Standardized CEUS Algorithms for Diagnosis of HCC - Prospective German Multicenter Study

Study Overview
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Brief Summary
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Aim of this prospective national multicenter study is to improve standardization of contrast-enhanced ultrasound (CEUS) in the non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. The study is funded by the German Society for Ultrasound in Medicine (DEGUM).

Detailed Description
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To date, CEUS criteria for non-invasive diagnosis of HCC include arterial phase hyperenhancement, followed by contrast washout in the portal venous or late phase. We would like to investigate the following points: whether arterial hyperenhancement alone is sufficient for the definite diagnosis of HCC in cirrhosis with CEUS whether a further clearly-defined point of assessment in the late phase after 4-6 minutes is of additional diagnostic value in focal liver lesions showing no contrast washout after 3 minutes diagnostic value of CEUS-based standardised diagnostic algorithms (ESCULAP = Erlanger Synopsis of Contrast Enhanced Ultrasound for Liver lesion Assessment in Patients at risk; CEUS LI-RADS = Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System) for non-invasive diagnosis of HCC in high-risk patients (diagnostic accuracy, interobserver-variability, feasability in clinical Routine).

Official Title
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Standardized Contrast-enhanced Ultrasound (CEUS) -Algorithms for the Non-invasive Diagnosis of Hepatocellular Carcinoma (HCC) in High-risk-patients - a Prospective German Multicenter Study

Conditions
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Liver Cirrhosis, Hepatocellular Carcinoma, Cholangiocarcinoma, Intrahepatic, Liver Cancer, Liver Neoplasms, Liver Diseases

Intervention / Treatment
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* Diagnostic Test: contrast enhanced ultrasound (CEUS)
* Diagnostic Test: MRI
* Diagnostic Test: Histology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: high risk for HCC focal liver lesion on B-mode ultrasound Exclusion Criteria: pre-treated HCC lesion systemic therapy for HCC (sorafenib, regorafenib and others)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients at risk for HCC<br>Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology | Diagnostic Test: contrast enhanced ultrasound (CEUS)<br>* CEUS with SonoVue following standardized protocol<br>Diagnostic Test: MRI<br>* CE-MRI following standardized protocol<br>Diagnostic Test: Histology<br>* diagnostic liver biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic value of standardised CEUS-based algorithms for the non-invasive diagnosis of HCC in high-risk patients | Diagnostic accuracy, interobserver-variabilty and feasability in clinical routine for CEUS-based algorithms Reference Standard: histology / MRI | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic value / dispensability of contrast washout for definite diagnosis of HCC with CEUS | Sensitvity, specificity, positive and negative predictive value of arterial hyperenhancement only compared with arterial hyperenhancement followed by contrast washout for non-invasive diagnosis of HCC in high-risk patients Reference Standard: histology / MRI | 2 years | 
| Standardisation of CEUS examinations | Diagnostic value of an additional standardised examination point in the late phase after 4-6 minutes in lesions without contrast washout after 3 minutes Reference Standard: histology / MRI | 2 years | 
| Diagnostic accuracy of CEUS in intrahepatic cholangiocellular carcinoma (ICC) | Sensitvity, specificity, positive and negative predictive value of contrast-enhanced ultrasound for non-invasive diagnosis of ICC in high-risk patients / differential diagnosis of HCC versus ICC Reference Standard: histology | 2 years | 
| Comparison of two CEUS-based algorithms | ESCULAP versus CEUS LI-RADS (diagnostic accuracy, interobserver agreement) Reference Standard: histology / MRI | 2 years | 
| Non-inferiority of CEUS versus MRI for non-invasive diagnosis of HCC | Comparison of CEUS and MRI for non-invasive diagnosis of HCC (diagnostic accuracy, interobserver agreement) Reference Standard: histology | 2 years | 
| Influence of histological grading on contrast enhancement behaviour | correlation of histological grading and contrast enhancement pattern | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESCULAP, MRI, contrast-enhanced ultrasound, non-invasive diagnosis, focal liver lesion, liver cirrhosis, standardised diagnostic algorithm, intrahepatic cholangiocellular carcinoma, CEUS LI-RADS, imaging, hepatocellular carcinoma, diagnostic accuracy, interobserver agreement, Erlanger Synopsis of CEUS for Liver lesion Assessment in Patients at risk, CEUS Liver Imaging Reporting and Data System