低(P<0.05);17例Ludwig Ⅲ/Ⅳ期PBC患者基线血清MMP-1水平显著低于,而血清IL-6水平显著高于35例Ludwig Ⅰ/Ⅱ期PBC患者(P<0.05);本组获得完全应答(CR)者31例(59.6%),不完全应答(ICR)者21例(40.4%);ICR组Ludwig Ⅲ/Ⅳ期(76.2%对3.2%)、合并脂肪肝(47.6%对9.7%)和血清AMA阴性占比(38.1%对12.9%)及血清总胆红素【(37.6±11.4)μmol/L对(19.1±1.6)μmol/L】、MMP-1【(7.6±1.5)ng/mL对(9.3±1.7)ng/mL】和IL-6水平【(11.4±2.8)pg/mL对(9.0±1.8)pg/mL】与CR组比,存在显著性差异(P<0.05);多因素Logistic回归分析显示,Ludwig Ⅲ/Ⅳ期、血清胆红素水平高、MMP-1水平降低和IL-6水平升高均为影响接受UDCA治疗的PBC患者短期应答的因素(P<0.05);ROC分析显示,血清MMP-1水平低于8.0 ng/mL或/和IL-6水平高于10.6pg/mL预示治疗应答不完全(P<0.05)。结论监测接受UDCA治疗的PBC患者血清MMP-1和 IL-6水平变化可能有助于及时预判治疗应答,值得深入研究。

关键词: 原发性胆汁性胆管炎, 熊去氧胆酸, 金属基质蛋白酶1, 白细胞介素6, 治疗

Abstract: Objective The purpose of this study was to explore implication of serum matrix metalloproteinase 1 (MMP-1) and interleukin-6 (IL-6) level changes in patients with primary biliary cholangitis (PBC)during ursodeoxycholic acid (UDCA) treatment. Methods 52 patients with PBCand 50 healthyindividuals were enrolled in our hospital between January 2022 and January 2024, and all patients received UDCA treatment for six months. Serum MMP-1 and IL-6 levels were detected by ELISA,multivariate Logistic regression analysis was applied to reveal impacting factors, and receiver operating characteristic (ROC) curve was used to evaluate predicting efficacy. Results At presentation, serum MMP-1 level in patients with PBC was (8.6±1.9)ng/mL, much lower than [(12.1±2.8)ng/mL, P<0.05], while serum IL-6 level was (9.8±2.4)pg/mL, much higher than [(6.1±1.5)pg/mL, P<0.05] in the healthy individuals; by end of six month treatment, serum MMP-1 level increased and serum IL-6 level decreased (P<0.05)in patients with PBC; baseline serum MMP-1 level in 17 patients with Ludwig phase Ⅲ/Ⅳ was much lower, while serum IL-6 level was much higher than in 35 patients with Ludwig phase Ⅰ/Ⅱ (P<0.05); complete response (CR) rate in our series was 59.6%(31/52) by end of six month observation; percentages of Ludwig phase Ⅲ/Ⅳ(76.2% vs. 3.2%), concomitant fatty liver (47.6% vs. 9.7%) and serum anti-mitochondrial antibody negative (38.1% vs. 12.9%), as well as total serum bilirubin (TSB) levels [(37.6±11.4)μmol/Lvs. (19.1±1.6)μmol/L], MMP-1[(7.6±1.5)ng/mL vs. (9.3±1.7)ng/mL] and IL-6 levels [(11.4±2.8)pg/mL vs. (9.0±1.8)pg/mL] in patients with incomplete response (ICR) were significantly different compared to in those with CR (P<0.05); multivariate Logistic regression analysis showed that Ludwig phase Ⅲ/Ⅳ, elevated TSB and IL-6 and decreased serum MMP-1 levels were all the independent risk factors impacting response to UDCA treatment(P<0.05);ROC analysis demonstrated that serum MMP-1 level lower than 8.0 ng/mL or serum IL-6 level higher than 10.6pg/mL hinted poor response to UDCA treatment (P<0.05). Conclusion Surveillance of serum MMP-1 and IL-6 level changes might help predict response to UDCA treatment in patients with PBC, which warrants further clinical investigation.

Key words: Primary biliary cholangitis, Ursodeoxycholic acid, Matrix metalloproteinase 1, Interleukin 6, Short-term response, Therapy

彭志芳, 吴莉, 盛秀红. 熊去氧胆酸治疗原发性胆汁性胆管炎患者血清MMP-1和IL-6水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(4): 573-576.

Peng Zhifang, Wu Li, Sheng Xiuhong. Changes of serum MMP-1 and IL-6 levels in patients with primary biliary cholangitis during ursodeoxycholic acid treatment[J]. Journal of Practical Hepatology, 2025, 28(4): 573-576.

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熊去氧胆酸治疗原发性胆汁性胆管炎患者血清MMP-1和IL-6水平变化及其临床意义探讨^*

Changes of serum MMP-1 and IL-6 levels in patients with primary biliary cholangitis during ursodeoxycholic acid treatment

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