Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma – A Prospective Multicenter DEGUM Study
Authors: Schellhaas Barbara , Bernatik Thomas , Bohle Wolfram , Borowitzka Fanny , Chang Johannes , Dietrich Christoph F. , Dirks Klaus , Donoval Robert , Drube Kristine , Friedrich-Rust Mireen , Gall Christine , Gittinger Fleur , Gutermann Martin , Haenle Mark Martin , von Herbay Alexandra , Ho Chau Hong , Hochdoerffer Rico , Hoffmann Tatjana , Hüttig Matthias , Janson Christopher , Jung Ernst-Michael , Jung Norbert , Karlas Thomas , Klinger Christoph , Kornmehl Adam , Kratzer Wolfgang , Krug Sebastian , Kunze Georg , Leitlein Jens , Link Alexander , Lottspeich Christian , Marano Aldo , Mauch Martin , Moleda Lukas , Neesse Albrecht , Petzold Golo , Potthoff Andrej , Praktiknjo Michael , Rösner Klaus-Dieter , Schanz Stefan , Schultheiß Michael , Sivanathan Visvakanth , Stock Joachim , Thomsen Thomas , Vogelpohl Johanna , Vogt Christoph , Wagner Siegfried , Wiegard Christiane , Wiesinger Isabel , Will Uwe , Ziesch Matthias , Zimmermann Patrick , Strobel Deike 
Published: July 2020

Abstract
Background This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.
Methods Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System).
Results 321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p < 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p < 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p < 0.001) and CEUS on-site (62.7 %; p < 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site.
Conclusion This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms.