血清Mac⁃2结合蛋白对血吸虫病肝纤维化严重程度的诊断价值

摘要/Abstract

摘要： 目的　评估血清Mac⁃2结合蛋白（Mac⁃2 binding protein，M2BP）对血吸虫病肝纤维化严重程度的诊断价值，为血吸虫病肝纤维化的无创诊断和病情监测提供参考。方法　2019—2020年在江西省庐山市新华村抽取234名既往血吸虫感染者作为调查对象，并采集其血清样本，共234份。对调查对象进行肝脏B超检查，根据检查结果将血清样本分为血吸虫病肝纤维化0、Ⅰ、Ⅱ级和Ⅲ级4个级别，各级别再按7∶3的比例将样本随机分为受试者工作特征（receiver operating characteristic，ROC）曲线组和效能评估组。采用酶联免疫吸附法检测不同血吸虫病肝纤维化分级血清样本中M2BP浓度，并进行方差分析和Spearman相关性分析。对不同血吸虫病肝纤维化分级血清样本ROC组M2BP浓度进行ROC曲线分析，确定M2BP诊断不同肝纤维化分级的最佳诊断阈值，并计算曲线下面积（area under the curve，AUC）以评估诊断效能。根据不同血吸虫病肝纤维化分级所对应的M2BP最佳诊断阈值，分别预测各效能评估组血清样本的肝纤维化分级，并与B超检查结果进行符合率比较和Kappa一致性检验。结果　根据B超检查结果，234份血清样本中血吸虫病肝纤维化0、Ⅰ、Ⅱ级和Ⅲ级样本分别为79、87、46、22份，不同肝纤维化分级样本血清M2BP平均浓度分别为（0.40 ± 0.31）［95%可信区间（confidence interval，CI）：（0.33，0.47）］、（0.64 ± 0.48）［95% CI：（0.53，0.74）］、（1.76 ± 0.58）［95% CI：（1.59，1.93）］ μg/mL和（2.56 ± 0.93）［95% CI：（2.14，2.97）］ μg/mL，差异有统计学意义（F = 150.796，P < 0.001），且血吸虫病肝纤维化严重程度与血清M2BP浓度呈正相关（rs = 0.715，P < 0.001）。血吸虫病肝纤维化0、Ⅰ、Ⅱ、Ⅲ级ROC曲线组和效能评估组样本分别为55份和24份、61份和26份、32份和14份、15份和7份，不同肝纤维化分级ROC曲线组和效能评估组血清M2BP浓度分别为（0.39 ± 0.29） μg/mL和（0.42 ± 0.36） μg/mL、（0.59 ± 0.47） μg/mL和（0.75 ± 0.51） μg/mL、（1.73 ± 0.59）μg/mL和（1.85 ± 0.57） μg/mL、（2.46 ± 0.64） μg/mL和（2.76 ± 1.41） μg/mL，差异均无统计学意义（F = 0.196、1.967、0.417、0.491，P均> 0.05）。血清M2BP诊断血吸虫病肝纤维化的ROC曲线分析结果显示，其对肝纤维化Ⅰ、Ⅱ级和Ⅲ级的最佳诊断阈值分别为0.347 86（AUC = 0.635，P < 0.05）、1.188 83 μg/mL（AUC = 0.938，P < 0.000 1）和2.021 21 μg/mL（AUC = 0.821，P < 0.000 1）。诊断效能评估结果显示，M2BP最佳诊断阈值对血吸虫病肝纤维化Ⅰ级、Ⅱ级和Ⅲ级的预测结果与B超检查结果的符合率分别为69.23%、85.71%和71.43%，差异无统计学意义（[χ2] = 1.340，P > 0.05），总体一致性检验呈中等程度一致［Kappa = 0.608，95% CI：（0.428，0.788）；Z = 6.609，P < 0.000 1］。结论　血清M2BP可作为辅助诊断血吸虫病肝纤维化中、晚期的潜在生物标志物，但其对早期血吸虫病肝纤维化的诊断价值有限。

关键词: 血吸虫病, 肝纤维化, Mac?2结合蛋白, 阈值, 诊断效能

Abstract: Objective　To evaluate the value of serum Mac⁃2 binding protein (M2BP) for assessment of the severity of schistosomiasis⁃induced liver fibrosis, so as to provide insights into non⁃invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis. Methods　A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B⁃ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis⁃induced liver fibrosis groups) according to B⁃ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7 ∶ 3. Serum M2BP concentration was measured in four groups using the enzyme⁃linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis⁃induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group. Results　Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis⁃induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B⁃ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis⁃induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis⁃induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis⁃induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B⁃ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis⁃induceed liver fibrosis were 69.23%, 85.71% and 71.43% ([χ2] = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1]. Conclusions　Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis⁃induced liver fibrosis; however, its diagnostic value for early⁃stage schistosomiasis⁃induced liver fibrosis remains limited.

Key words: Schistosomiasis, Liver fibrosis, Mac?2 binding protein, Threshold, Diagnostic performance

中图分类号:

R532.21

吴俊, 罗美群, 谢曙英, 朱荣华, 徐慧, 汤龙, 胡飞, 丁晟. 血清Mac⁃2结合蛋白对血吸虫病肝纤维化严重程度的诊断价值[J]. 中国血吸虫病防治杂志（中英文）, 2026, 38(1): 38-43.

WU Jun, LUO Meiqun, XIE Shuying, ZHU Ronghua, XU Hui, TANG Long, HU Fei, DING Sheng. Diagnostic value of serum Mac⁃2 binding protein for the severity of schistosomiasis⁃induced liver fibrosis [J]. Chinese Journal of Schistosomiasis Control, 2026, 38(1): 38-43.

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血清Mac⁃2结合蛋白对血吸虫病肝纤维化严重程度的诊断价值

Diagnostic value of serum Mac⁃2 binding protein for the severity of schistosomiasis⁃induced liver fibrosis

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