Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography

Two-dimensional shear wave elastography(2D-SWE) is a rapid, simple and novel noninvasive method that has been proposed for assessing hepatic fibrosis in patients with chronic liver diseases(CLDs) based on measurements of liver stiffness. 2 D-SWE can be performed easily at the bedside or in an outpatient clinic and yields immediate results with good reproducibility. Furthermore, 2 D-SWE was an efficient method for evaluating liver fibrosis in small to moderately sized clinical trials. However, the quality criteria for the staging of liver fibrosis are not yet well defined. Liver fibrosis is the main pathological basis of liver stiffness and a key step in the progression from CLD to cirrhosis; thus, the management of CLD largely depends on the extent and progression of liver fibrosis. 2 D-SWE appears to be an excellent tool for the early detection of cirrhosis and may have prognostic value in this context. Because 2 D-SWE has high patient acceptance, it could be useful for monitoring fibrosis progression and regression in individual cases. However, multicenter data are needed to support its use. This study reviews the current status and future perspectives of 2 D-SWE for assessments of liver fibrosis and discusses the technical advantages and limitations that impact its effective and rational clinical use.     

Point shear wave elastography method for assessing liver stiffness

AIM:To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness.METHODS:This was a single-center,cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy(LB)(Group 1)and healthy volunteers(Group 2)were studied.In each subject 10 consecutive point shear-wave elastography(PSWE)measurements were performed using the iU22 ultrasound system(Philips Medical Systems,Bothell,WA,United States).Patients in Group 1 underwent PSWE,transient elastography(TE)using FibroScan(Echosens,Paris,France)and ultrasound-assisted LB.For the assessment of PSWE reproducibility two expert raters(rater 1 and rater 2)independently performed the examinations.The performance of PSWE was compared to that of TE using LB as a reference standard.Fibrosis was staged according to the METAVIR scoring system.Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve(AUC)for F≥2,F≥3and F=4.The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin’s concordance correlation coefficient.RESULTS:To assess the performance of PSWE,134consecutive patients in Group 1 were studied.The median values of PSWE and TE(in kilopascals)were 4.7(IQR=3.8-5.4)and 5.5(IQR=4.7-6.5),respectively,in patients at the F0-F1 stage and 3.5(IQR=3.2-4.0)and 4.4(IQR=3.5-4.9),respectively,in the healthy volunteers in Group 2(P<10-5).In the univariate analysis,the PSWE and TE values showed a high correlation with the fibrosis stage;low correlations with the degree of necroinflammation,aspartate aminotransferase and gamma-glutamyl transferase(GGT);and a moderate negative correlation with the platelet count.A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables.The following AUC values were found:0.80(0.71-0.87)for PSWE and 0.82(0.73-0.89)for TE(P=0.42);0.88(0.80-0.94)for PSWE and 0.95(0.88-0.98)for TE(P=0.06);and 0.95(0.89-0.99)for PSWE and 0.92(0.85-0.97)for TE(P=0.30)for F≥2,F≥3 and F=4,respectively.To assess PSWE reproducibility,116 subjects were studied,including 47consecutive patients scheduled for LB(Group 1)and 69 consecutive healthy volunteers(Group 2).The intraobserver agreement ranged from 0.83(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 1 and from 0.84(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 2.The interobserver agreement yielded values from0.83(95%CI:0.78-0.88)to 0.93(95%CI:0.91-0.95).CONCLUSION:PSWE is a reproducible method for assessing liver stiffness,and it compares with TE.Compared with patients with nonsignificant fibrosis,healthy volunteers showed significantly lower values.     

