Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS®/ESCULAP) in hepatic nodules in cirrhotic patients—a prospective multicenter study

Document Type
Issue Date
First published
Issue Year
Strobel, D.
Jung, E.-M.
Ziesch, M.
Praktiknjo, M.
Link, A.
Dietrich, C. F.
Klinger, C.
Schultheiß, M.
Jesper, D.
Schellhaas, B.
Springer Berlin Heidelberg


Hepatocellular carcinoma (HCC) can be diagnosed non-invasively with contrast-enhanced ultrasound (CEUS) in cirrhosis if the characteristic pattern of arterial phase hyperenhancement followed by hypoenhancement is present. Recent studies suggest that diagnosis based on this “hyper-hypo” pattern needs further refinement. This study compares the diagnostic accuracies of standardized CEUS for HCC according to the current guideline definition and following the newly developed CEUS algorithms (CEUS LI-RADS®, ESCULAP) in a prospective multicenter real-life setting.


Cirrhotic patients with liver lesions on B-mode ultrasound were recruited prospectively from 04/2018 to 04/2019, and clinical and imaging data were collected. The CEUS standard included an additional examination point after 4–6 min in case of no washout after 3 min. The diagnostic accuracies of CEUS following the guidelines (“hyper-hypo” pattern), based on the examiner’s subjective interpretation (“CEUS subjective”), and based on the CEUS algorithms ESCULAP and CEUS LI-RADS® were compared.


In total, 470 cirrhotic patients were recruited in 43 centers. The final diagnosis was HCC in 378 cases (80.4%) according to the reference standard (histology 77.4%, MRI 16.4%, CT 6.2%). The “hyper-hypo” pattern yielded 74.3% sensitivity and 63% specificity. “CEUS subjective” showed a higher diagnostic accuracy (sensitivity, 91.5%; specificity, 67.4%; positive predictive value, 92%; negative predictive value, 66%). Sensitivity was higher for ESCULAP (95%) and “CEUS subjective” (91.5%) versus CEUS LI-RADS® (65.2%; p < 0.001). Specificity was highest for CEUS LI-RADS® (78.6%; p < 0.001).


CEUS has an excellent diagnostic accuracy for the non-invasive diagnosis of HCC in cirrhosis. CEUS algorithms may be a helpful refinement of the “hyper-hypo” pattern defined by current HCC guidelines.

Key Points

• Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis.

• The CEUS algorithm ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) showed the highest sensitivity, whereas the CEUS LI-RADS® (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System) algorithm yielded the highest specificity.

• A standardized CEUS examination procedure with an additional examination point in the late phase, after 4–6 min in lesions with no washout after 3 min, is vital.

Journal Title
European Radiology
European Radiology 31.10 (2021): S. 7614-7625. <>
Zugehörige ORCIDs