Study of detection times for liver stiffness evaluation by shear wave elastography

AIM: To investigate enough valid measurements (VMs) to assess liver fibrosis in chronic hepatitis B patients (CHB).METHODS: One hundred and twelve CHB patients (25 women, 87 men) with a mean age of 38.43 years received liver stiffness evaluations using real-time shear wave elastography for 10 VMs. All patients underwent liver biopsy. Based on the biopsy pathology, the liver stiffness data obtained from different VMs (1, 2, 3, 5 and 10 times) were compared for the evaluation of liver fibrosis. The correlation between the elastic modulus means of the liver obtained from different VMs of detection at each pathological stage was analysed. The receiver operating characteristic (ROC) curve was employed to determine the diagnostic performance of different VMs of detection, and the areas under the ROC curve of different groups were compared.RESULTS: The liver stiffness values obtained from 1 VM, 2 VMs, 3 VMs, 5 VMs and all 10 VMs for stage F0 were 6.95 ± 2.01 kPa, 6.87 ± 1.83 kPa, 6.90 ± 1.88 kPa, 6.95 ± 1.93 kPa and 7.15 ± 1.89 kPa, respectively (F = 0.043, P = 0.996). For stage F1, these values were 7.12 ± 1.72 kPa, 7.24 ± 1.72 kPa, 7.21 ± 1.74 kPa, 7.10 ± 1.78 kPa and 7.04 ± 1.70 kPa, respectively (F = 0.075, P = 0.990). For stage F2, they were 9.37 ± 3.87 kPa, 9.18 ± 3.68 kPa, 9.19 ± 3.81 kPa, 9.18 ± 3.81 kPa and 9.19 ± 3.53 kPa, respectively (F = 0.012, P = 1.000). For stage F3, these were 11.91 ± 3.88 kPa, 11.78 ± 4.04 kPa, 11.83 ± 4.07 kPa, 11.94 ± 4.17 kPa and 12.00 ± 4.02 kPa, respectively (F = 0.010, P = 1.000). For stage F4, the readings were 19.30 ± 7.63 kPa, 19.40 ± 7.36 kPa, 19.54 ± 7.43 kPa, 19.73 ± 7.21 kPa and 20.25 ± 7.22 kPa, respectively (F = 0.054, P = 0.995). There were no significant differences between these groups. Intraclass correlation coefficients among different pathological stages (F0-F4) with different detection VMs were 0.995, 0.993, 0.996, 0.994 and 0.996, respectively. The mean elasticity values from 1 VM, 2 VMs, 3 VMs, 5 VMs and 10 VMs can accurately distinguish fibrosis stages (F0 vs F1234, F01 vs F234, F012 vs F34 and F0123 vs F4) with no significant differences in the five groups (P > 0.05 for all).CONCLUSION: One VM may be sufficient to assess liver fibrosis by using SWE without any significant loss of accuracy in patients with CHB. However, future studies of larger patient samples are necessary for the validation of this method.     

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.     

Noninvasive assessment of liver fibrosis in children with chronic hepatitis C: Shear wave elastography and APRI versus liver biopsy

Background and study aimsHepatitis C virus (HCV) is a major cause of chronic hepatitis. Although liver histopathological examination remains the reference standard for liver fibrosis assessment, noninvasive means of assessment such as shear wave elastography (SWE) and aspartate aminotransferase–platelet ratio index (APRI) have been developed to reduce the need for biopsy. We evaluated the efficacy of SWE and APRI versus liver biopsy for liver fibrosis assessment in children with chronic HCV infection.Patients and methodsFibrosis staging was performed in 46 children (35 boys, 11 girls; mean age: 15.52 ± 2.71 years) with liver biopsy-proven chronic HCV infection according to the METAVIR system. SWE was performed within 6 months of liver biopsy. APRI scores were calculated using data collected on the day of biopsy.ResultsEighteen children had no or mild fibrosis (<F2, 39.1%) and 28 had significant fibrosis (≥F2, 60.9%), with a significant difference between the corresponding mean APRI scores (0.43 ± 0.23 vs 1.26 ± 1.24; p = 0.043). The APRI scores exhibited a significant correlation with the METAVIR stage (r = 0.630; p < 0.001). The SWE values were significantly higher in those with significant fibrosis than in those with no or mild fibrosis (10.43 vs 4.26 kPa; p < 0.000). These values exhibited significant correlations with the METAVIR stage and APRI score (r = 0.863 and 0.544, respectively; both p < 0.001). For differentiating significant fibrosis, the sensitivity, specificity and positive and negative predictive values for an APRI cutoff value of 0.62 were 46.43%, 94.4%, 92.9% and 53.1%, respectively, and these values for an SWE cutoff value of 7.6 kPa were 55.88%, 100%, 100% and 44.4%, respectively.ConclusionIn the clinical assessment of children, the APRI score and SWE can help differentiate between no or mild fibrosis and significant fibrosis. The routine use of SWE and APRI may help decrease the number of liver biopsies performed.     

