声触诊弹性成像线性结合超声评分细分慢性乙肝患者肝纤维化程度

Sound touch elastography linear combined with ultrasound score for staging liver fibrosis in patients with chronic hepatitis B

目的研究声触诊弹性成像(STE)线性结合超声评分(US)分期诊断慢性乙型病毒性肝炎(CHB)肝纤维化的价值, 探讨二者结合能否提升细分CHB肝纤维化程度的诊断效能, 并与STE线性结合血清学模型比较, 以寻求最佳线性组合模型。方法纳入2018年9月至2021年12月于广东医科大学附属深圳市第三人民医院收集的313例研究对象, 包括已完成肝脏穿刺活检的CHB患者259例和54例健康志愿者。CHB患者按METAVIR分级标准入组为肝纤维化各组(F1~F4组), 健康志愿者作为对照组。所有受检者均接受肝脏超声、STE检查及肝功能血生化指标检测。依据肝脏超声进行US, STE测量肝硬度值(LSM), 依据血生化指标计算天冬氨酸转氨酶和血小板比率指数(APRI)。采用Fisher判别分析依次建立LSM与US的线性结合(LC)诊断模型、LSM与APRI的线性结合(LC2)诊断模型。采用Spearman秩相关分析US、LSM、APRI、LC2及LC与病理结果的相关性。绘制US、LSM、APRI、LC2及LC诊断CHB肝纤维化的ROC曲线, 根据准确性、敏感性、特异性及ROC曲线下面积(AUC)评估上述诊断指标的诊断效能。结果 US与LSM线性组合公式为LC=0.986 0×US+0.166 7×LSM, LC与病理结果呈高度正相关(r_(s)=0.851, P<0.001), 高于US、LSM、LC2 、APRI与病理结果的相关性(rs=0.825、0.775、0.802、0.586, 均P<0.001)。LC显示出最佳诊断效能, 诊断≥F1、≥F2、≥F3期肝纤维化及=F4期肝硬化的AUC分别为0.945、0.911、0.954、0.955, 优于US的AUC(0.913、0.879、0.934、0.916)、LSM的AUC(0.860、0.871、0.934、0.952)以及LC2的AUC(0.899、0.883、0.941、0.946)。与US相比, LC诊断≥F1、≥F2、≥F3期肝纤维化和=F4期肝硬化的AUC分别提高了3.2%、3.2%、2.0%和3.9%, 差异有统计学意义(均P<0.05);与LSM相比, LC的AUC分别提高8.5%、4.0%、2.0%和0.3%, 除=F4期肝硬化外, 差异有统计学意义(均P<0.05);与LC2相比, LC的AUC分别高4.6%、2.8%、1.3%和0.9%, 且诊断在≥F1、≥F2期肝纤维化时, 差异有统计学意义(均P<0.05);LC2总体效能较LSM无明显提高(P>0.05)。结论 US、LSM、LC2及LC均可应用于分期诊断CHB肝纤维化程度, LC诊断效能优于单独应用US、LSM、LC2, 特别在细分CHB肝纤维化程度方面表现优异, 是一种极具前景的无创性新型诊断指标。

Objective To study the value of sound touch elastography(STE)linear combined with ultrasound score(US)in the diagnosis of chronic hepatitis B(CHB)liver fibrosis,and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis.Furthermore,a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University,including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers.CHB patients were divided into liver fibrosis group(F1-F4 group)according to METAVIR classification standard,and healthy volunteers were used as the control group.All subjects underwent liver ultrasound examination,STE and blood biochemical indexes of liver function.The US was performed according to the liver ultrasound examination,and the liver stiffness measurement(LSM)was measured by STE,aspartate aminotransferase and platelet ratio index(APRI)was calculated by blood biochemical index.Fisher discriminant analysis was used to establish the linear combination(LC)diagnostic marker of US and LSM,and the linear combination(LC2)diagnostic marker of LSM and APRI,successively.Spearman rank correlation coefficient was used to analyze the correlations between US,LSM,APRI,LC2,LC and pathological results.The ROC curves of US,LSM,APRI,LC2 and LC for diagnosing CHB liver fibrosis were plotted,and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy,sensitivity,specificity and area under the ROC curve(AUC).Results The formula for the linear combination of US and LSM was LC=0.9860×US+0.1667×LSM,and LC was highly positively correlated with pathological findings(rs=0.851,P<0.001),higher than US,LSM,LC2 and APRI(r_(s)=0.825,0.775,0.802,0.586,all P<0.001).LC showed the best diagnostic efficiency.The AUCs for diagnosing≥F1,≥F2,≥F3 liver fibrosis and=F4 cirrhosis were 0.945,0.911,0.954,0.955,respectively,which superior to the AUCs of US(0.913,0.879,0.934 and 0.916,respectively),the AUCs of LSM(0.860,0.871,0.934 and 0.952,respectively)and the AUCs of LC2(0.899,0.883,0.941,0.946,respectively).Compared with US,the AUC of LC diagnosis of≥F1,≥F2,≥F3 liver fibrosis and=F4 cirrhosis increased by 3.2%,3.2%,2.0%and 3.9%,respectively,with all significant differences(P<0.05).Compared with LSM,the AUC of LC increased by 8.5%,4.0%,2.0%and 0.3%,respectively,with significant difference(P<0.05)except for stage=F4 cirrhosis.Compared with LC2,the AUC of LC increased by 4.6%,2.8%,1.3%and 0.9%,respectively,and there were significant differences in the diagnosis of≥F1 and≥F2 liver fibrosis(P<0.05).Moreover,the overall efficiency of LC2 was not significantly improved than LSM,the difference was not significant(P>0.05).Conclusions US,LSM,LC2 and LC can be used to diagnose the degree of CHB liver fibrosis,but LC is better than US or LSM and LC2 alone,especially in the subdivision of mild liver fibrosis,which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.