Mabel Zicchetti

Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: A pilot study

Real‐time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single‐center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty‐one patients met inclusion criteria. On the same day, real‐time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix‐en‐Provence, France), TE using FibroScan (Echosens, Paris, France), and US‐assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0‐F1 versus F2‐F4, F0‐ F2 versus F3‐F4, and F0‐F3 versus F4 for both real‐time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85‐0.96) for SWE and 0.84 (95% CI: 0.76‐0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94‐1.00) for SWE and 0.96 (95% CI: 0.90‐0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93‐1.00) for SWE and 0.96 (95% CI: 0.91‐0.99) for TE (P = 0.48), when comparing F0‐F1 versus F2‐ F4, F0‐ F2 versus F3‐F4, and F0 ‐F3 versus F4, respectively. Conclusion: The results of this study show that real‐time SWE is more accurate than TE in assessing significant fibrosis (≥F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B‐mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. (HEPATOLOGY 2012;56:2125–2133)

Reproducibility of real-time shear wave elastography in the evaluation of liver elasticity.

OBJECTIVE To evaluate the reproducibility of real-time shear wave elastography in assessing liver elasticity in healthy volunteers. METHODS Forty-two volunteers were studied in day 1. Shear wave elastography studies were performed by using the ultrasound system Aixplorer™ (SuperSonic Imagine S.A., Aix-en-Provence, France) with a convex broadband probe. Measurements were carried by two operators, an expert (operator 1) and a novice (operator 2). Examinations were performed on the right lobe of the liver. Each operator performed 10 consecutive measurements in each volunteer. In a subset of volunteers (n=18) measurements were performed twice on two different days (day 1 and day 2). Intraobserver and interobserver agreement were assessed by intraclass correlation coefficient. RESULTS Intraobserver agreement between measurements performed in the same subject in the same day (day 1 or day 2) showed intraclass correlation coefficient values of 0.95 (95% confidence interval, 0.93-0.98) and 0.93 (95% confidence interval, 0.90-0.96) for operator 1 and operator 2, respectively. Intraobserver agreement between measurements performed in the same subject in different days showed intraclass correlation coefficient values of 0.84 (95% confidence interval, 0.69-0.98) and 0.65 (95% confidence interval, 0.39-0.91) for operator 1 and operator 2, respectively. Interobserver agreement was 0.88 (95% confidence interval, 0.82-0.94). CONCLUSIONS The results of this study show that shear wave elastography is a reliable and reproducible noninvasive method for the assessment of liver elasticity. Expert operator had higher reproducibility of measurements over time than novice operator.

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 ≥ 3 and F = 4. The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lins concordance correlation coefficient. RESULTS To assess the performance of PSWE, 134 consecutive 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 47 consecutive 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 from 0.83 (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.

Performance of Real-Time Strain Elastography, Transient Elastography, and Aspartate-to-Platelet Ratio Index in the Assessment of Fibrosis in Chronic Hepatitis C

OBJECTIVE The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively. CONCLUSION Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Ultrasound point shear wave elastography assessment of liver and spleen stiffness: effect of training on repeatability of measurements

AbstractObjectivesTo evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect.MethodsHealthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility.ResultsA total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole.ConclusionsThe results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements.Key Points• Reproducibility of SS measurements depends on the expertise of the operator. • To achieve good reproducibility between measurements a training period is required. • A learning curve in pSWE acquisition should be taken into account. • SS measurements are less reproducible than LS measurements.

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 for F ≥ 2; 7.9 kPa for F ≥ 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 for F ≥ 2; 9.3 kPa for F ≥ 3; 12.3 kPa for F = 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.

Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis.

