2023年 第26卷 第7期
《工程（英文）》 >> 2023年 第26卷 第7期 doi: 10.1016/j.eng.2023.03.008
血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的 临床意义
a Department of Microbiology & Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
b Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing 100034, China
c Sysdiagno (Nanjing)Biotechnology Company Limited, Nanjing 211800, China
# These authors contributed equally to this work.
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摘要
本研究的目的是探讨血清N-聚糖模型在285 例丙氨酸转移酶（alanine aminotransferase, ALT）水平正常（< 40 IU·L−1）的慢性乙型肝炎（慢性乙肝）患者中诊断显著肝纤维化和肝硬化的临床意义。对每位入组患者进行肝脏组织活检，并使用Ishak 评分系统评估患者肝脏组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱，每例患者的血清样本中共鉴定出9 个N-聚糖峰。利用机器学习算法，即随机森林（random forest, RF）构建更理想的血清N-聚糖模型，以诊断显著肝纤维化（≥ F3）和肝硬化（≥ F5），并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。肝脏组织活检结果显示，有显著肝纤维化和肝硬化的患者分别占63.86%（182/285）和16.49%（47/285），有显著炎症的患者为4.91%（14/285）。血清N-聚糖RF-A模型具有很好的诊断显著肝纤维化（≥ F3）的效能，其受试者工作特征曲线下面积（area under receiver operating characteristic curve, AUROC）为0.94，与肝脏组织活检的符合率为90.45%。在诊断肝硬化（≥ F5）时，血清N-聚糖RF-B模型的AUROC为0.97，与肝脏组织活检的符合率为88.94%。血清N-聚糖模型（RF-A 和RF-B）的诊断效能优于肝硬度值测量（liver stiffness measurement, LSM）、基于4 因子的纤维化指数（fibrosis index based on the four factors, FIB-4）和天冬氨酸转氨酶与血小板比率指数（aspartate aminotransferase-to-platelet ratio index, APRI）。在ALT 水平正常的慢性乙肝患者中，血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。
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