甲胎蛋白和甲胎蛋白异质体比率(AFP-L3%)对HBV相关早期肝细胞癌的诊断效能分析

Diagnostic efficacy of alpha-fetoprotein and alpha-fetoprotein L3%in hepatitis B virus-related early-stage hepatocellular carcinoma

目的探讨甲胎蛋白(AFP)、AFP异质体L3(AFP-L3)在HBV相关早期肝细胞癌(HCC)中的诊断效能及最佳截断值。方法纳入2019年1月—2022年7月在中山大学附属第三医院就诊的首次诊断且尚未治疗的HBV相关HCC患者(HCC组)共1080例(其中中国肝癌分期Ⅰa~Ⅱa期肝癌620例),346例慢性乙型肝炎患者(CHB组)和293例HBV相关肝硬化患者(LC组)为对照组,分析AFP和AFP-L3%筛查HBV相关早期HCC的诊断效能,包括灵敏度、特异度、受试者工作特征曲线下面积(AUC)等。偏态分布的计量资料两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni法。结果HCC组AFP、AFP-L3%水平显著高于CHB组和LC组(H分别为542.479、418.974,P值均<0.001)。在早期HCC中,AFP和AFP-L3%最佳截断值分别为8.7 ng/mL和5%,AFP单用时AUC最高,为0.816,灵敏度和特异度分别为66.9%、85.1%;联合使用AFP-L3%与单用AFP的AUC无明显差异(Z=0.609,P=0.543),但均显著高于单用AFP-L3%(AFP vs AFP-L3%:Z=8.173,P<0.001;AFP+AFP-L3%vs AFPL3%:Z=8.802,P<0.001)。结论AFP对HBV相关早期HCC有较好的诊断价值,并且优于AFP-L3%,为了提高早期HCC的检出率,应该下调AFP的筛查截断值。

Objective To investigate the diagnostic efficacy and optimal cut-off values of alpha-fetoprotein(AFP)and alphafetoprotein variant L3(AFP-L3)in hepatitis B virus(HBV)-related early-stage hepatocellular carcinoma(HCC).Methods A total of 1080 patients with HBV-related HCC(HBV-HCC)who were diagnosed for the first time and not yet treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2019 to July 2022 were enrolled as HCC group in the study,among whom there were 620 patients with CNLCⅠa-Ⅱa HCC,and in addition,346 patients with HBV-related chronic hepatitis B(CHB group)and 293 patients with HBV-related liver cirrhosis(LC group)were enrolled as controls.The diagnostic efficacy of AFP and AFP-L3%in screening for HBV-related early-stage HCC was analyzed,including sensitivity,specificity,and the area under the ROC curve(AUC).The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups;the Kruskal-Wallis H test was used for comparison between multiple groups,and the Bonferroni method was used for further comparison between two groups.Results The HCC group had significantly higher levels of AFP and AFP-L3%than the CHB group and the LC group(H=542.479 and 418.974,both P<0.001).In early-stage HCC,AFP and AFP-L3%had an optimal cut-off value of 8.7 ng/mL and 5%,respectively,and AFP alone had the largest AUC of 0.816,with a sensitivity of 66.9%and a specificity of 85.1%.There was no significant difference in AUC between AFP-L3%+AFP and AFP alone(Z=0.609,P=0.543),but both AFP-L3%+AFP and AFP alone had a significantly larger AUC than AFP-L3%alone(AFP vs AFP-L3%:Z=8.173,P<0.001;AFP+AFP-L3%vs AFP-L3%:Z=8.802,P<0.001).Conclusion AFP has a good value and is superior to AFP-L3%in the diagnosis of HBV-related early-stage HCC,and the screening cut-off value of AFP should be lowered in order to improve the detection rate of early-stage HCC.