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[多种实验室血液学指标联合诊断甲胎蛋白阴性肝细胞癌的效能分析]

[Analysis of the diagnostic efficiency of combining multiple laboratory hematological indicators in alpha-fetoprotein-negative hepatocellular carcinoma].

作者信息

Wang H, Dong J, Bao J F, Wang C B, Lyu J X

机构信息

School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China.

Department of Clinical Laboratory Medicine, the First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2022 May 10;102(17):1303-1310. doi: 10.3760/cma.j.cn112137-20220115-00103.

Abstract

To establish a diagnostic model for alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) by combining multiple laboratory hematological indicators and explore its clinical diagnostic efficiency. A total of 124 inpatients, including 110 males and 14 females, aged 57 (51, 66) years, who were first diagnosed with AFP-NHCC in the PLA General Hospital were included from December 2011 to June 2017. Meanwhile, 331 cases of non-HCC were enrolled as the control group, including 279 males and 52 females, aged 58 (51, 63) years old, with 47 cases of hepatitis B virus (HBV) infection, 40 cases of liver cirrhosis, 64 cases of hepatic hemangioma or cysts, 7 cases of liver nodules, 8 cases of fatty liver, 146 cases of non-liver disease and 19 health controls. Subjects in the AFP-NHCC group and the control group were divided into a training group and a validation group. A total of 196 subjects were involved in the training group, including 103 AFP-NHCC patients and 93 non-HCC patients (19 healthy controls, 25 patients with HBV infection, 22 patients with liver cirrhosis, 23 patients with hepatic hemangioma or cyst, and 4 patients with liver nodules). The differences in laboratory parameters were analyzed, and a diagnostic model of AFP-NHCC under different AFP levels was established. Likewise, 259 subjects, including 113 patients with liver disease, were involved in the validation group to verify the diagnostic efficiency of the model for AFP-NHCC. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of different models, and the area under the curve (AUC) was calculated to evaluate the diagnostic performance of different models. In the training group, the indicators of AFP-NHCC diagnostic model included platelet (PLT), prothrombin activity (PTA), serum albumin (ALB), prothrombin time (PT) and carbohydrate antigen 19-9 (CA19-9), and the AUC of the model was 0.848 (95%: 0.786-0.911) when AFP≤5 μg/L. Similarly, the indicators of AFP-NHCC diagnostic model included PLT, PTA, ALB, PT and hematocrit (HCT), and the AUC of the model was 0.839 (95%: 0.780-0.897) when AFP≤10 μg/L. When AFP≤20 μg/L, the indicators of AFP-NHCC diagnostic model contained PLT, PTA, ALB, PT, HCT and AFP, and the AUC of the model was 0.866 (95%: 0.815-0.917). The AUC values of these three models were higher than those of AFP and CA19-9 alone for the diagnosis of AFP-NHCC [0.634 (95%: 0.560-0.709), 0.691 (95%:0.620-0.761), all <0.05]. The indicators screened by these three models were combined to establish the final diagnostic model, and the AUC of the model was 0.873 (95%: 0.824-0.923), with the sensitivity of 78.6% (81/103) and the specificity of 81.7% (76/93). In the validation group, the predictive AUC of the final model in liver disease patients was 0.892 (95%: 0.832-0.951), with the sensitivity of 100% (21/21) and the specificity of 71.7% (66/92), while in the total validation population, the predictive AUC was 0.931 (95%: 0.890-0.972), with the sensitivity of 100.0% (21/21) and the specificity of 75.6% (180/238). The final diagnostic model includes PLT, PTA, ALB, PT, HCT, CA19-9 and AFP, which has higher sensitivity and specificity, and has good diagnostic efficiency for the clinical diagnosis of AFP-NHCC.

摘要

通过结合多种实验室血液学指标建立甲胎蛋白阴性肝细胞癌(AFP-NHCC)的诊断模型,并探讨其临床诊断效率。选取2011年12月至2017年6月在解放军总医院首次诊断为AFP-NHCC的124例住院患者,其中男性110例,女性14例,年龄57(51,66)岁。同时,纳入331例非肝癌患者作为对照组,其中男性279例,女性52例,年龄58(51,63)岁,包括47例乙型肝炎病毒(HBV)感染、40例肝硬化、64例肝血管瘤或囊肿、7例肝结节、8例脂肪肝、146例非肝脏疾病及19例健康对照。将AFP-NHCC组和对照组患者分为训练组和验证组。训练组共196例受试者,包括103例AFP-NHCC患者和93例非肝癌患者(19例健康对照、25例HBV感染患者、22例肝硬化患者、23例肝血管瘤或囊肿患者及4例肝结节患者)。分析实验室参数差异,建立不同AFP水平下AFP-NHCC的诊断模型。同样,验证组纳入259例受试者,包括113例肝病患者,以验证该模型对AFP-NHCC的诊断效率。采用受试者工作特征(ROC)曲线分析不同模型的敏感性和特异性,并计算曲线下面积(AUC)以评估不同模型的诊断性能。在训练组中,AFP-NHCC诊断模型的指标包括血小板(PLT)、凝血酶原活动度(PTA)、血清白蛋白(ALB)、凝血酶原时间(PT)和糖类抗原19-9(CA19-9),当AFP≤5μg/L时,该模型的AUC为0.848(95%:0.786-0.911)。同样,当AFP≤10μg/L时,AFP-NHCC诊断模型的指标包括PLT、PTA、ALB、PT和血细胞比容(HCT),该模型的AUC为0.839(95%:0.780-0.897)。当AFP≤20μg/L时,AFP-NHCC诊断模型的指标包括PLT、PTA、ALB、PT、HCT和AFP,该模型的AUC为0.866(95%:0.815-0.917)。这三个模型的AUC值均高于单独使用AFP和CA19-9诊断AFP-NHCC的AUC值[0.634(95%:0.560-0.709),0.691(95%:0.620-0.761),均<0.05]。将这三个模型筛选出的指标合并建立最终诊断模型,该模型的AUC为0.873(95%:0.824-0.923),敏感性为78.6%(81/103),特异性为81.7%(76/93)。在验证组中,最终模型在肝病患者中的预测AUC为0.892(95%:0.832-0.951),敏感性为100%(21/21),特异性为71.7%(66/92),而在整个验证人群中,预测AUC为0.931(95%:0.890-0.972),敏感性为100.0%(21/21),特异性为75.6%(180/238)。最终诊断模型包括PLT、PTA、ALB、PT、HCT、CA19-9和AFP,具有较高的敏感性和特异性,对AFP-NHCC的临床诊断具有良好的诊断效率。

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