基于血清高尔基体蛋白73的代偿期乙型肝炎肝硬化无创诊断模型的建立及初步应用

Establishment and preliminary application of serum Golgi protein 73 based noninvasive diagnostic model for compensated stage hepatitis B cirrhosis

目的在进一步探究血清高尔基体蛋白(GP)73对代偿期乙型肝炎肝硬化的诊断价值的基础上,构建基于血清GP73和其他常规血清学指标的代偿期乙型肝炎肝硬化诊断模型并评估其诊断效能和适用性。方法选择2010年1月至2017年12月在解放军总医院第五医学中心就诊的666例慢性乙型肝炎患者为研究对象,并根据诊断代偿期肝硬化是否依据肝脏组织学检查分为临床诊断组和病理诊断组。在临床诊断组中建立代偿期乙型肝炎肝硬化诊断模型,并与目前临床使用的肝硬化诊断模型天冬氨酸转氨酶/血小板比值指数(APRI)、FIB-4指数和肝脏硬度测量值(LSM)进行比较。最后用病理诊断组对该诊断模型进一步验证。结果在临床诊断组中,GP73与APRI、FIB-4、LSM诊断肝硬化受试者工作特征曲线下面积(AUC)分别为0.842、0.857、0.864和0.832,四项指标诊断效能相当(P值均>0.05)。进而通过logistic回归分析,建立了代偿期乙型肝炎肝硬化诊断模型(GAPA):logitP=1/[1+exp(1.614-0.054×GP73-0.045×Age+0.030×PLT-0.015×ALP)]。该模型的AUC高达0.940,最佳截点值为0.41,对应的诊断灵敏度和特异度分别为0.92和0.82,诊断效能优于APRI、FIB-4、LSM以及GP73单用(P值均<0.05)。在病理诊断组,GAPA的AUC为0.877,与LSM(0.891)和FIB-4(0.847)的诊断效能相当(P值均>0.1),但仍优于APRI(0.811)和GP73单用(0.780)(P值均<0.001)。结论研究中建立的代偿期乙型肝炎肝硬化诊断模型GAPA在临床诊断组和病理诊断组都有较好的诊断效能,对资源相对匮乏或未开展LSM地区的慢性乙型肝炎患者代偿期肝硬化有一定的辅助诊断价值。

Objective To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein(GP)73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis.Methods 666 cases with chronic hepatitis B(CHB)who had visited to the Fifth Medical Center of People’s Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects,and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed.A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established.The current clinically used diagnostic model of liver cirrhosis,aspartate aminotransferase/platelet ratio index(APRI),fibrosis index(FIB)-4 and liver stiffness measurement(LSM)were compared.Eventually,the diagnostic model was verified step by step by pathological diagnosis group.Results The area under the receiver operating characteristic curve(AUC)of GP73 and APRI,FIB-4,and LSM for cirrhosis patients in the clinical diagnosis group were 0.842,0.857,0.864,and 0.832,respectively.The diagnostic efficiency of the four indicators were of similar(P value>0.05).A diagnostic model of compensated stage hepatitis B cirrhosis(GAPA)using logistic regression analysis was established:LogitP=1/[1+exp(1.614-0.054×GP73-0.045×Age+0.030×PLT-0.015×ALP)].The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41.The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82,respectively.The diagnostic efficiency was better than that of APRI,FIB-4,LSM and GP73 alone(P<0.05).The AUC of GAPA was 0.877 in the pathological diagnosis group,which was similar to the diagnostic efficacy of LSM(0.891)and FIB-4(0.847)(P>0.1),but still superior to that of APRI(0.811)and GP73 alone(0.780)(P<0.001).Conclusion GAPA,a diagnostic model for compensated stage hepatitis B cirrhosis established in this study,has a good diagnostic efficacy in both the clinical and pathological diagnosis group,and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.