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.     

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...     

瞬时弹性成像技术在慢性肝病肝纤维化诊断中的应用进展

肝脏纤维化程度及进展与慢性肝脏疾病的诊断与治疗密切相关。早期诊断肝纤维化程度有助于避免代偿期患者向肝硬化失代偿期发展,也有助于降低肝细胞癌的发生率。目前,临床上评估肝纤维化程度的“金标准”仍为肝脏穿刺活检,但是由于其操作的有创性,以及穿刺后可能出现的多种并发症等多种因素的影响,限制了它在临床研究中的使用。瞬时弹性成像技术无创、安全、有利于动态监测肝纤维化进展、客观评价肝脏纤维化程度,使其在国内外得到了广泛的认同,在临床上具有良好的应用前景。     

瞬时弹性成像技术诊断肝纤维化专家意见

基于肝脏瞬时弹性成像技术(transient elastography,TE)的Fibroscan能够通过检测肝脏硬度值(liver stiffness measurement,LSM)来判断肝纤维化,TE诊断肝炎肝硬化的效能优于FibroTest、 FibroMeter、 HepaScore、APRI、API、FIB-4、Forns指数、Hui指数、代偿性肝硬化指数(CCD等血清生物学标志物[1-7],在我国已被批准用于临床.为促进这一技术在临床上的正确合理应用,中国肝炎防治基金会组织专家撰写了《瞬时弹性成像技术诊断肝纤维化专家意见》,并在郑州召开讨论会进一步修改、定稿.随着临床实践的进展及证据积累,专家委员会将对本意见作进一步完善.     

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.     

Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers

Introduction: Non-invasive assessment of fibrosis is increasingly utilized in clinical practice to diagnose hepatic fibrosis. Non-invasive assessment of liver fibrosis relies on biologic and/or physical properties to assess tissue fibrosis. Serum markers estimate fibrosis by incorporating markers reflecting hepatic function (indirect markers) and/or markers measuring extracellular matrix degradation/fibrogenesis (direct markers). Radiology based techniques relay the mechanical properties and stiffness of a tissue, with increased stiffness associated with more advanced fibrosis.

Areas covered: In this comprehensive review, the recent literature discussing serum markers and elastography-based techniques will be covered. These modalities are also explored in the setting of various liver diseases.

Expert opinion: The etiology of liver disease and clinical context should be taken into consideration when non-invasive markers are incorporated in clinical practice. Non-invasive assessment of fibrosis has been most extensively utilized in hepatitis C, followed by hepatitis B and nonalcoholic fatty liver disease, but its role remains less developed in other etiologies of liver disease such as alcohol-associated liver disease and autoimmune liver disease. The role of non-invasive markers in predicting progression or regression of fibrosis, development of liver-related events and survival needs to be further explored.     

两种超声弹性成像技术诊断慢性乙型肝炎患者肝纤维化价值比较*

目的 探讨瞬时弹性成像和二维剪切波弹性成像用于CHB患者肝纤维化诊断的临床价值。方法 2016年3月～2018年12月我院收治的CHB患者164例,均行瞬时弹性成像和二维剪切波弹性成像检查及肝穿刺活检,采用受试者工作特性(ROC)曲线下面积比较两种超声弹性成像检查诊断不同肝纤维化分期的效能。结果 经肝穿刺活检,在164例CHB患者中,诊断肝组织S₁期50例,S₂期42例,S₃期39例,S₄期33例;瞬时弹性成像检查S₁～S₄期肝纤维化分期的弹性值分别为(6.5±1.1)kPa、(8.6±1.4)kPa、(11.7±1.8)kPa和(16.3±1.8)kPa,二维剪切波弹性成像检查弹性值分别为(5.9±0.8) kPa、(8.1±1.2)kPa、(10.9±1.5)kPa和(16.7±1.9) kPa,两种超声弹性成像检查不同肝纤维化分期弹性值差异无统计学意义(P >0.05);二维剪切波弹性成像检查诊断肝纤维化S₂、S₃和S₄期的ROC曲线下面积(AUC)分别为0.971、0.979和0.973,显著高于瞬时弹性成像检查的0.902、0.906和0.904(P <0.05),其诊断的敏感性分别为90.3%、90.6%和100.0%,特异性分别为95.8%、90.6%和84.5%,而瞬时弹性成像检查诊断则分别为78. 5%、81.3%和73.1%,和93.3%、87.9%和91.0%。结论 二维剪切波弹性成像和瞬时弹性成像检查均可用于慢性乙型肝炎患者的肝纤维化诊断,其临床价值均需要进一步探讨。     

