血清差异蛋白在慢性乙型肝炎肝纤维化中的诊断价值  

Clinical significance of serum differential protein examination in chronic hepatitis B related liver fibrosis

作　　者：李世波[1] 童永喜[2] 丁贤君[1] 林志益[1] 张浙恩 李绍佐[1] 

机构地区：[1]浙江省舟山医院感染科,316000 [2]浙江中医药大学附属第六人民医院

出　　处：《中华肝脏病杂志》2010年第12期881-885,共5页Chinese Journal of Hepatology

基　　金：基金项目：浙江省卫生厅A类课题（2006A118）

摘　　要：目的探讨慢性乙型肝炎肝纤维化患者血清差异蛋白质表达的临床意义，为肝纤维化的无创诊断提供依据。方法经肝活体组织检查证实为慢性乙型肝炎患者110例，建模组83例，验证组27例。肝纤维化按Ishak分期F≥3期为明显肝纤维化，建模组明显肝纤维化（F≥3）55例，无一轻度肝纤维化（F0～F2）28例，验证组明显肝纤维化15例，无一轻度肝纤维化12例。用基质辅助激光解析电离高分辨飞行时间串联质谱检测标本的血清蛋白质，得到每个样品的质谱图，应用FlexAnalsis3．0分析软件得到差异蛋白质图谱，并与临床病理诊断进行比较，建立遗传算法的诊断模型，并对模型的诊断效能进行验证。结桌明显肝纤维化组（F≥3）与无一轻度肝纤维化组（F0～F2）患者蛋白质图谱比较，得到差异有统计学意义（P〈0．01）的差异蛋白质15个，其中最显著的蛋白质为2081．73m／z和1944.41m／z，以这两个差异最显著的蛋白峰建立坐标系的样品分布，建立6个特征蛋白峰组成的遗传算法模型，采用该模型对12例无轻度肝纤维化组患者、15例明显肝纤维化组患者进行验证，结果识别率为100％，预测能力为94．14％，准确率为100％。结论检测血清差异蛋白质表达可早期判断患者肝纤维化的程度。Objective To investigate the clinical significance of the expression of serum differential protein in patients with chronic hepatitis B （CHB） related liver fibrosis. Methods One hundred and ten CHB patients confirmed by liver biopsies were enrolled, 83 for modeling and 27 for verification. According to Ishak staging, 55 patients in the modeling group were with significant liver fibrosis （F≥ 3） and 28 patients with normal/mild liver fibrosis （F0-F2）. While that in the verification group were 15 （F≥ 3） and 12 （F0-F2）, respectively. MALDI-TOF-MS/MS was used to detect serum proteins and the spectrum for each sample was analyzed in FlexAnalysis3.0 to produce the spectrum of differential proteins. The results were compared with clinicopathologic diagnosis and the diagnosis model based on genetic algorithm was established and evaluated. Results There were 15 proteins differentially expressed in significant liver fibrosis group and normal/mild fibrosis group （P 〈 0.01）, in which the differences on proteins 2081.73 m/z and 1944.41 m/z were the most significant. Based on these two proteins, the coordinate system was set up and the diagnosis model based on genetic algorithm was established by six characteristic peaks. After detecting 12 cases of normal/mild liver fibrosis and 15 cases of significant liver fibrosis, the results showed that the diagnostic model could identify significant fibrosis （F ≥ 3） and normal/mild liver fibrosis （F0-F2） at 100% recognition, 94.14% prediction and 100% accuracy. Conclusion Serum differential proteins examination can be used for early prediction of CHB related fibrosis. The study provides the basis for non-invasive diagnosis of hepatic fibrosis according to identifying the potential differences of the serum samples from patients with HBV related fibrosis.

关 键 词：肝硬化 肝炎 乙型 慢性 诊断 蛋白质组学 

分 类 号：R686[医药卫生—骨科学]