AIM To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis. METHODS CAP is a new technique that measures the attenuation in the liver of an ultrasound beam, which is directly related to lipid accumulation. Consecutive patients undergoing liver biopsy for chronic viral hepatitis were studied using the M probe of FibroScan device (Echosens, Paris, France). The device estimates liver steatosis in decibel per meter (dB/m). An expert operator performed all measurements. Steatosis was graded according to Kleiners classification. Pearson or Spearman rank coefficient was used to test correlation between two study variables. Linear regression was used for multivariate model to assess the association between CAP and other variables. Receiver operating characteristic curve analysis was performed to calculate area under the curve (AUROC) for S0 vs S1-S3 and S0-S1 vs S2-S3. RESULTS 115 subjects (85 males and 30 females) were prospectively studied. The mean values of CAP were 227.1 ± 43.1 for S0; 254.6 ± 38.9 for S1; 297.8 ± 49.4 dB/m for S2-S3. In univariate analysis CAP showed a significant correlation with age, body mass index (BMI), degree of steatosis, and cholesterol. Multivariate regression analysis confirmed the correlation with the degree of steatosis [coefficient, 1.2 (0.60-1.83); P < 10(-5)] and BMI [coefficient, 4.1 (0.5-7.8); P = 0.03] but not with all other variables. Optimal cutoff values for S ≥ 1 and S ≥ 2 were 219 dB/m [AUROC, 0.76 (0.67-0.84); sensitivity, 91.1% (78.8-97.5); specificity, 51.6% (38.7-64.2); positive predictive value, 56.9% (44.7-68.6); negative predictive value, 89.2% (74.3-97.0); positive likelihood ratio, 1.88 (1.4-2.5); negative likelihood ratio, 0.17 (0.07-0.5)] and 296 dB/m [AUROC, 0.82 (0.74-0.89); sensitivity, 60.0% (32.3-83.7); specificity, 91.5% (83.9-96.3); positive predictive value, 52.9% (27.8-77.0); negative predictive value, 93.5% (86.3-97.6); positive likelihood ratio, 7.05 (3.2-15.4); negative likelihood ratio, 0.44 (0.2-0.8)], respectively. CONCLUSION Controlled attenuation parameter could be a useful tool in the clinical management of patients with chronic viral hepatitis for detecting liver steatosis.

Assessment of liver stiffness with transient elastography by using S and M probes in healthy children

We read with great interest the article by Engelmann etal. [2] in the February 2012 issue of EJP and wouldlike to raise an important issue in relation to their work.In their study, the authors investigated the feasibility oftransient elastography (TE) in healthy children to definenormal values of liver stiffness. Examinations were per-formed by using two types of probes (S or M) depend-ing on thorax circumference and according to themanufacturer recommendations. By using the appropri-ate probe, normal liver stiffness values were 4.40, 4.73,and 5.1 kPa, respectively, in three age groups—namely0–5, 6–11, and 12–18 years. Eighty percent of measure-ments were performed with the S probe and 20 % withthe M probe.Unfortunately, the utilization of different probes (S orM) introduces a severe bias that limits the results of thestudy. Indeed, the values obtained with different probesare not comparable due to technical aspects, such asfocal length, vibration amplitude, and depth of measure-ment [5]. In adults, it has been demonstrated that TEresults obtained by using M and XL probes are system-atically different because of the different region of inter-est [1, 3, 5]. Myers et al. [5] have found that, in patientswho were studied with both probes, the values obtainedwith XL probe were 1–2 kPa lower than that obtainedwith the M probe. It can be inferred that similar differ-ences could also be expected between the S and Mprobes, and this aspect should be taken into accountand thoroughly investigated. On the other hand, in arecent study, in which the results of TE measurementsobtained with an XL probe were compared to that ofliver biopsy, it was found that there was an overestima-tion of liver fibrosis with the XL probe [4].References

Correlation of the controlled attenuation parameter with indices of liver steatosis in overweight or obese individuals: A pilot study

Objective The aim of this study was to assess the clinical relevance of the controlled attenuation parameter (CAP) by analyzing the correlations between CAP and indirect indices of liver steatosis in obese or overweight individuals. Methods Consecutive participants were prospectively enrolled. BMI, waist circumference, hepatic steatosis index, fatty liver index, percent fat mass and regional fat masses as assessed by dual-energy X-ray absorptiometry (DXA), fat signal fraction as assessed by MRI, and CAP were obtained. Pearson’s r coefficient was used to test the correlation between two study variables. Results A total of 88 individuals were studied. They included 31 men [age, 50.4 years (12.9 years); BMI, 30.7 kg/m2 (4.8 kg/m2)] and 57 women [age, 49.0 years (12.6 years); BMI, 31.4 kg/m2 (5.6 kg/m2)]. DXA, anthropometric parameters, and fatty liver index were moderately correlated with CAP in men. In women, there was a moderate correlation of CAP with the hepatic steatosis index and anthropometric parameters and only a slight or fair correlation of CAP with DXA parameters. CAP and fat signal fraction showed a good correlation (r=0.65 in men, P=0.002; r=0.68 in women, P=0.0009). Conclusion Measurement of CAP is a reliable method for noninvasive assessment of liver steatosis, showing a correlation with other indirect markers of central obesity and a good correlation with MRI results.

Liver stiffness assessed by transient elastography in patients with β thalassaemia major

RATIONALE FOR THE STUDY This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by β thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values. MATERIALS AND METHODS The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearsons r coefficient was used to test correlations between liver stiffness measurements and all other variables. RESULTS In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls β thalassaemia major patients had a significant increase in LSMs independently from HCV infection.RATIONALE FOR THE STUDY This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by β thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values. MATERIALS AND METHODS The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearsons rcoefficient was used to test correlations between liver stiffness measurements and all other variables. RESULTS In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls β thalassaemia major patients had a significant increase in LSMs independently from HCV infection.