寡糖链、甲胎蛋白对乙型肝炎病毒相关肝细胞癌风险筛查与诊断价值研究

Study on the Value of Oligosaccharide Chain and Alpha-fetoprotein for Risk Screening and Diagnosis of Hepatitis B Virus-related Hepatocellular Carcinoma

背景 肝细胞癌(HCC)是原发性肝癌(PLC)的主要病理分型,与乙型肝炎病毒(HBV)感染密切相关,HCC早期无明显症状,发现时多进展至中晚期阶段,有肝内、门静脉或其他部位转移,预后较差。在疾病早期对高风险人群进行定期筛查及早期诊断,对临床治疗及预后有重大意义。目的 探究寡糖链和甲胎蛋白(AFP)在HBV相关HCC的风险人群及患者中的应用价值,为临床诊断提供参考。方法 纳入2022年1—11月就诊于苏州大学附属第一医院的慢性HBV感染患者165例为研究对象,其中非HCC患者123例,HCC患者42例。通过电子病历系统收集患者一般资料(年龄、性别、肝硬化情况)、实验室检查指标[总胆红素(TB)、白蛋白(ALB)、血小板计数(PLT)、AFP],计算慢性肝病患者肝癌风险预测模型评分(aMAP评分),收集寡糖链标志物检测结果(G-Test)。将HCC患者作为HCC组(42例),非HCC患者根据aMAP评分进行分组,<50分为低风险组(40例)、50~60分为中风险组(44例)、>60分为高风险组(39例)。绘制受试者工作特征曲线(ROC曲线)分析AFP、G-Test及两者联合诊断HCC的效能,计算ROC曲线下面积(AUC),并用DeLong检验比较联合指标与单个指标AUC的差异。采用Kappa一致性检验分析AFP、G-Test与临床诊断结果的一致性。结果 HCC组患者AFP、G-Test高于低风险组、中风险组、高风险组,年龄、肝硬化比例高于低风险组、中风险组,ALB低于低风险组、中风险组,TB低于高风险组,PLT低于低风险组(P<0.05);高风险组患者年龄、TB、G-Test高于低风险组、中风险组,ALB、PLT低于低风险组、中风险组,肝硬化比例高于低风险组(P<0.05);中风险组患者的年龄、肝硬化比例高于低风险组,PLT低于低风险组(P<0.05)。AFP和G-Test诊断HCC的AUC分别为0.796(95%CI=0.706~0.886,P<0.001)、0.878(95%CI=0.813~0.943,P<0.001),两者联合诊断HCC的AUC为0.901(95%CI=0.844~0.957,P<0.001)。DeLong检验结果显示,联合诊断HCC的AUC高于AFP(Z=2.104,P=0.035)。一致性分析结果显示,AFP与临床诊断结果的一致率为84.8%(140/165),一致性中等(Kappa值=0.539,P<0.001),G-Test与临床诊断结果的一致率为89.5%(145/165),一致性较高(Kappa值=0.704,P<0.001)。G-Test诊断AFP阴性HCC的AUC为0.895(95%CI=0.839~0.952,P<0.001)。结论 寡糖链作为一种潜在血清生物标志物,对HBV相关HCC患者的诊断效能优于AFP,可作为AFP阴性HCC患者的补充检测标志物。

Background Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer(PLC)and is closely associated with Hepatitis B virus(HBV)infection.HCC in its early stages often presents no significant symptoms and is usually discovered at an advanced stage with liver,portal vein,or other site metastases,leading to a poor prognosis.Regular screening and early diagnosis in high-risk populations in the early stages of the disease are of great significance for clinical treatment and prognosis.Objective To explore the application value of oligosaccharides and alpha-fetoprotein(AFP)in the risk population and patients of HBV-related HCC,providing a reference for clinical diagnosis.Methods The study included 165 chronic HBV infection patients treated at the First Affiliated Hospital of Soochow University from January to November 2022,comprising 123 non-HCC and 42 HCC patients.Patient data(age,gender,cirrhosis status),laboratory indices[total bilirubin(TB),albumin(ALB),platelet count(PLT),AFP]were collected through electronic medical records,and a liver cancer risk prediction model score for chronic liver disease patients(aMAP score)was calculated,along with oligosaccharide marker test results(G-Test).HCC patients were classified as the HCC group(42 cases),and non-HCC patients were divided based on aMAP scores into low-risk(<50 points,40 cases),medium-risk(50-60 points,44 cases),and highrisk(>60 points,39 cases)groups.Receiver operating characteristic(ROC)curves were plotted to analyze the efficacy of AFP,G-Test,and their combined diagnosis of HCC,calculating the area under the ROC curve(AUC),and the DeLong test was used to compare the differences between combined and single indicator AUCs.Kappa consistency tests were used to analyze the consistency of AFP and G-Test with clinical diagnostic results.Results In patients with HCC,levels of AFP and G-Test were higher compared to those in the low-risk,medium-risk,and high-risk groups(P<0.05).Additionally,age and the proportion of liver cirrhosis were higher than those in the low-risk and medium-risk groups,ALB levels was lower than that of low risk group and medium risk group and TB levels were lower than those in the high-risk group,while PLT was lower than that in the low-risk group(P<0.05).In the high-risk group,patients exhibited higher age,TB,and G-Test levels compared to the low-risk and medium-risk groups,whereas ALB and PLT levels were lower than those in the low-risk and medium-risk groups,and the proportion of liver cirrhosis was higher than that in the low-risk group(P<0.05).Patients in the medium-risk group showed higher age and liver cirrhosis proportion compared to the low-risk group,and PLT was lower than that in the low-risk group(P<0.05).The AUCs for diagnosing HCC using AFP and G-Test were 0.796(95%CI=0.706-0.886,P<0.001)and 0.878(95%CI=0.813-0.943,P<0.001),respectively.The AUC for the combined diagnosis was 0.901(95%CI=0.844-0.957,P<0.001).DeLong test results showed that the AUC for combined diagnosis was higher than AFP alone(Z=2.104,P=0.035).Consistency analysis showed that the concordance rate of AFP with clinical diagnosis was 84.8%(140/165),with moderate consistency(Kappa=0.539,P<0.001),and for G-Test,it was 89.5%(145/165),indicating higher consistency(Kappa=0.704,P<0.001).The AUC of G-Test in diagnosing AFP-negative HCC was 0.895(95%CI=0.839-0.952,P<0.001).Conclusion Oligosaccharide chain markers can be used as a complementary detection marker for AFP-negative HCC patients as a potential serum biomarker with better diagnostic efficacy than AFP in patients with HBV-related HCC.