摘要目的 探讨肝脏硬度值(liver stiffness measurement,LSM)和血清标志物用于评估ALT≤2×正常值上限(upper limit of normal value,ULN)的CHB患者肝纤维化程度的临床应用价值.方法 收集2015年10月至2017年12月在上海市(复旦大学附属)公共卫生临床中心肝胆内科就诊的ALT≤2×ULN的CHB患者284例,患者肝脏活组织检查前一天或当天行FibroScan检查,以及血常规、肝脏生物化学指标和血清纤维化指标检测,依据Scheuer方法进行肝组织病理学评价,并计算AST与血小板比值指数(AST to platelet ratio index,APRI)和FIB-4值.以肝组织病理结果为标准,比较LSM值与APRI和FIB-4值诊断肝纤维化分期的受试者工作特征(receiver operating characteristic curve,ROC)曲线及其曲线下面积(area under ROC,AUC).非正态分布数据以M(QR)表示,应用Kruskal-Wallis检验;两变量间相关性应用Spearman相关分析.结果 284例CHB患者中,男175例,女109例.炎症分级G1级175例、G2级88例、G3级21例,纤维化分期S1期153例、S2期53例、S3期34例、S4期44例.Spearman相关分析结果显示,LSM、APRI和FIB-4值均与肝纤维化分期均呈正相关(r值分别为0.650、0.484和0.317,均P<0.01).LSM诊断肝纤维化分期≥S2、≥S3、S4期的AUC分别为0.840、0.902和0.942;临界值分别为6.10、8.40和10.10 kPa.APRI和FIB-4值诊断肝纤维化分期≥S2期的AUC分别为0.755和0.638;诊断≥S3期的AUC分别为0.737和0.657;诊断S4期的AUC分别为0.804和0.694.在≤1×ULN、>1～≤2×ULN组LSM诊断≥S2期的AUC分别为0.857和0.813,临界值分别为5.90和7.80kPa;诊断≥S3期的AUC分别为0.890和0.892,临界值分别为8.10和9.50 kPa;诊断S4期的AUC分别为0.925和0.908,临界值分别为8.40和10.40 kPa.结论 LSM能准确地评估ALT≤2×ULN的CHB患者的肝纤维化分期,其临床应用价值优于血清标志物.

abstractsObjective To assess the diagnostic performance of liver stiffness measurement(LSM)and serum markers on hepatic fibrosis in chronic hepatitis B(CHB)patients with alanine aminotransferase(ALT)less than or equal to two times the upper limit of normal(≤2×ULN).Methods A total of 284 CHB patients with ALT≤2×ULN who were treated in Department of Hepatobiliary Medicine,Public Health Clinical Center,Shanghai from October 2015 to December 2017 were analyzed.FibroScan,routine blood tests and serum fibrosis markers were conducted on the day or one day before liver biopsy.The Scheuer scoring system was used for liver histologic assessment.Aspartate aminotransferase to platelet ration index(APRI)and FIB-4 were calculated.Based on the results of liver pathology,the area under receiver operating characteristic curve(AUROC)was used to evaluate the value of LSM and serum markers in the diagnosis of liver fibrosis stage.Non-normal distribution variables were expressed as M(QR)as appropriate,and compared by analysis of Kruskal-Wallis test as appropriate.The correlation between two variables was analyzed by Spearman correlation analysis.Results Of 284 CHB patients,175 were male and 109 were female.For inflammatory grading,175 cases were G1 grade,88 cases were G2,and 21 cases were G3.For fibrosis grading,153 cases were S1,53 cases were S2,34 cases were S3,and 44 cases were S4.Spearman correlation analysis showed that LSM,APRI and FIB-4 were positively correlated with hepatic fibrosis stage(r=0.650,0.484,and 0.317,respectively,all P<0.01).The AUC of LSM for predicting fibrosis≥S2,≥S3,and S4 were 0.840,0.902,and 0.942,respectively.The cut-off of LSM values were 6.10,8.40,and 10.10 kPa,respectively.The values of AUC of APRI and FIB-4 for predicting fibrosis≥S2 were 0.755 and 0.638,respectively,those for predicting fibrosis≥S3 were 0.737 and 0.657,respectively,and those for S4 were 0.804 and 0.694,respectively.The AUCs of LSM for predicting fibrosis≥S2 in patients with ALT≤1×ULN and those with ALT>1 -≤2×ULN were 0.857 and 0.813,respectively,those for fibrosis≥S3 were 0.890 and 0.892,respectively,and those for S4 were 0.925 and 0.908,respectively.The cut-off of LSM were 5.90 and 7.80 kPa,8.10 and 9.50 kPa,8.40 and 10.40 kPa,respectively.Conclusions LSM could accurately assess the degree of liver fibrosis in CHB patients with ALT≤2×ULN,which is superior to serum markers for predicting liver fibrosis stage.