Multiparametric Ultrasound for the Noninvasive Diagnosis of Porto-sinusoidal Vascular Liver Disorder

Official title

Explorative Study for the Application of Dynamic Contrast-enhanced Ultrasound for the Noninvasive Diagnosis of Porto-sinusoidal Vascular Liver Disorder

Overview

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

• Device Evaluation 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

Primary outcome measures

• Peak enhancement (PE) measured on DCE-US (VueBox) [Time frame: Baseline]
• Time to peak (TTP) measured on DCE-US (VueBox) [Time frame: Baseline]
• Area under the time-intensity curve (AUC) measured on DCE-US (VueBox) [Time frame: Baseline]
• Wash-in rate (slope) measured on DCE-US (VueBox) [Time frame: Baseline]
• Mean Transit Time measured on DCE-US (VueBox) [Time frame: Baseline]
• Rise Time measured on DCE-US (VueBox) [Time frame: Baseline]
• Wash-out rate measured on DCE-US (VueBox) [Time frame: Baseline]

Secondary outcome measures (5)

• Diagnostic sensitivity and specificity of predefined perfusion parameter cut-offs for identifying PSVD (ROC analysis) [Time frame: Baseline]
• Performance of a multiparametric diagnostic score combining DCE-US parameters, liver stiffness, spleen stiffness, and B-mode ultrasound features [Time frame: Baseline]
• Correlation between quantitative DCE-US parameters and risk of portal vein thrombosis at 12 months. [Time frame: from enrollement to 12 months]
• Incidence of portal vein thrombosis at 12 months [Time frame: From baseline to 12 months]
• Incidence of disease-related complications (ascites decompensation, hepatic encephalopathy, variceal bleeding) at 12 months in both arms [Time frame: From enrollement to 12 months]

Eligibility criteria

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.

Exclusion criteria - Cirrhosis group

• Decompensated cirrhosis or Child-Pugh class C;
• Cryptogenic cirrhosis;
• Presence of other causes of portal hypertension (same list as for PSVD exclusions: history of bone marrow transplantation, Budd-Chiari syndrome or hepatic venous outflow obstruction, hepatic schistosomiasis, Abernethy malformation, hereditary hemorrhagic telangiectasia, sarcoidosis, congenital hepatic fibrosis, chronic cholestatic 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma

Identifiers

NCT: NCT07492862 · 8071

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