Veronica Salvatore

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography.

PURPOSE VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.

The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation.

Clinical impact of ultrasound-related techniques on the diagnosis of focal liver lesions.

Since its introduction in clinical practice, ultrasound technology has greatly impacted patient management, particularly in the case of liver diseases, where hepatologists usually perform ultrasound examinations. Clinicians are increasingly aware of the great potential of ultrasound waves and of the recent innovations that exploit the mechanical properties of ultrasound waves. Thus, at present, not only B-mode ultrasound but also contrast-enhanced ultrasound and, more recently, elastosonography are used worldwide in various settings. This review aims to describe why clinicians should be aware of ultrasound-based techniques, how they should use these techniques for assessing focal liver lesions, and how these techniques impact patient management. We will review the clinical potential of ultrasound-related techniques, starting from lesion detection, moving to characterization, and concluding with their utility in guiding treatments and analyzing their effects.

American College of Radiology Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for the diagnosis of Hepatocellular Carcinoma: a pictorial essay

Author(s): Piscaglia, Fabio; Wilson, Stephanie R; Lyshchik, Andrej; Cosgrove, David; Dietrich, Christoph F; Jang, Hyun-Jung; Kim, Tae Kyoung; Salvatore, Veronica; Willmann, Juergen Karl; Sirlin, Claude B; Kono, Yuko

A benign tumour of the liver mimicking malignant liver disease -cholangiocellular adenoma

Objective. To describe three patients with liver lesions mimicking malignant tumours diagnosed finally, using contrast-enhanced ultrasound, as cholangiocellular adenoma (bile duct adenoma).Material and methods. Focal liver lesions found incidentally in three patients. Contrast-enhanced ultrasound was with use of Siemens or Esaote equipment, low MI technique, after an intravenous bolus of 2.4 ml Sonovue (Bracco, Italy).Results. Lesions were 9 mm, 15 mm and 20 mm in diameter and all were enhanced in the arterial phase and hypo-enhanced in the portal venous and late phases, suggesting their malignant nature. In two patients, no primary liver tumour was found, and in the third patient, previously resected for breast cancer, a tissue specimen was considered useful for characterizing tumour receptors for more targeted chemotherapy, the lesion being assumed metastatic in nature. Transcutaneous core biopsies were performed in all three patients. Pathological analysis (including the reference pathology) revealed cholangiocellular adenoma in all of them.Conclusion. Cholangiocellular adenoma is a rare entity and can be a reason for possible false malignant diagnosis using contrast-enhanced ultrasound. Follow-up examinations are recommended.

Quantification of enhancement of focal liver lesions during contrast-enhanced ultrasound (CEUS). Analysis of ten selected frames is more simple but as reliable as the analysis of the entire loop for most parameters

The aim of the study was to evaluate the reliability of the analysis of only 10 frames rather than of a whole clip in performing quantitative assessment of tumor enhancement of focal liver lesions (FLLs) following ultrasound contrast injection. Contrast-enhanced ultrasonography (CEUS) examinations of 31 FLLs (median diameter: 30mm) were performed. All clips were analyzed and quantified with an early prototype of the SonoLiver software (TomTec GmbH, Munich and Bracco Research SA, Geneva), first evaluating the entire clip then selecting only 10 frames at different time intervals. Enhancement measurements obtained from the analysis of the entire clip or of only 10 frames were closely correlated (r=0.931 and p<0.0001 for Area Under the Curve; r=0.944 and p<0.0001 for Perfusion Index). In conclusion, enhancement quantification of FLLs can be reliably obtained from only 10 frames, rather than the entire clip, at least for most parameters, making such procedure easier for potential routine use.

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

BACKGROUND AND AIMS Whether 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. METHODS Sixteen 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. RESULTS Median 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). CONCLUSIONS The 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.

In hepatocellular carcinoma miR-221 modulates sorafenib resistance through inhibition of caspase-3–mediated apoptosis

Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC. Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC. Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients. Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance. Clin Cancer Res; 23(14); 3953–65. ©2017 AACR.

Relationship between hepatic haemodynamics assessed by Doppler ultrasound and liver stiffness.

