血清寡糖链检测对HBV相关肝细胞癌的诊断价值

Clinical value of serum Glycan-Test in the diagnosis of hepatitis B virus-related hepatocellular carcinoma

目的评价寡糖链检测(G-Test)试剂盒(荧光毛细管电泳法)辅助诊断HBV相关肝细胞癌(HCC)的临床价值。方法收集2017年8月-2018年6月就诊于北京佑安医院的患者血清样本310例,其中HBV相关HCC(HCC组)170例,乙型肝炎肝硬化(肝硬化组)50例,慢性乙型肝炎(肝炎组)85例,其他脏器恶性肿瘤(其他恶性肿瘤组)5例。检测血清寡糖链组分的相对浓度,计算并分析G-Test试剂盒在临床诊断中的灵敏度、特异度、总符合率和阳性预测值、阴性预测值,并与血清AFP进行方法学比较。非正态计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较使用Dunn’s多重比较,计数资料两组间比较采用χ2检验。利用受试者工作特征曲线(ROC曲线)对诊断效能进行分析,利用logistic回归建立G-Test与AFP联合诊断模型,受试者工作特征曲线下面积(AUC)的比较采用Z检验。结果HCC组患者G值[6.46(5.73~7.07)]明显高于肝炎组[3.38(2.85~4.18)]及肝硬化组[3.99(3.13~5.21)]患者(H值分别为107.9、104.2,P值均<0.001)。HCC组患者AFP的水平明显高于肝炎组患者[0.77(0.45~1.77)log10 ng/ml vs 0.58(0.41~0.89)log10 ng/ml,H=33.65,P=0.025]。G-Test的灵敏度83.53%,特异度为74.29%,总体符合率为79.36%,阳性预测值79.78%,阴性预测值78.79%。G-Test与AFP单独诊断的AUC分别为0.846与0.611,G-Test的AUC明显高于AFP(Z=5.795,P<0.001),G-Test联合AFP诊断的AUC为0.870,明显优于G-Test(Z=2.523,P=0.012)与AFP(Z=6.943,P<0.001)单独诊断效能。HCC早期与中晚期组间G-Test检出率均高于AFP>400 ng/ml检出率(χ2值分别为26.441、38.379,P值均<0.001)。AFP分别以<20、<200、<400 ng/ml为阴性临界值,G-Test在AFP阴性的HCC患者中检出率分别为86.24%、85.93%、85.31%。结论G-Test的灵敏度和特异度较好,具有辅助诊断HCC的临床应用价值,联合AFP诊断效能更好。

Objective To investigate the clinical value of the oligosaccharide chain detection kit Glycan-Test(G-Test,fluorescent capillary electrophoresis)in assisting the diagnosis of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods A total of 310 serum samples were collected from the patients who attended Beijing YouAn Hospital from August 2017 to June 2018,among which there were 170 samples of HBV-related HCC(HCC group),50 samples of hepatitis B cirrhosis(liver cirrhosis group),85 samples of chronic hepatitis B(hepatitis group),and 5 samples of other malignant tumors of visceral organs.The relative concentration of serum oligosaccharide chain was measured,and the sensitivity,specificity,overall coincidence rate,positive predictive value,and negative predictive value of G-Test in clinical diagnosis were calculated and analyzed.A methodological comparison was performed for G-Test and serum alpha-fetoprotein(AFP).The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups,and the Dunn’s multiple comparison test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between two groups.The receiver operating characteristic(ROC)curve was used to evaluate diagnostic efficiency,and the logistic regression model was used to establish a combined diagnostic model of G-Test and AFP.The Z test was used for comparsion of area under ROC curve.Results The HCC group had a significantly higher level of G-Test than the hepatitis group[6.46(5.73-7.07)vs 3.38(2.85-4.18),H=107.9,P<0.001]and the liver cirrhosis group[6.46(5.73-7.07)vs 3.99(3.13-5.21),H=104.2,P<0.001].The HCC group had a significantly higher AFP level than the hepatitis group[0.77(0.45-1.77)log10 ng/ml vs 0.58(0.41-0.89)log10 ng/ml,H=33.65,P=0.025].G-Test had a sensitivity of 83.53%,a specificity of 74.29%,an overall coincidence rate of 79.36%,a positive predictive value of 79.78%,and a negative predictive value of 78.79%.G-Test alone had a significantly larger AUC than AFP alone(0.846 vs 0.611,Z=5.795,P<0.001),and G-Test combined with AFP had an AUC of 0.870,which was significantly larger than that of G-Test alone(Z=2.523,P=0.012)or AFP alone(Z=6.943,P<0.001).There were significant differences in the detection rates of G-Test and AFP between the early-stage group and the advanced group(χ2=26.441、38.379,all P<0.001).At the negative cut-off values of<20,<200,and<400 ng/ml for AFP,G-Test had a detection rate of 86.24%,85.93%,and 85.31%,respectively,in HCC patients with negative AFP.Conclusion G-Test has good sensitivity and specificity and a certain clinical value in assisting the diagnosis of HCC,and G-Test combined with AFP has better diagnostic efficiency.