MRI与血清学定量指标检测对肝纤维化的诊断价值

Value of MRI and quantitative serological markers detection to the diagnosis of liver fibrosis

目的探讨MRI的信号强度值和化学发光法检测的4项血清学指标与肝纤维化分期的相关性,比较其对乙型病毒性肝炎肝纤维化无创诊断中的临床价值。方法 54例慢性乙型肝炎肝纤维化患者为观察组,12例体检健康者为对照组,分别行3.0T MRI扩散加权成像/磁敏感加权成像、造影剂增强后的T1加权序列检查,同时采用化学发光法检测血清透明质酸(hyaluronic acid,HA)、层黏连蛋白(laminin,LN)、三型前胶原N端肽(procollagen typeⅢN-terminal peptidase,PⅢNP)、Ⅳ型胶原(collagen typeⅣ,CⅣ)。以肝组织活检为诊断标准,分析扩散加权成像表观扩散系数(apparent diffusion coefficient,ADC)、磁敏感加权成像影像上相对增强(relative enhancement,RE)、肝脏-肌肉比率(liver/muscle ratio,LMR)值及4项血清学指标与肝纤维化分期的相关性;绘制ROC曲线,比较其用于诊断肝纤维化的临床价值;采用logistic逐步回归分析筛选出与诊断肝纤维化密切的指标,评价其联合检查的诊断价值。结果 2组ADC、RE、LMR以及血清HA、LN、PⅢNP、CⅣ水平比较差异均有统计学意义(P<0.05);ADC、RE及LMR与肝纤维化分期均呈负相关(r=-0.774、P<0.001,r=-0.663、P<0.001,r=-0.607、P<0.001),血清HA、LN、CⅣ及PⅢNP与肝纤维化分期呈正相关(r=0.678、P<0.001,r=0.729、P<0.001,r=0.804、P<0.001,r=0.587、P<0.001);观察组S0期ADC、RE及LN的AUC(0.697、0.576、0.447)与S1期(0.745、0.682、0.458)比较差异无统计学意义(P>0.05),S0、S1期LN的AUC值<0.5,S0、S1、S2期血清HA的AUC(0.576、0.583、0.756)、CⅣ的AUC(0.492、0.531、0.695)及PⅢNP的AUC(0.326、0.474、0.631)比较差异均无统计学意义(P>0.05),且PⅢNP在S0、S1期的AUC值<0.5,而LMR在S0、S1、S2、S3期的AUC差异均无统计学意义(P>0.05);逐步回归分析显示ADC、HA值与肝纤维化诊断密切相关(r=-7.734、P=0.022,r=0.046,P=0.033),ADC的AUC为0.89,其预测肝纤维化最佳临界值为ADC≤1.16×10-3 mm2/s,灵敏度为74.1%,特异度为91.7%;HA的AUC为0.87,其预测肝纤维化最佳临界值为HA≥102μg/L,灵敏度为68.5%,特异度为100.0%;ADC+HA联合的AUC为0.92,诊断肝纤维化的灵敏度为74.1%,特异度为100.0%;ADC+HA联合诊断乙型病毒性肝炎肝纤维化的AUC(0.92)、准确性(80.3%)、特异度(100.0%)均高于ADC、HA单项指标。结论随着肝纤维化程度加重,ADC、RE、LMR以及血清HA、LN、CⅣ和PⅢNP呈现不同变化,但诊断轻度肝纤维化的价值较低;ADC联合HA可提高乙型病毒性肝炎肝纤维化诊断的灵敏度和特异性。

Objective To investigate the relationship of the signal intensity of MRI and four serological markers detected by chemiluminescence immunoassay（CLIA）with the stages of liver fibrosis and to compare its clinical value to the diagnosis of hepatitis B-related liver fibrosis.Methods Fifty-four patients with chronic hepatitis B-related liver fibrosis（observation group）and 12 healthy volunteers（control group）underwent 3.0 T MRI DWI/magnetic susceptibility weighted imaging（SWI）and contrast enhanced T1-weighted sequencing,while the levels of serum hyaluronic acid（HA）,laminin（LN）,procollagen typeⅢ N-terminal peptide（PⅢNP）and typeⅣcollagen（CⅣ）were detected by CLIA.The result of liver biopsy was taken as the diagnostic criteria to analyze the correlations of DWI apparent diffusion coefficient（ADC）,SWI relative enhancement（RE）,liver/muscle ratio（LMR）and four serological markers with the stages of liver fibrosis.ROC was drawn to compare its diagnostic value to liver fibrosis.Logistic regression analysis was used to screen out the indicators closely related to the diagnosis of liver fibrosis and to assess the diagnostic value of joint detection.Results There were significant differences in ADC,RE,LMR,HA,LN,PⅢNP and CⅣ between two groups（P〈0.05）.ADC,RE and LMR were negatively correlated with the stage of liver fibrosis（r=-0.774,P〈0.001;r=-0.663,P〈0.001;r=-0.607,P〈0.001）,and HA,LN,CⅣ and PⅢNP were positively correlated with the stages of liver fibrosis（r=0.678,P〈0.001;r=0.729,P〈0.001;r=0.804,P〈0.001;r=0.587,P〈0.001）.There were no significant differences in the AUCvalues of ADC,RE and LMR between S0 stage（0.697,0.576,0.447）and S1 stage（0.745,0.682,0.458）（P〉0.05）,and the AUCvalue of LN in S0 and S1 stages were less than 0.5.Furthermore,there were no significant differences in the AUC values of HA（0.576,0.583,0.756）,CⅣ（0.492,0.531,0.695）and PⅢNP（0.326,0.474,0.631）among S0,S1 and S2 stages（P〉0.05）,and the AUCvalues of PⅢNP in S0 and S1 stages were less than 0.5.The AUCvalues of LMR showed no significant differences among S0,S1,S2 and S3 stages（P〉0.05）.The results of logistic regression analysis showed that ADC and HA were closely correlated with the diagnosis of liver fibrosis（r=-7.734,P=0.022;r=0.046,P=0.033）.When the cut-off value of ADC was≤1.16×10-3 mm2/s,the AUCfor predicting liver fibrosis was 0.89,the sensitivity was 74.1% and the specificity was 91.7%.When the cut-off value of HA was ≥102μg/L,the AUCfor predicting liver fibrosis was 0.87,the sensitivity was 68.5% and the specificity was 100.0%.The AUCof ADC＋HA was 0.92,the sensitivity was 74.1%and specificity was 100.0%.The AUC,accuracy（80.3%）and specificity of ADC＋HA were significantly higher than those of ADC or HA.Conclusion With the aggravation of liver fibrosis,ADC,RE,LMR,HA,LN,CⅣ and PⅢNP vary differently,but their diagnostic value on mild liver fibrosis is low.The joint detection of ADC and HA would improve the diagnostic sensitivity and specificity for hepatitis B-related liver fibrosis.