FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较

目的评价FibroScan、GPR、APRI、NFS、FIB-4单独应用及FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者进展期肝纤维化的诊断价值。方法选取2014年11月-2018年8月在四川省人民医院行肝穿刺病理检查并确诊为CHB合并NAFLD的患者92例。根据肝穿刺病理SAF分级诊断标准,分为轻中度肝纤维化(F1+F2)组(n=69)和进展期肝纤维化(F3)组(n=23)。同时应用FibroScan测得肝脏硬度值,根据临床指标分别计算GPR、APRI、NFS、FIB-4。计量资料两组间比较采用Mann-Whitney U检验;相关性分析采用Spearman秩相关;多因素二元logistic回归构建联合预测因子(向前逐步回归法),绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并采用Delong方法进行比较,评价各种无创诊断方法单独及联合应用对CHB合并NAFLD进展期肝纤维化的诊断价值。结果轻中度肝纤维化组的FibroScan、GPR、APRI、NFS及FIB-4水平明显低于进展期肝纤维化组(Z值分别为-4.910、-3.425、-3.837、-3.873、-3.990,P值均<0.05)。相关性分析结果显示,FibroScan、GPR、APRI、NFS、FIB-4与肝纤维化病理分期均呈正相关(r值分别为0.518、0.361、0.405、0.407、0.418,P值均<0.001)。FibroScan、GPR、APRI、NFS及FIB-4单独应用对诊断进展期肝纤维化均有一定价值(AUC分别为0.844、0.740、0.770、0.771、0.779,P值均<0.001),但FibroScan诊断价值并不优于GPR、APRI、NFS、FIB-4(P值均>0.05)。将FibroScan分别与GPR、APRI、NFS、FIB-4联合,诊断进展期肝纤维化的AUC均较单独应用时明显提高(Z值分别为1.977、2.076、2.361、2.206,P值均<0.05);将FibroScan与GPR+APRI+NFS+FIB-4同时联合诊断进展期肝纤维化的AUC及95%可信区间为0.896(0.813~0.950)。结论FibroScan、GPR、APRI、NFS及FIB-4诊断进展期肝纤维化均有一定的临床价值,FibroScan分别与GPR、APRI、NFS、FIB-4联合诊断进展期肝纤维化的效能优于单项血清学模型,其中FibroScan联合NFS或FIB-4的临床价值可能最佳。

Value of Fibroscan combined with GPR,APRI,NFS or FIB-4 for progressive liver fibrosis in patients with chronic hepatitis B and nonalcoholic fatty liver disease

Objective To investigate the diagnostic value of FibroScan,gamma-glutamyl transpeptidase-to-platelet ratio(GPR),aspartate aminotransferase-to-platelet ratio index(APRI),nonalcoholic fatty liver disease(NAFLD)fibrosis score(NFS),and fibrosis-4(FIB-4)used alone or FibroScan combined with GPR,APRI,NFS,or FIB-4 for progressive liver fibrosis in patients with chronic hepatitis B(CHB)and NAFLD.Methods A total of 92 patients who underwent liver biopsy in Sichuan Provincial People’s Hospital from November 2014 to August 2018 and were diagnosed with CHB and NAFLD were enrolled.Based on the SAF scoring system for liver biopsy,these patients were divided into mild-to-moderate liver fibrosis(F1+F2)group with 69 patients and progressive liver fibrosis(F3)group with 23 patients.FibroScan was used to obtain liver stiffness measurement(LSM),and GPR,APRI,NFS,and FIB-4 were calculated based on clinical indices.The Mann-Whitney U test was used for comparison of continuous data between two groups.Spearman rank correlation was used for correlation analysis.A multivariate binary logistic regression analysis(forward stepwise regression)was used to construct combined predictive factors.The receiver operating characteristic(ROC)curve was plotted,and the area under the ROC curve(AUC)was calculated,and Delong method was used to compare the AUC to evaluate the early-warning value of each noninvasive diagnostic method used alone or in combination in the diagnosis of CHB and progressive liver fibrosis.Results The mild-to-moderate liver fibrosis group had significantly lower values of FibroScan,GPR,APRI,NFS,and FIB-4 than the progressive liver fibrosis group(Z=-4.910,-3.425,-3.837,-3.873,and-3.990,all P<0.05).The correlation analysis showed that FibroScan,GPR,APRI,NFS,and FIB-4 were positively correlated with the pathological staging of liver fibrosis(r=0.518,0.361,0.405,0.407,and 0.418,P<0.05).FibroScan,GPR,APRI,NFS,and FIB-4 used alone had a certain clinical value in the diagnosis of progressive liver fibrosis(AUC=0.844,0.740,0.770,0.771,and 0.779,all P<0.001),while FibroScan was not superior to GPR,APRI,NFS,and FIB-4(P>0.05).FibroScan combined with GPR,APRI,NFS,or FIB-4 had a significantly higher AUC than GPR,APRI,NFS,or FIB-4 used alone in the diagnosis of progressive liver fibrosis(Z=1.977,2.076,2.361,and 2.206,all P<0.05).FibroScan combined with these four indices had an AUC of 0.896(95%confidence interval:0.813-0.950).Conclusion FibroScan,GPR,APRI,NFS,and FIB-4 have a certain clinical value in the diagnosis of progressive liver fibrosis,and FibroScan combined with GPR,APRI,NFS,or FIB-4 has higher efficiency than GPR,APRI,NFS,or FIB-4 used alone in the diagnosis of progressive liver fibrosis,among which FibroScan combined with NFS or FIB-4 may have the best clinical value.