AIM We tested the relationship between hepatic haemodynamics assessed by Doppler ultrasonography and liver stiffness assessed by Transient Elastography in hepatitis C related chronic liver disease. METHODS Three liver Doppler ultrasound parameters (hepatic artery resistance index, splenic artery resistance index and waveform pattern in hepatic veins) and liver stiffness measured by Transient Elastography were analysed in one hundred consecutive patients affected by hepatitis C related chronic liver disease. RESULTS Hepatic and splenic arteries resistance indexes correlate significantly (p<0.0001 for both) with liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver stiffness ≤or >13 kPa, whereas a splenic artery resistance index cut-off value of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The coincidental finding of both resistance indexes above the respective cut-off values showed a good accuracy in identifying patients with liver stiffness values >13 kPa (accuracy=78%, +LR=2.90, -LR=0.31). A significant difference in liver stiffness values was evident between patients with triphasic and bi- or monophasic waveform pattern (p=0.005). CONCLUSIONS Hepatic and splenic arteries resistance indexes and the hepatic veins waveform pattern assessed by Doppler ultrasound may provide information similar to that of Transient Elastography in hepatitis C related chronic liver disease.

Bidimensional shear wave ultrasound elastography with supersonic imaging to predict presence of oesophageal varices in cirrhosis

We read with great interest the manuscript by Jansen et al.,1 recently published in Liver International. In keeping with their findings, we also hold liver and spleen elastography (L/S2DSWE) as important tools for the noninvasive assessment of cirrhotic patients. In their work, Jansen1 did not assess the prediction of complications of CSPH, like presence of oesophageal varices (EV). The Baveno VI consensus states that EV may be ruledout when liver stiffness (measured by transient elastography) is <20 kPa and concurrently platelet (PLT) count >150 × 103/mL.2 New elastography technologies, embedded in conventional ultrasound scanners, such as 2DSWE with Aixplorer® Supersonic Imagine (2D SWE.SSI) are appealing, but have not been tested in connection with the Baveno VI recommendations. For this reason, we prospectively tested the role of L/S2DSWE. SSI in ruling out EVs in a cohort of 73 compensated cirrhotic patients and approved by the Ethical Committee of our hospital (93/2013/U/ Sper). Fortyfour out of 73 patients (60.27%) had EV. L2DSWE, S2DSWE and PLT had a modest accuracy to predict the presence of EV when tested individually, showing AUCs of 0.753 (95% CI: 0.6230.883), 0.747 (95% CI: 0.6170.876) and 0.773 (95% CI: 0.6480.898), at best cutoff values of 19 kPa, 38 kPa and 100 × 103/mL, respectively. In the settings of Baveno VI recommendations, L2DSWE.SSI (<20 kPa) and PLT (>150 × 103) ruledout EV with 68.50% accuracy (80% PPV; 95.45% specificity). Adopting instead our own cutoff values (L2DSWE.SSI<19 kPa; PLT>100 × 103), EV were ruledout with 76.71% overall accuracy (87.50% PPV and 95.45% specificity). Considering a stepwise approach (L2D SWE.SSI<19 and PLT>100 × 103=no EV; L2DSWE.SSI>19 and PLT<100 × 103=EV probable), 34 patients remained in the grey zone (L2DSWE.SSI<19 and PLT<100 × 103 or L2DSWE.SSI>19 and PLT>100 × 103). S2DSWE. SSI (</≥38 kPa) was used to further classify these patients falling in the grey zone. With this refined algorithm, EV were ruledout with 83.07% accuracy (77.8% PPV; 84.6% specificity; 86.8% NPV; 80.8% sensitivity) and 54/73 (74%) endoscopies could have been spared overall. These data confirm the conclusion of Jansen et al.,1 pointing out L/S2DSWE as a robust clinical tool for the management of cirrhotic patients. Although both sets of results still need external validations, L/S2DSWE.SSI appears to be a promising noninvasive technique for the assessment of CSPH and EVs in patients with compensated advanced chronic liver diseases. The best cutoff values to be used in the Baveno VI algorithm are still to be agreed and validated in the instance of newer shearwave elastography machines.