Assessment of biopsy proven liver fibrosis by two-dimensional shear wave elastography in patients with primary biliary cholangitis

BackgroundTwo-dimensional shear-wave elastography (2D-SWE) is an ultrasound-based technique used to stage liver fibrosis by measuring liver stiffness (LS). The diagnostic performance of 2D-SWE for assessing liver fibrosis in patients with primary biliary cholangitis (PBC) has not been reported before.AimsTo investigate the diagnostic performance of 2D-SWE for staging liver fibrosis in patients with PBC by using histologic analysis as a reference standard.MethodsPatients with PBC who underwent liver biopsy and 2D-SWE were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. Areas under receiver operating characteristic curve (AUROC) was constructed to assess the accuracy of 2D-SWE and serum fibrosis models for staging liver fibrosis.ResultsThe diagnostic performance characteristics were determined for 157 patients with PBC. The AUROCs of LS measured by 2D-SWE for significant fibrosis, severe fibrosis, and cirrhosis were 0.88, 0.97 and 0.99, respectively. The cutoff values of LS measured by 2D-SWE in discriminating significant fibrosis, severe fibrosis, and cirrhosis were 10.7 kPa, 12.2 kPa and 14.1 kPa, respectively. The diagnostic accuracy of 2D-SWE for staging liver fibrosis was 73.9%.Conclusions2D-SWE is an efficient noninvasive method for the assessment of liver fibrosis in patients with PBC.     

Role of two-dimensional shear wave elastography in chronic liver diseases: A narrative review

Liver biopsy is the gold standard for evaluating the degree of liver fibrosis in patients with chronic liver disease. However, due to the many limitations of liver biopsy, there has been much interest in the use of noninvasive techniques for this purpose. Among these techniques real-time two-dimensional shear wave elastography(2D-SWE) has the advantage of measuring tissue elasticity with the guidance of B-mode images. Recently, many studies have been conducted on the application of 2D-SWE in patients with various liver diseases, and their validity has been confirmed. Here, we briefly discuss the role of 2D-SWE in patients with chronic liver diseases, particularly aspects of the examination techniques and clinical applications.     

Quantitative evaluation of pancreatic tumor fibrosis using shear wave elastography

Background & aimsThere is no established non-invasive method for diagnosis of pancreatic fibrosis. Shear wave elastography (SW-EG) may be a candidate for this purpose. The aims of this study were to assess the reproducibility of SW-EG in the normal imaging pancreas (Phase 1) and to evaluate the diagnostic performance of SW-EG for pancreatic fibrosis classified histologically (Phase 2).MethodsPhase 1: This included 127 cases that underwent SW-EG of the normal imaging pancreas. SW-EG was measured at least five times in the pancreatic parenchyma and the median of repeated measurements was defined as the pancreatic elastic modulus (PEM). Phase 2: This included 53 cases that underwent SW-EG of the pancreatic parenchyma preoperatively and in which pancreas parenchyma were evaluated histologically. Histological fibrosis was graded in 4 stages: normal, mild, moderate, and severe.ResultsPhase 1: Median PEM in the head, body, and tail of the pancreas were 3.23, 3.17, and 2.91 kPa, respectively, with no significant difference among regions (P = 0.554). The intraclass correlation coefficient showed good reproducibility (ρ = 0.71) after 5 measurements. Phase 2: There was a significant positive correlation between PEM and the histological pancreatic fibrosis stage (r_s = 0.63, P < 0.001). Areas under the receiver operating characteristic curve for the accuracy of SW-EG for diagnosis of pancreatic fibrosis were 0.85 (≥mild), 0.84 (≥moderate), and 0.87 (severe).ConclusionSW-EG can be used to determine the stage of pancreatic fibrosis non-invasively with high accuracy and reproducibility.     

Real time shear wave elastography in chronic liver diseases: Accuracy for predicting liver fibrosis,in comparison with serum markers

AIM: To evaluate the correlation between liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) and liver fibrosis stage and the accuracy of LSM for predicting significant and advanced fibrosis, in comparison with serum markers.METHODS: We consecutively analyzed 70 patients with various chronic liver diseases. Liver fibrosis was staged from F0 to F4 according to the Batts and Ludwig scoring system. Significant and advanced fibrosis was defined as stage F ≥ 2 and F ≥ 3, respectively. The accuracy of prediction for fibrosis was analyzed using receiver operating characteristic curves.RESULTS: Seventy patients, 15 were belonged to F0-F1 stage, 20 F2, 13 F3 and 22 F4. LSM was increased with progression of fibrosis stage (F0-F1: 6.77 ± 1.72, F2: 9.98 ± 3.99, F3: 15.80 ± 7.73, and F4: 22.09 ± 10.09, P < 0.001). Diagnostic accuracies of LSM for prediction of F ≥ 2 and F ≥ 3 were 0.915 (95%CI: 0.824-0.968, P < 0.001) and 0.913 (95%CI: 0.821-0.967, P < 0.001), respectively. The cut-off values of LSM for prediction of F ≥ 2 and F ≥ 3 were 8.6 kPa with 78.2% sensitivity and 93.3% specificity and 10.46 kPa with 88.6% sensitivity and 80.0% specificity, respectively. However, there were no significant differences between LSM and serum hyaluronic acid and type IV collagen in diagnostic accuracy.CONCLUSION: SWE showed a significant correlation with the severity of liver fibrosis and was useful and accurate to predict significant and advanced fibrosis, comparable with serum markers.     

