Liu Lian, Zhang Danyan, Fan Rong, Cheng Shipeng, Yang Jichao, Ma Liyan, Ling Zhiyang, Zhang Yaguang, Hou Jinlin, Wang Xiaomei, Sun Bing, Niu Junqi
Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
Sci China Life Sci. 2025 Feb;68(2):431-440. doi: 10.1007/s11427-024-2691-0. Epub 2024 Sep 27.
It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.
对于患者接受合适的治疗而言，评估肝纤维化的程度和进展至关重要，但其诊断方法仍未满足需求。细胞外基质蛋白1（ECM1）此前已被报道是肝纤维化诱导和进展的关键因素。然而，关于将ECM1用作评估纤维化的生物标志物的应用知之甚少。在四氯化碳诱导的肝纤维化小鼠模型中，本研究表明ECM1随着纤维化程度的逐渐增加而降低。以活检为参照，在247例肝纤维化患者中，血清ECM1水平随着纤维化分期的增加而降低，但在纤维化2期与0 - 1期之间无显著变化。为提高ECM1的性能，将年龄、血小板计数和ECM1浓度相结合计算出EPA（ECM1 - 血小板 - 年龄）评分（范围为0至10）。EPA评分检测F⩾2、F⩾3和F4的受试者工作特征曲线下面积分别为0.6801、0.7377和0.8083，与AST/ALT比值、APRI评分或FIB - 4评分相比，在评估纤维化方面显示出相当或显著更高的诊断性能。在接受抗病毒治疗的乙肝患者中，EPA评分的动态变化取决于肝纤维化发展的状态。EPA评分预测纤维化消退和进展的准确性分别为66.00%和71.43%，而用于监测治疗期间肝纤维化变化的另一种有用方法——肝脏硬度值（LSM）的准确性分别仅为52.00%和7.14%。与健康对照相比，乙肝患者以及丙型肝炎病毒感染、代谢相关脂肪性肝病、酒精性肝病、原发性胆汁性胆管炎和药物性肝损伤患者的血清ECM1水平较低。这些发现表明，ECM1水平降低的个体可能有发生肝损伤的风险，需要进一步检查或医疗护理。总之，含ECM1的EPA评分是用于肝纤维化分期和预测肝纤维化进展的有价值的非侵入性检测方法。此外，单独的ECM1是区分肝损伤患者与健康对照的指标。
