Contrast-enhanced Ultrasound, Liver Cirrhosis, Portal Hypertension, Noncirrhotic, Portal Hypertension Related to Cirrhosis, Porto-sinusoidal Vascular Liver Disorder, Ultrasound Elastography
Conditions
Keywords
porto-sinusoidal vascular liver disorder, liver cirrhosis, liver ultrasound, ultrasound elastography, dynamic contrast-enhanced ultrasound, chronic liver disease
Brief summary
Porto-sinusoidal vascular disease (PSVD) is a rare clinical entity characterized by significant portal hypertension in the absence of cirrhosis on liver histology, which may or may not show specific alterations of the portal vein, sinusoids, or hepatic lobular architecture. Currently, diagnosis of this condition necessarily requires a liver biopsy and, despite some differences detected on imaging studies-and particularly on liver and spleen elastography-PSVD remains indistinguishable from cirrhosis using non-invasive tests. Contrast-enhanced ultrasound (CEUS) is an easy-to-perform, repeatable, and cost-effective examination that enables real-time assessment of parenchymal or focal liver lesion perfusion. Moreover, the application of dynamic contrast-enhanced ultrasound (DCE-US-i.e., contrast-enhanced ultrasound followed by quantitative perfusion analysis using dedicated software, such as the VueBox Software that will be used in this study) allows integration of CEUS qualitative assessment with quantitative evaluation of tissue perfusion through analysis of time-intensity curves generated during contrast transit. From this analysis, several perfusion-related parameters can be derived (for example, peak enhancement, time to peak, or area under the curve), which have already proven useful in improving differential diagnosis of focal liver lesions and in predicting treatment response and systemic therapy outcomes. To date, the use of DCE-US for the diagnosis of PSVD has not yet been described; however, based on the underlying histological alterations associated with this disease, it is reasonable to hypothesize that parameters obtained with this technique in the liver parenchyma of patients with PSVD may differ from those measured in patients with liver cirrhosis. The aim of the present project is to apply DCE-US in patients with PSVD and in patients with cirrhosis to evaluate potential significant differences in perfusion parameters, and to assess the feasibility of a non-invasive differential diagnosis between the two conditions using this technique in combination with elastography and bidimensional ultrasound data to develop a multiparametric diagnostic score.
Interventions
DEVICEEvaluation of quantitative perfusion parameters at dynamic contrast-enhanced ultrasound through Vuebox Software
Patients from the two arms will undergoing dynamic contrast-enhanced ultrasound, and CEUS videoclips will be analyzed through the software VueBox to evaluate perfusion parameters. These parameters will be compared among the two arms and integrated with other ultrasound-derived data to analyze differences and to elaborate a multiparametric diagnostic score
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- PSVD group * Histologically confirmed diagnosis of porto-sinusoidal vascular disease (PSVD); * Presence of clinically significant portal hypertension, evidenced by at least one specific sign of portal hypertension (e.g., imaging evidence of collateral circulation or porto-systemic shunts, endoscopic evidence of esophageal or gastric varices, or history of gastrointestinal variceal bleeding); * Age ≥ 18 years; * Ability to understand the study information and provide written informed consent; Inclusion criteria - Cirrhosis group * Diagnosis of liver cirrhosis confirmed by liver histology or, alternatively, by compatible findings on imaging, laboratory tests, and physical examination together with a positive history for at least one known cause of chronic liver disease; * Presence of clinically significant portal hypertension, evidenced by at least one specific sign of portal hypertension (e.g., imaging evidence of collateral circulation or porto-systemic shunts, endoscopic evidence of esophageal or gastric varices, or history of gastrointestinal variceal bleeding); * Age ≥ 18 years; * Ability to understand the study information and provide written informed consent.
Exclusion criteria
- PSVD group (cases) * Presence of other causes of portal hypertension, including but not limited to: history of bone marrow transplantation, Budd-Chiari syndrome or hepatic venous outflow obstruction, hepatic schistosomiasis, Abernethy malformation, hereditary hemorrhagic telangiectasia, sarcoidosis, congenital hepatic fibrosis, or chronic cholestatic liver diseases; * Presence of portal, spleno-mesenteric, or hepatic vein thrombosis; * Prior hepatic or splenic surgery; * Presence of primary or secondary malignant liver tumors; * Presence of a transjugular intrahepatic portosystemic shunt (TIPS) device; * Congenital anomalies of the liver or biliary tract; * History of heart failure; * Contraindications to administration of SonoVue (sulfur hexafluoride microbubbles), including: prior allergic reaction to the active substance or any excipients, known right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \> 90 mmHg), uncontrolled systemic hypertension, or adult respiratory distress syndrome; * Inadequate sonographic visualization of the right hepatic lobe; * Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak enhancement (PE) measured on DCE-US (VueBox) | Baseline | Maximum intensity of the signal in the time-intensity curve at dynamic contrast-enhanced ultrasound |
| Time to peak (TTP) measured on DCE-US (VueBox) | Baseline | The time required from the beginning of the exam to reach the peak enhancement |
| Area under the time-intensity curve (AUC) measured on DCE-US (VueBox) | Baseline | The total area under the time-intensity curve reflecting the quantity of contrast media passed through the region of interest |
| Wash-in rate (slope) measured on DCE-US (VueBox) | Baseline | Tangent at the ascending part of the time-intensity curve |
| Mean Transit Time measured on DCE-US (VueBox) | Baseline | Mean time taken by contrast to pass through the ROI |
| Rise Time measured on DCE-US (VueBox) | Baseline | Time from peak enhancement to point where tangent of ascending curve across x-axis |
| Wash-out rate measured on DCE-US (VueBox) | Baseline | The tangent at the descending part of the time-intensity curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic sensitivity and specificity of predefined perfusion parameter cut-offs for identifying PSVD (ROC analysis) | Baseline | Differences among PSVD and cirrhosis in perfusion parameters will be analyzed in order to identify the cut-offs with the best sensitivity and specificity to identify PSVD from DCE-US. |
| Performance of a multiparametric diagnostic score combining DCE-US parameters, liver stiffness, spleen stiffness, and B-mode ultrasound features | Baseline | The mentioned cut-offs in DCE-US parameters will be combined with the bidimensional ultrasound data, Doppler data and elastography data to elaborate a noninvasive diagnostic score to predict the presence of PSVD |
| Correlation between quantitative DCE-US parameters and risk of portal vein thrombosis at 12 months. | from enrollement to 12 months | DCE-US parameters will be correlated with the incidence of portal vein thrombosis in order to detect if these parameters may be predictive of developing this condition, potentially allowing to identify the cohort of patients who would benefit more from prophylactic anticoagulation |
| Incidence of portal vein thrombosis at 12 months | From baseline to 12 months | The proportion of patients developing porta vein thrombosis at 12 months |
| Incidence of disease-related complications (ascites decompensation, hepatic encephalopathy, variceal bleeding) at 12 months in both arms | From enrollement to 12 months | Nunmber of portal hypertension-related complications per patient in both arms from the enrollement to 12 months |
Countries
Italy
Contacts
CONTACTMaria Assunta Zocco
PRINCIPAL_INVESTIGATORMaria Assunta Zocco
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Outcome results
None listed