肝脏剪切波弹性成像对慢性乙型肝炎患者肝纤维化的评估价值

目的 探讨应用剪切波弹性成像(SWE)诊断慢性乙型肝炎(CHB)患者肝纤维化的效能.方法 2017年1月～2020年1月我院收治的CHB患者76例,使用超声检测肝脏杨氏模量值,同时行肝活检病理学检查.计算谷草转氨酶/血小板比率指数(APRI)和肝纤维化-4因子指数(FIB-4).采用多因素Logistic回归分析影响肝...     

实时组织弹性成像定量评价大鼠肝纤维化

目的 分析应用实时组织弹性成像技术定量评价大鼠肝纤维化的可行性.方法 应用二甲基亚硝胺对70只Wistar大鼠以50mg/kg的剂量一次性腹膜腔注射,复制大鼠肝纤维化模型作为实验组,10只大鼠腹膜腔一次性注射同等量等渗盐水作为对照组.造模后于第5、7、10、14、21、28天分别随机从实验组中取9～10只、对照组中取1～2只大鼠进行超声弹性检查,记录蓝色区域百分比(％AREA)和肝纤维化指数(LF index).随后处死大鼠,取其肝脏行病理纤维化分期及炎症坏死程度分级.分析弹性特征参数与病理纤维化分期及炎症坏死程度的关系.计量资料(偏态)用中位数(四分位间距)表示;采用Spearman相关分析检验LF index、％AREA与肝纤维化病理分级间的相关性,采用多组间秩和检验检测不同肝纤维化组间的LF index、％AREA的差别并用最小显著差异法进一步行两两比较,对LF index和％AREA的诊断效率行受试者工作特征(ROC)曲线分析.结果 58只大鼠造模成功,其中肝纤维化分级为S1、S2、S3、S4的各有9、13、14、12只,伴或不伴有轻度炎症坏死,其余10只大鼠肝脏发生严重炎症坏死而无纤维化.LF index值和％AREA值均随着肝纤维化程度的增加而增大,各组间差异均具有统计学意义(P＜0.05);Lfindex值、％AREA值与肝纤维化病理分期均具有一定相关性(r=0.643,P=0.000和r=0.662,P=0.000).应用LF index和％AREA诊断肝纤维化S1或更高分级纤维化,其ROC曲线下面积分别为0.943和0.948;用于诊断S2或更高分级纤维化,ROC曲线下面积分别为0.890和0.883;用于诊断S3或更高分级纤维化,ROC曲线下面积分别为0.743和0.772;用于诊断S4,ROC曲线下面积分别为0.821和0.842.10只S0伴严重炎症坏死的大鼠与S0无炎症坏死大鼠的Lfindex及％AREA差异均有统计学意义(p=0.005和P=0.017).结论 实时组织弹性成像技术可定量诊断大鼠肝纤维化,但严重的炎症坏死会影响其准确性.     

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.     

Non-invasive assessment of liver fibrosis and prognosis

Over the past decade, several advances have been made in the non-invasive assessment of liver fibrosis. Both serum markers and imaging-based tissue elastography predict the presence of advanced fibrosis compared with liver biopsy. Serum markers may be indirect or direct markers of liver structure and function. Imaging-based techniques measure liver stiffness as a surrogate for fibrosis and include ultrasound and MRI-based methods. Most non-invasive techniques work well at identifying subjects at the extremes of fibrosis but may not accurately discern intermediate stages. In addition to being a diagnostic tool, elastography may have an evolving role in prognosis. Increasing stiffness is associated with higher rates of liver decompensation, need for transplantation, hepatocellular carcinoma, and death. There are special populations of patients where elastography may serve as a non-invasive method to impart useful clinical information, such as patients after liver transplantation, those with congenital heart disease and those being treated for chronic viral hepatitis. The role of non-invasive markers in accurately predicting the presence of fibrosis in obese patients needs to be further refined.     

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.     

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.     

Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography(Fibroscan~)

Unidimensional transient elastography(TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field.     

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.