| Background: The degrees of liver fibrosis are closely associated with the treatment and prognostic of patients with chronic liver diseases.Currently,Liver biopsy is still the golden stander of grading liver fibrosis.However,liver biopsy examination is invasive,painful and can have severity complications.Thus,various indirect methods had been developed for grading liver fibrosis,noninvasively.Elastography technique was widely used to measure the stiffness of biological organisms.Transient elastography(TE),which has noninvasive,fast,and high reproducible merits,is one of elastography techniques.Currently,a handful of studies have evaluated the diagnostic accuracy of TE for grading liver fibrosis in patients with chronic viral hepatitis and shows good diagnostic performance.TE technique was recommended as a noninvasive methods to diagnostic liver fibrosis by the clinic practice guideline of European liver association.However,the TE values and Inter-Quartile Range ratio(IQR%)in the chronic virus hepatitis patients with liver tumor are significant higher than those without.Nevertheless,due to the 1-dimensional natural of TE,it can’t observe liver parenchyma like traditional 2-dimensional ultrasonography,thus no further studies explored this phenomenon.Fibro Touchintegrated in 2-dimensional ultrasonography is also a transient elastography technique,which makes it possible to switch freely the modes between TE and ultrasonograhy.Objective: The aim of the present study is to evaluate the diagnostic performance of TE,using Fibro Touchto measure the parenchyma without liver tumor,for noninvasive staging liver fibrosis in chronic virus-B hepatitis patients with hepatic cellular carcinoma with internal validation.Material and methods: 1.Between May,2015 and August,2015,chronic virus B patients with HCC who were consecutively admitted to our hospital to remove liver tumor were prospectively considered for this study.The present study finally includes 446 eligible patients.The index cohort consist of 228 patients,male 190 and female 98;and the validation cohort consist of 158 patients,male 92 and female 66.TE were performed in each of patients before operation at least fasting 6H.The characters of those patients,serum tests at least fasting 8H and the pathologic results of hepatic tissue were available.2.(1)Ultrasound examination: the patients in a supine position stretched their arms above their head to increase intercostal space.Using convex array probe scan the right hepatic tissues obtaining 2-D image,observing the liver parenchyma and determining the measurement point.The measurement point should be located in right 7 to 9 intercostal space in front and middle axillary axial line avoiding the liver lesions and intrahepatic arteries.(2)Transient Elastograohy examination: the patients were required to keep the same positions with 2-D ultrasound examination to avoid the variation in relative positions of measurement point.One dimention probe coated on coupling medium was perpendicular to the skin of the measurement.Requiring the patients natural breath,the examiner keep the probe steadily with right hand and trigger the sampling switch.The success measurements were those which were sampling 10 times continuously,the success sampling ratio more than 60% and the IQR% less than 30%.(3)Pathological examination: the post-operative pathlogical tissue were sliced and stained conventional.The image was viewed by an experienced pathlogic doctor.Liver fibrosiswas staged on a 0 to 4 scale according to the pathologic diagnosis criteria proposed by the prevention and treatment of viral hepatitis;S0,S1,S2,S3,S4.(4)Laboratory tests: including the indexes of HBV infection,serum indexes and tumor markers.All those biochemic indexes were got by fasting blood sample before operation.3.Continuous variables and Categorical variables were expressed as mean±standard deviation and percentage,respectively.Quantitative data were compared by using either tow-sample t test or the Wilcoxon signed-rank test as appropriate.Difference of measurement data were compared with One-way analysis of variance(ANOVA)method,and pairwise comparison was adjusted by Bonferroni method.Proportions were compared using the χ2 test.Receiver operating characteristic(ROC)curve was used for evaluating the diagnostic accuracy of liver stiffness and selecting cut off values according to the Youden index.Simple factor analysis and multiple linear regression analyzed the possible factors influencing the liver stiffeness.Result: 1.According to the liver fibrosis grading criterion,index cohort includes s0(n=35),s1(n=47),s2(n=83),s3(n=37),s4(86);and the validated cohorts includes s0(n=27),s1(n=18),s2(n=45),s3(n=16),s4(n=53).2.The liver stiffness of the included patients ranges from 2.77-46.51 KPa.Liver stiffness increased with the liver fibrosis degree.There were significant different among each of liver fibrosis degree in index and validated cohort.The spearman relative indexes between liver stiffness and liver fibrosis degrees were 0.69(p<0.01)and 0.75(p<0.01)for index and validated cohort,respectively.3.In index cohort,the area under the ROC curve of TE for diagnosing mild fibrosis,significant fibrosis,sever fibrosis and cirrhosis is 0.89(95%CI0.85-0.93),0.86(95%CI0.82-0.90),0.84(95%CI 0.80-0.88)and 0.85(95%CI0.81-0.89),respectively.In validated cohort,the area under the ROC curve of TE for diagnosing mild fibrosis,significant fibrosis,sever fibrosis and cirrhosis is0.94(95%CI0.90-0.97),0.91(95%CI0.86-0.95),0.87(95%CI0.81-0.92)and 0.86(95%CI 0.79-0.91).4.Multiple linear regression analysis showed that the TBA,HB,PT and the ranks of liver fibrosis were the influencing factors(all p<0.05)in index group.In validation group,multiple linear regression analysis demonstrated that the WBC,TBIL,PBA,APTT and the ranks of liver fibrosis were the influencing factors(all p<0.05).Conclusion: The liver stiffness measured by TE technique integrated in 2-dimensional ultrasonography was significant associated with the ranks of liver fibrosis and had a good diagnostic accuracy for liver fibrosis in chronic virus B patients with HCC.It makes observing liver parenchyma in 2-dimensional untrasonography available before liver stiffness measurements,effectively avoiding the liver tumor and intrahepatic arteries,reducing the unreliable results due improper sampling location. |
