Contrast-Enhanced Ultrasound Patterns for the Non-invasive Diagnosis of Hepatocellular Carcinoma: A Prospective Multicenter Study in Histologically Proven Liver Lesions in a Real-Life Setting Demonstrating the Benefit of Extended Late Phase Observation

The hallmark for the non-invasive diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in cirrhosis is arterial phase hyperenhancement (APHE), followed by late-onset (>60 s), mild washout. Large retrospective studies report this pattern of washout to occur in the vast majority of HCCs. However, a prospective multicenter validation of these findings is still missing. Thus, we initiated a prospective multicenter validation study assessing CEUS enhancement patterns in focal liver lesions of patients at risk for HCC. We analyzed lesions that were eventually histology proven in a real-life setting. CEUS patterns were assessed for subgroups of HCC, intrahepatic cholangiocellular carcinoma (iCCA) and non-HCC, non-iCCA lesions. The diagnosis was HCC in 316 lesions (median size: 40 mm), iCCA in 26 lesions (median size: 47.5 mm) and non-HCC, non-iCCA in 53 lesions (median size: 27 mm). Overall, 85.8% of HCCs exhibited APHE. APHE followed by washout occurred in 72.8% of HCCs and 50% of iCCAs and non-HCC, non-iCCA malignancies (p < 0.05). Early and marked washout was associated more commonly with iCCA; HCCs exhibited mostly late and mild washout (onset >4–6 min in 10% of cases). Our prospective data confirm that the typical pattern of APHE followed by late-onset, mild washout occurs in the majority of HCCs.