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Diagnostic Value of Abnormal Prothrombin in HBV-related AFP-negative Hepatocellular Carcinoma
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摘要:
目的 评估血清异常凝血酶原（DCP）对甲胎蛋白（AFP）阴性(AFP≤20 ng/mL）肝癌诊断价值及其水平与Child-Pugh分级、肿瘤大小、TNM分期、肿瘤分化程度的关系。 方法 回顾性纳入2016年6月−2017年12月在四川大学华西医院确诊为乙肝相关性肝病的住院患者459例，其中肝癌组136例，非肝癌组323例（肝硬化组173例，肝炎组150例）。所有患者血清AFP均≤20 ng/mL。用受试者工作特性 (ROC) 曲线分析血清DCP对AFP阴性肝癌的诊断效能，并分析血清DCP水平与肝癌临床特征间的关系。 结果 与非肝癌组相比，肝癌组男性的比例更高，年龄更大，血清DCP水平更高（中位数，22 mAU/mL vs.159 mAU/mL），差异均有统计学意义（P<0.001)。肝癌组与肝硬化组、肝炎组比较，三组患者在性别比、年龄、AFP、DCP水平等方面的差异均有统计学意义（P<0.001)。肝癌组的DCP水平高于肝硬化组（中位数，19 mAU/mL）和肝炎组（中位数，26 mAU/mL）（P<0.001)。在所有AFP阴性的患者中，以DCP诊断肝癌，其曲线下面积(AUC)为0.858，P<0.05。其诊断的最佳切点值为61 mAU/mL，对应的灵敏度为72.8%，特异度为88.2%，阳性预测值为61.1%，阴性预测值为89.7%。在不同大小肿瘤中，直径>3 cm者DCP水平高于直径≤3 cm者（P<0.05）。在不同TNM分期中，Ⅱ、Ⅲ期DCP水平高于Ⅰ期（P<0.05）。在不同Child-Pugh分级、不同分化程度的肝癌间DCP水平差异无统计学意义（P>0.05）。 结论 DCP对于AFP阴性肝癌有一定诊断价值，其水平升高可能与肝癌的进展相关。 Abstract:Objective To evaluate the diagnostic value of abnormal prothrombin (DCP) in Alpha-fetoproteins (AFP)-negative (AFP≤20 ng/mL) hepatocellular carcinoma and the relationship between DCP level and Child-Pugh grade, tumor size, TNM stage as well as differentiation. Methods The inpatients diagnosed with hepatitis B-related liver disease were collected from June 2016 to December 2017, The diagnostic efficacy of DCP for AFP-negative HCC was analyzed by ROC. Area under the curve (AUC), the best cut point, sensitivity, specificity, positive predictive value and negative predictive value were calculated. The relationship between DCP levels and the clinical characteristic of HCC was analyzed. Results A total of 459 hepatitis B markers positive patients were included, including 136 cases of hepatocellular carcinoma, 173 cases of hepatitis B cirrhosis and 150 cases of chronic hepatitis B. DCP in AFP-negative hepatocellular carcinoma group was significantly higher than that in non-HCC group (CHB and LC) (P<0.05). The AUC of DCP was 0.858, P<0.05. The optimal cut-off point for the diagnosis of hepatocellular carcinoma was 61 mAU/mL. The corresponding sensitivity, specificity, positive predictive value and negative predictive value were 72.8%, 88.2%, 61.1% and 89.7%, respectively. In different size of hepatocellular carcinoma, DCP level of those with diameter>3 cm was significantly higher than those with diameter≤3 cm (P<0.05). In different TNM stages, DCP level in stage Ⅱ and Ⅲ was significantly higher than that in stage Ⅰ (P<0.05). There was no significant difference of DCP level among different Child-Pugh grades and differentiation (P>0.05). Conclusion DCP has diagnostic value for AFP-negative hepatocellular carcinoma, its level may reflects the degree of tumor progression. -
Key words:
- Abnormal prothrombin /
- Alpha-fetoproteins /
- ROC curve /
- HBV /
- Hepatocelluler carcinoma
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图 1 肝癌组和非肝癌组患者血清DCP水平的比较
Figure 1. Comparision of DCP level in groups of HCC and non-HCC
图 2 肝癌组、肝硬化组、肝炎组患者血清DCP水平的比较
Figure 2. Comparision of DCP level in groups of HCC, LC and CHB
图 3 血清DCP水平在AFP阴性的患者中诊断肝癌的ROC曲线
Figure 3. Diagnosis of HCC in AFP-negative HCC patients by ROC curve of DCP
Arrow indicates the optimal cut-off value
图 4 肝癌患者不同Child-Pugh分级的DCP水平分布
Figure 4. DCP level in HCC stratified by Child-Pugh grade
图 5 肝癌患者不同TNM分期的DCP水平分布
Figure 5. DCP level in HCC stratified by TNM stage
* P<0.05, vs. Ⅰ
图 7 不同肝癌病灶直径中DCP水平分布
Figure 7. DCP level in HCC stratified by tumor diameter
* P<0.05，vs. >3 cm
表 1 研究患者的基线特征和观察指标
Table 1. Baseline characteristics of the study population
Characteristic HCC group (n=136) Non-HCC group P Total (n=223) LC (n=173) CHB (n=150) P1 P2 Male/female (case) 125︰11 150︰73# 130︰43# 120︰30# <0.001 <0.001 Age*/yr. 53 (46-62), 25-86 44 (36-52), 16-77# 49 (42-55), 23-77# 37 (30-46), 18-77# <0.001 <0.001 AFP*/(ng/mL) 5 (3-10), 0.63-19.54 5 (3-18), 1-1 210 4 (3-8), 0.61-19.45 18 (4-138), 1.15-1 210△ 0.084 <0.001 DCP*/(mAU/mL) 159 (47-1 059), 11-75 000 22 (16-34), 3-20 298# 19 (13-27), 3-1 837# 26 (19-38), 10-20 298# <0.001 <0.001 HCC: Hepatic cellular cancer; LC: Liver cirrhosis; CHB: Chronic hepatitis; *Median (P25-P75) , Min-Max; P1：Comparison between HCC and non-HCC groups; P2: Comparison between HCC, LC and CHB groups; #P<0.05, vs. HCC group; △P<0.05, vs. HCC and LC groups 
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