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

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:

1. whether arterial hyperenhancement alone is sufficient for the definite diagnosis of HCC in cirrhosis with CEUS
2. 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
3. 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).

• contrast enhanced ultrasound (CEUS) (Diagnostic test): CEUS with SonoVue following standardized protocol
• MRI (Diagnostic test): CE-MRI following standardized protocol
• Histology (Diagnostic test): diagnostic liver biopsy

Primary outcomes

• Diagnostic value of standardised CEUS-based algorithms for the non-invasive diagnosis of HCC in high-risk patients [2 years]: Diagnostic accuracy, interobserver-variabilty and feasability in clinical routine for CEUS-based algorithms Reference Standard: histology / MRI

Secondary outcomes

• Diagnostic value / dispensability of contrast washout for definite diagnosis of HCC with CEUS [2 years]: 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
• Standardisation of CEUS examinations [2 years]: 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
• Diagnostic accuracy of CEUS in intrahepatic cholangiocellular carcinoma (ICC) [2 years]: 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
• Comparison of two CEUS-based algorithms [2 years]: ESCULAP versus CEUS LI-RADS (diagnostic accuracy, interobserver agreement) Reference Standard: histology / MRI
• Non-inferiority of CEUS versus MRI for non-invasive diagnosis of HCC [2 years]: Comparison of CEUS and MRI for non-invasive diagnosis of HCC (diagnostic accuracy, interobserver agreement) Reference Standard: histology
• Influence of histological grading on contrast enhancement behaviour [2 years]: correlation of histological grading and contrast enhancement pattern

Sex: All, ages: 18 Years to any

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)

• Barbara Schellhaas, MD, Principal investigator, University Hospital Erlangen, Department of Medicine 1
• Deike Strobel, MD, Principal investigator, University Hospital Erlangen, Department of Medicine 1