血清preS1、DNMT1、TIMP-1水平与CHB肝纤维化分期的关系及对进展期肝纤维化的评估价值-东南大学学报医学版

血清preS1、DNMT1、TIMP-1水平与CHB肝纤维化分期的关系及对进展期肝纤维化的评估价值

单位：1. 邯郸市第一医院感染性疾病科, 河北邯郸 056000;
2. 邯郸市第一医院消化内科, 河北邯郸 056000

关键词：慢性乙型肝炎血清前S1蛋白 DNA甲基转移酶1 基质金属蛋白酶组织抑制因子-1 肝纤维化相关性

分类号：R512.62;R575.1

出版年·卷·期（页码）：2026·45·第二期（220-228）

摘要：

目的:探讨血清前S1蛋白(preS1)、DNA甲基转移酶1(DNMT1)、基质金属蛋白酶组织抑制因子-1(TIMP-1)水平与慢性乙型肝炎(CHB)肝纤维化分期的关系及对进展期肝纤维化的评估价值。方法:回顾性选取邯郸市第一医院2022年1月至2024年8月CHB患者206例作为研究组,取同期健康体检者103名作为对照组。比较两组及研究组不同肝纤维化分期患者血清preS1、DNMT1、TIMP-1水平,分析血清preS1、DNMT1、TIMP-1水平与肝纤维化分期的相关性,将研究组分为进展期亚组(进展期肝纤维化)与非进展期亚组(非进展期肝纤维化),比较不同亚组患者临床资料及血清preS1、DNMT1、TIMP-1水平,采用Logistic回归及平滑曲线拟合分析各指标与进展期肝纤维化的相关性,受试者工作特征(ROC)曲线分析三者对进展期肝纤维化的评估价值。结果:研究组血清preS1、DNMT1、TIMP-1水平高于对照组(P＜0.05);研究组不同肝纤维化分期患者血清preS1、DNMT1、TIMP-1水平比较,差异有统计学意义(P＜0.05),血清preS1、DNMT1、TIMP-1水平在S1、S2、S3、S4期患者中呈逐渐升高趋势(P＜0.05);血清preS1、DNMT1、TIMP-1水平与肝纤维化分期呈正相关(P＜0.05)。进展期亚组饮酒比例、HBV基因分型C型比例、HBV-DNA病毒载量、肝组织的炎症活动程度高于非进展期亚组,规律抗病毒治疗比例低于非进展期亚组(P＜0.05)。血清preS1、DNMT1、TIMP-1是CHB肝纤维化程度的独立影响因素,且各指标与肝纤维化程度呈显著线性相关(P＜0.05);血清preS1、DNMT1、TIMP-1联合评估肝纤维化程度的曲线下面积(AUC)高于三者单独评估(P＜0.05)。结论:血清preS1、DNMT1、TIMP-1水平与CHB患者肝纤维化程度存在明显相关性,三者联合可为临床评估患者肝纤维化程度提供参考。

Objective: To investigate the relationship between serum preS1 protein(preS1), DNA methyltransferase 1(DNMT1), tissue inhibitor of metalloproteinase-1(TIMP-1) levels and liver fibrosis stage of chronic hepatitis B(CHB) and their evaluation value of advanced liver fibrosis. Methods: A total of 206 patients with CHB from January 2022 to August 2024 in the Handan First Hospital were retrospectively selected as the study group,103 healthy subjects in the same period were selected as the control group. The levels of serum preS1, DNMT1 and TIMP-1 in the two groups and the patients with different stages of liver fibrosis in the study group were compared. The correlation between serum preS1, DNMT1, TIMP-1 and liver fibrosis stage was analyzed. The study group was divided into advanced subgroup(advanced liver fibrosis) and non-advanced subgroup(non-advanced liver fibrosis). The clinical data and serum preS1, DNMT1 and TIMP-1 levels in different subgroups were compared. Logistic regression analysis and smooth curve fitting were used to analyze the correlation between each index and advanced liver fibrosis. The receiver operating characteristic(ROC) curve was used to analyze the value of the three in the evaluation of advanced liver fibrosis. Results: The levels of preS1, DNMT1, and TIMP-1 in the study group were higher than those in the control group(P<0.05). There were significant differences in the levels of serum preS1, DNMT1 and TIMP-1 in patients with different stages of liver fibrosis in the study group(P<0.05). The levels of serum preS1, DNMT1 and TIMP-1 were gradually increased in patients with stage S1, S2, S3, and S4 in the study group(P<0.05). Serum preS1, DNMT1 and TIMP-1 were positively correlated with liver fibrosis stage(P<0.05). The proportion of alcohol consumption, the proportion of HBV genotype C, HBV-DNA viral load and the degree of inflammatory activity of liver tissue in the advanced subgroup were higher than those in the non-advanced subgroup, and the proportion of regular antiviral treatment was lower than that in the non-advanced subgroup(P<0.05). Serum preS1, DNMT1, and TIMP-1 were independent factors affecting the degree of liver fibrosis in CHB, and each indicator was significantly linearly correlated with the degree of liver fibrosis(P<0.05). The area under the curve(AUC) of the combined assessment of serum preS1, DNMT1, and TIMP-1 for evaluating the degree of liver fibrosis was higher than that of the three individual assessments(P<0.05). Conclusion: The levels of serum preS1, DNMT1, and TIMP-1 are significantly correlated with the degree of liver fibrosis in patients with CHB, and the combination of the three can provide a reference for clinical evaluation of the degree of liver fibrosis in patients.

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