血浆支架蛋白SEC16A评估乙型肝炎相关肝硬化及肝细胞癌的临床价值

Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma

目的探明血浆支架蛋白SEC16A水平及相关模型诊断乙型肝炎病毒相关肝硬化(HBV-LC)及肝细胞癌(HBV-HCC)的临床价值。方法选择2017年6月至2021年10月河北医科大学第三医院经临床、实验室检查、影像学及肝组织病理学诊断的HBV-LC及HBV-HCC患者,设立健康对照组。血浆SEC16A水平采用酶联免疫吸附试验(ELISA)检测,血清甲胎蛋白(AFP)采用电化学发光仪检测。应用SPSS 26.0、MedCalc 15.0统计学软件分析血浆SEC16A水平与肝硬化、肝细胞癌发生和发展的关系,有序logistic回归模型分析相关因素,并建立SEC16A联合诊断模型(SAA),受试者操作特征曲线评估该模型诊断肝硬化及肝细胞癌的临床效能。Pearson相关性分析明确新型诊断标志物的影响因素。结果共纳入健康对照60例、HBV-LC 60例、HBV-HCC 52例,血浆SEC16A平均水平依次为(7.41±1.66)ng/ml、(10.26±1.86)ng/ml、(12.79±1.49)ng/ml,P<0.001;SEC16A诊断肝硬化、肝细胞癌灵敏度为69.44%、71.05%,特异度为89.36%、88.89%。SEC16A、年龄、AFP为HBV-LC、肝细胞癌发生的独立危险因素,以此建立模型SAA诊断界值分别为26.21、31.46,灵敏度为77.78%和81.58%,特异度为87.23%和97.22%;诊断早期HBV-HCC灵敏度、特异度分别为80.95%、97.22%。Pearson相关性分析显示:AFP水平与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、γ-谷氨酰转移酶(GGT)均呈正相关,P值均<0.01;而血清SEC16A水平仅在肝硬化组中与ALT、AST呈轻度正相关(r值分别为0.268、0.260,P值均<0.05)。结论血浆SEC16A可作为乙型肝炎肝硬化及肝细胞癌的诊断标志物,SEC16A联合年龄、AFP诊断模型SAA可显著提高HBV-LC及HBV-HCC的早期诊断率,其应用有助于HBV相关系列疾病进展的诊断及鉴别诊断。

Objective To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis(HBV-LC)and hepatocellular carcinoma(HBV-HCC).Methods Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical,laboratory examination,imaging,and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected.Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay(ELISA).Serum alpha-fetoprotein(AFP)was detected using an electrochemiluminescence instrument.SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer.A sequential logistic regression model was used to analyze relevant factors.SEC16A was established through a joint diagnostic model.Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis.Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers.Results A total of 60 cases of healthy controls,60 cases of HBV-LC,and 52 cases of HBV-HCC were included.The average levels of plasma SEC16A were(7.41±1.66)ng/ml,(10.26±1.86)ng/ml,(12.79±1.49)ng/ml,respectively,with P<0.001.The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44%and 71.05%,and 89.36%and 88.89%,respectively.SEC16A,age,and AFP were independent risk factors for the occurrence of HBV-LC and HCC.SAA diagnostic cut-off values,sensitivity,and specificity were 26.21 and 31.46,77.78%and 81.58%,and 87.23%and 97.22%,respectively.The sensitivity and specificity for HBV-HCC early diagnosis were 80.95%and 97.22%,respectively.Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),andγ-glutamyltransferase(GGT)with P<0.01,while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group(r=0.268 and 0.260,respectively,P<0.05).Conclusion Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma.SEC16A,combined with age and the AFP diagnostic model with SAA,can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis.Additionally,its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.