Differences in liver stiffness values obtained with new ultrasound elastography machines and Fibroscan: A comparative study

Background and aimsWhether Fibroscan thresholds can be immediately adopted for none, some or all other shear wave elastography techniques has not been tested. The aim of the present study was to test the concordance of the findings obtained from 7 of the most recent ultrasound elastography machines with respect to Fibroscan.MethodsSixteen hepatitis C virus-related patients with fibrosis ≥2 and having reliable results at Fibroscan were investigated in two intercostal spaces using 7 different elastography machines. Coefficients of both precision (an index of data dispersion) and accuracy (an index of bias correction factors expressing different magnitudes of changes in comparison to the reference) were calculated.ResultsMedian stiffness values differed among the different machines as did coefficients of both precision (range 0.54–0.72) and accuracy (range 0.28–0.87). When the average of the measurements of two intercostal spaces was considered, coefficients of precision significantly increased with all machines (range 0.72–0.90) whereas of accuracy improved more scatteredly and by a smaller degree (range 0.40–0.99).ConclusionsThe present results showed only moderate concordance of the majority of elastography machines with the Fibroscan results, preventing the possibility of the immediate universal adoption of Fibroscan thresholds for defining liver fibrosis staging for all new machines.     

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices

BackgroundThe aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE).MethodsBetween January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE.ResultsThe area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701–0.810) and 0.813 (95% CI, 0.763–.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621–0.738) and 0.834 (95% CI, 0.785–0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed.ConclusionsThe diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.     

声触诊弹性成像检测肝脾硬度诊断慢性乙型肝炎患者肝纤维化效能分析

目的 探讨应用声触诊弹性成像(APE)行肝脏硬度检测(LSM)和脾脏硬度检测(SSM)诊断慢性乙型肝炎(CHB)患者肝纤维化的效能.方法 2020年1月～2021年10月我院诊治的CHB患者392例,行肝穿刺组织病理学检查,将≤F1期为非显著性肝纤维化,≥F2期为显著性肝纤维化,F4期为早期肝硬化.使用超声APE计数获...     

Shear wave elastography results correlate with liver fibrosis histology and liver function reserve

AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032). CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.     

Performance of liver stiffness measurements by transient elastography in chronic hepatitis

AIM:To compare results of liver stiffness measurements by transient elastography(TE) obtained in our patients population with that used in a recently published meta-analysis.METHODS:This was a single center cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled.TE was carried out by using FibroScan(Echosens,Paris,France).Liver biopsy was performed on the same day as TE,as day case procedure.Fibrosis was staged according to the Metavir scoring system.The diagnostic performance of TE was assessed by using receiver operating characteristic(ROC) curves and the area under the ROC curve analysis.RESULTS:Two hundred and fifty-two patients met the inclusion criteria.Six(2%) patients were excluded due to unreliable TE measurements.Thus,246(171 men and 75 women) patients were analyzed.One hundred and ninety-five(79.3%) patients had chronic hepatitis C,41(16.7%) had chronic hepatitis B,and 10(4.0%) were coinfected with human immunodeficiency virus.ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa forF ≥ 2;7.9 kPa forF ≥ 3;9.6 kPa for F = 4 in all patients(n = 246),and as high as 6.9 kPa for F ≥ 2;7.3 kPa for F ≥ 3;9.3 kPa for F = 4 in patients with hepatitis C(n = 195).Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2;9.6 kPa for F ≥ 3;12.2 kPa for F = 4 in all patients(n = 246),and as high as 7.0 kPa forF ≥ 2;9.3 kPa forF ≥ 3;12.3 kPa forF = 4 in patients with hepatitis C(n = 195).CONCLUSION:The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.     

