Real-time Shear Wave Elastography And Liver Fibrosis Serological Indexes In Evaluation Of Experimental Rabbit Liver Fibrosis

ObjectiveTo investigate the value of real-time shear wave elastography and serum fibrosis biomarkers in evaluating the degree of liver fibrosis in rabbits MethodsHealthy adult white rabbits were randomly divided into control group(8 rabbits)and an experimental group(40 rabbits).In the first two weeks,rabbits in the experimental group were subcutaneously injected 0.3ml/kg 50% CCL4-olive oil solution twice a week.From the 3rd week,the quantity was 0.2ml/kg,twice a week.Rabbits in the control group were subcutaneously injected 0.3ml/kg normal saline twice a week.From the 3rd week,the quantity was 0.2ml/kg,twice a week.Modeling process,eating,drinking,fur,activities and weight changes of rabbits were continuously observed.At 4,8,12 and 16 weeks after the experiment,eight rabbits in the experimental group and two rabbit in the control group,after fasting for 8 hours,were randomly selected to examine liver function(TIBL,IBIL,ALT,ALP,etc.)and serum fibrosis biomarkers(HA,PIIINP,CIV and LN)with 3ml arterial blood at marginal ears.The liver parenchymal echoes,liver capsule,gallbladder change and ascites were observed by two-dimensional ultrasonography and using SWE to measure the Emean value(KPa)of Young's modulus.Subsequently,the rabbits were killed and then tissues in the middle liver lobe were sent for HE,reticular fiber and Masson staining for pathological observation and hepatic fibrosis stages.Then an analysis was made to determine whether the Emean value and serum fibrosis biomarkers(HA,PIIINP,CIV,LN)were correlated with pathological stages of hepatic fibrosis and evaluate their diagnostic efficiency on the liver-fibrosis severities by using the receiver operating characteristic(ROC)curve.Results1.Rabbits in the control group maintained vigorous activities,healthy appetites and gained weight at the end of the experiment.According to the pathologic sample,the liver surface was smooth,soft and delicate,in normal size,looked kermesinus,with sharp edge and good elasticity.Pathology showed that the hepatic lobules were normal,and there was no fibrosis.Rabbits in the experimental group had poor appetites,looked dispirited,disliked exercising,maintained or lost weight at the end of the experiment.The weight of rabbits in the experimental group was much lower than that of the control group and the difference was statistically significant.2.According to the pathological stage of liver fibrosis in rabbits :In the S1,S2,S3 stage of rabbit hepatic fibrosis,two-dimensional ultrasonography showed only a homogeneous,thickening or slightly enhanced liver parenchymal echoes with liver surface that was still smooth.However,liver parenchymal echoes were thickening and uneven,with nodular echoes,in liver cirrhosis.3.In the S0,S1,S2,S3,S4 stage of rabbit hepatic fibrosis,the Emean value was respectively(7.05±0.54)KPa,(9.93±1.70)KPa,(15.27±3.71)KPa,(18.88±2.94)KPa and(23.51±1.38)KPa.The difference was statistically significant(F=74.238,P<0.01).Moreover,the difference in each stage was statistically significant(P=0.000).Although the overall distribution of HA,CIV and LN differs,the HA value was statistically significant only in the S0,S2 and S3 stage.The difference was statistically significant for CIV value and LN value in the S0 and S4 stage.As a result,there was no statistically significant difference for PIIINP in either two stages.4.The relevance between the Emean value and the liver fibrosis stage was greater than that between serum fibrosis biomarkers(HA,PIIINP,CIV and LN)(P<0.01),with correlation coefficients of 0.940,0.511,0.464,0.527 and 0.554,respectively.5.The diagnostic cut-off point in the ?S1,?S2,?S3 and =S4 stage of hepatic fibrosis was respectively 8.3Kpa,12.7Kpa,15.3Kpa and 21.2Kpa,whereas AUROC was greater than 0.90,with high sensitivity,specificity and accuracy,significantly better than serum fibrosis biomarkers.6.The Emean value was highly correlated with the S staging of hepatic fibrosis(correlation coefficient "r" : 0.940);modestly correlated with ALB,ALP,ALT,GGT,HA,CIV,PIIINP and LN(P<0.05)(correlation coefficient "r" :-0.349,-0.485,0.519,0.611,0.485,0.475,0.485 and 0.512,respectively);but not correlated with TBIL,DBIL,IBIL,TP,GLB and AST(P>0.05).So the S staging of hepatic fibrosis was the most important factor affecting the Emean value.Conclusion1.The Emean value and serum fibrosis biomarkers(HA,CIV,PIIINP and LN)can be utilized for noninvasive diagnosis of rabbit hepatic fibrosis.The Emean value was more closely related with the liver fibrosis stage than that with serum fibrosis biomarkers,and was more efficient than serum fibrosis biomarkers in the diagnosis.SWE,with high sensitivity,specificity and accuracy,can well distinguish and confirm different hepatic fibrosis severities by quantitative evaluation.2.The S staging of liver fibrosis was the most important factor affecting the Emean value,which shows that SWE can be used to confirm liver fibrosis severities.The results showed that SWE could be used as a quantitative index to evaluate the degree of liver fibrosis.