血清甲胎蛋白异质体在慢性肝病中的表达及对肝癌的诊断价值探讨

Expression of serum alpha fetoprotein heterogeneity in chronic liver disease and its diagnostic value for hepatocellular carcinoma

目的探讨血清甲胎蛋白异质体(AFP-L3)在慢性肝病中的表达及对肝癌的诊断价值。方法选取2013年10月至2019年3月在中国科学院大学宁波华美医院住院治疗的肝病患者341例,包括慢性肝炎88例、肝硬化97例、肝癌145例(初发60例、复发39例、经导管动脉化疗栓塞术治疗后23例、手术和射频治疗后23例)、慢加急性肝衰竭11例,比较不同组别患者之间AFP和AFP-L3(%)水平的差异,绘制受试者工作曲线(ROC)分析AFP-L3(%)对肝癌的诊断效能。结果肝炎、肝硬化、慢加急性肝衰竭、肝癌(初发)患者血清AFP-L3(%)和AFP的总体差异均有统计学意义(Hc=28.384、9.913,P=0.001、0.019);两两比较显示肝癌(初发)患者血清AFP-L3(%)水平均高于肝炎、肝硬化患者(P均<0.05),血清AFP水平高于肝硬化患者(P<0.05),但AFP-L3(%)和AFP与慢加急性肝衰竭患者均差异不大(P均>0.05)。肝癌复发患者AFP-L3(%)和AFP水平均显著高于肝癌手术和射频治疗者(P均<0.05)。肿瘤大小、TNM分期影响血清AFP水平(P均<0.05),但病因、肿瘤大小和数量、癌栓、CTP评分和TNM分期等多种病理因素均不影响血清AFP-L3(%)水平。血清AFP-L3(%)对肝癌的鉴别诊断价值优于AFP(Z=2.637,P=0.008);AFP-L3诊断肝癌的最佳截断值为6.10%,特异性和敏感性分别为76.63%、61.29%。结论血清AFP异质体对肝癌的诊断价值优于AFP,其受病理因素的影响较小。为提高诊断效率,可通过大样本的验证建立可靠的Cut-off值。

Objective To investigate the expression of alpha fetoprotein(AFP)-L3 in chronic liver disease and its diagnostic value for hepatocellular carcinoma.Methods From October 2013 to March 2019,341 patients with liver diseases in Huamei Hospital,University of Chinese Academy of Sciences were selected,including 88 cases of chronic hepatitis,97 cases of cirrhosis,145 cases of hepatocellular carcinoma(60 cases of initial onset,39 cases of recurrence,23 cases treated by transcatheter arterial chemoembolization,23 cases treated by surgery and radiofrequency therapy)and 11 cases with acute-on-chronic liver failure.The difference of AFP and AFP-L3(%)levels between different groups was compared.The diagnostic efficacy of AFP-L3(%)for hepatocellular carcinoma was analyzed by using receiver operating curve(ROC).Results There were significant differences in serum AFP-L3(%)and AFP between patients with hepatitis,cirrhosis,acute-on-chronic liver failure and hepatocellular carcinoma(initial onset)(Hc=28.384,9.913,P=0.001,0.019).Post hoc multiple comparisons showed that the serum AFP-L3(%)levels of patients with hepatocellular carcinoma(initial onset)were higher than those of patients with hepatitis and cirrhosis(all P<0.05).The level of serum AFP in patients with hepatocellular carcinoma(initial onset)was higher than that of patients with cirrhosis(P<0.05),but there was no significant difference between patients with hepatocellular carcinoma(initial onset)and patients with acute-on-chronic liver failure for AFP-L3(%)and AFP(all P>0.05).The levels of AFP-L3(%)and AFP in patients with recurrence of hepatocellular carcinoma were significantly higher than those in patients undergoing hepatocellular carcinoma surgery and radiofrequency therapy(P<0.05).Tumor size and TNM stage affected serum AFP level(all P<0.05),but etiology,tumor size and number,tumor thrombus,CTP score and TNM stage had little relationship with serum AFP-L3(%)(all P>0.05).The diagnostic value of serum AFP-L3(%)was better than that of AFP(Z=2.637,P=0.008);the best cut-off value of AFP-L3 in the diagnosis of hepatocellular carcinoma was 6.10%,and the specificity and sensitivity were 76.63%and 61.29%,respectively.Conclusions The diagnostic value of serum alpha-fetoprotein heterogeneity in hepatocellular carcinoma is better than that of AFP,which is less affected by pathological factors.In order to improve the diagnostic efficiency,we can establish reliable cut-off value by validating large samples in the laboratory.