Rational arrangement of measuring shear wave speed in the liver

BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.     

实时剪切波弹性成像检测的肝脏硬度与食管静脉曲张程度的相关性

目的 应用实时剪切波弹性成像测量慢性乙型肝炎重度及肝硬化患者的肝脏硬度(LS),探讨其评价患者食管静脉曲张(EV)的存在及其严重程度的价值. 方法 根据胃镜结果将256例慢性乙型肝炎重度及肝硬化患者分为无EV组、轻度EV组、中-重度EV组,分析各组患者的LS、门静脉内径(PV)、脾静脉内径(SV)、肝纤维化指标与EV程度的相关性.计数资料采用x2检验;计量资料三组间均数比较采用单因素方差分析,多重比较采用LSD检验;相关性分析采用双变量Pearson法线性相关分析;用受试者工作特征(ROC)曲线和ROC曲线下面积来评价各项指标的预测能力. 结果 LS、PV、SV在三组间两两比较的差异均有统计学意义(F值分别为137.86,44.77,73.88,P值均＜0.01);患者年龄、Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(LN)和透明质酸(HA)在无EV组和轻度EV组间的差异无统计学意义(P值均＞0.05),而其余组两两比较的差异有统计学意义(P值均＜ 0.05);患者性别、Ⅲ型前胶原N端肽(PCⅢNP)在三组间比较的差异均无统计学意义(P值均＞ 0.05).EV程度与LS、PV、SV、Ⅳ-C、LN、HA呈显著正相关(P值均＜0.01),且LS与EV程度相关性最高(r=0.689,P＜0.01).PCⅢNP与EV程度不相关(P＞0.05).LS曲线下面积为0.923,其预测EV程度的能力比PV、SV、LN、Ⅳ-C、HA、PCⅢNP强,当LS＞7.55 kPa时,诊断轻度EV的敏感度为90.5％,特异度为60％;LS＞18.85kPa时,诊断中-重度EV的敏感度为82.4％,特异度为90.5％. 结论 实时剪切波弹性成像测量LS是预测肝病患者EV的存在及其严重程度的有效检查,可作为评价肝硬化患者EV初始筛查的非侵入性检查方法.     

An initial trial of quantitative evaluation of autoimmune pancreatitis using shear wave elastography and shear wave dispersion in transabdominal ultrasound

Background/ObjectivesWe aimed to examine therapeutic efficacy and prognosis prediction of autoimmune pancreatitis (AIP) using shear wave elastography (SWE) and shear wave dispersion (SWD) in transabdominal ultrasound (US).MethodsThe subjects were 23 patients with diffuse type 1 AIP who underwent SWE and SWD, and 34 controls with a normal pancreas. Elasticity and dispersion were defined as the pancreatic elastic modulus (PEM) and dispersion slope, respectively. PEM and dispersion slope were compared between AIP and control cases, and the short-term therapeutic effect and long-term prognosis were examined.ResultsPEM (30.9 vs. 6.6 kPa, P < 0.001) and dispersion slope (15.3 vs. 13.0 (m/sec)/kHz, P = 0.011) were significantly higher in AIP cases than in controls. Among the 17 AIP patients followed-up in two weeks after treatment, these parameters were 12.7 kPa and 10.5 (m/sec)/kHz with median decrease rate of 37.2% and 32.8%, respectively, which were significantly higher than the change in the size of pancreatic parenchyma (14.4%, P = 0.026). Fourteen of these subjects were followed up for >12 months, during which 2 had relapse; diabetes improved in 5 and worsened in 2; in 60% of cases, the pancreatic parenchyma was atrophied. The % change in PEM after two weeks was tended to be higher in non-atrophy cases.ConclusionSWE and SWD measurement in US may be useful for quantitative assessment of AIP and evaluation of short-term treatment efficacy.