Contrast-Enhanced Ultrasound Algorithms for the Noninvasive Diagnosis of Hepatocellular Carcinoma in High-Risk Patients - A Prospective Multicentre Study (DEGUM CEUS HCC Trial) - European Medical Journal

Contrast-Enhanced Ultrasound Algorithms for the Noninvasive Diagnosis of Hepatocellular Carcinoma in High-Risk Patients – A Prospective Multicentre Study (DEGUM CEUS HCC Trial)

2 Mins
EMJ Hepatology [Supplement 2] ILC Congress Review 2020
*Barbara Schellhaas,1 Deike Strobel,1 DEGUM CEUS HCC Study Group1-44

The authors have declared no conflicts of interest.


The authors would like to thank the German Society for Ultrasound in Medicine (DEGUM) for their support of this study and all participating centres for their efforts.


The study received financial support in the form of a grant from the DEGUM.

EMJ Hepatol. ;8[Suppl 2]:39-40. Abstract Review No: AR6.
Contrast-enhanced ultrasound (CEUS), CEUS algorithms, CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS®), Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk (ESCULAP) guidelines, hepatocellular carcinoma (HCC), imaging, noninvasive diagnosis.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.


Hepatocellular carcinoma (HCC) can be diagnosed noninvasively in high-risk patients by means of contrast-enhanced imaging. The enhancement pattern considered typical of HCC is defined as arterial phase hyperenhancement, followed by contrast washout in the portal venous or late phase.1 More recent studies suggest that washout in HCC is of mild intensity and often occurs in the late phase (after 4–6 minutes); in particular, well-differentiated HCC may show no washout at all. Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the differential diagnosis of HCC.2-5 However, standardisation of the CEUS examination procedure is insufficient, and CEUS-based diagnosis is often accused of being subjective. Recently, standardised CEUS-algorithms (Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk [ESCULAP], Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System [CEUS LI-RADS®]) have been developed to improve the interpretation and reporting of CEUS in HCC-suspect lesions.6-8 However, these algorithms have not yet been validated prospectively in a clinical setting.


Here the authors initiated a prospective, nation-wide, multicentre study, funded by the German Society for Ultrasound in Medicine (DEGUM), intended to improve the standardisation of the CEUS examination procedure, and assess the diagnostic value of CEUS and the new standardised  CEUS-algorithms for the noninvasive diagnosis of HCC.


Patients at risk for HCC, with histologically proven focal liver lesions, upon B-mode ultrasound imaging were prospectively assessed with CEUS following standardised examination protocols in 43 German centres. Clinical data, findings from B-mode ultrasound, CEUS, categorisation according to the CEUS algorithms ESCULAP and CEUS LI-RADS, and histology were entered into online entry forms. CEUS-based diagnosis was compared to histology as the reference standard.


The study prospectively enrolled 395 patients (male/female: 329/66; mean age: 67.2±10.5 years; liver cirrhosis: 76.5%). Mean tumour size was 57.6 mm (range: 5–200 mm; <2 cm, n=42; 61.3% solitary). Histological diagnosis showed HCC in 316 cases and intrahepatic cholangiocellular carcinoma in 26 cases; 34 lesions (8.6%) were benign. Of the cases with HCC, 271 (85.8%) displayed arterial phase hyperenhancement and 255 (80.7%) showed contrast washout. The typical ‘hyper–hypo’ pattern was found in 72.2% of HCC (positive predictive value: 87.4%), and the ‘hyper–iso’ pattern in 13.6% (positive predictive value: 86%). Furthermore, 33 HCC (10.4%) showed late onset of washout after 4–6 minutes. The highest sensitivity for the diagnosis of HCC was reached with the ESCULAP algorithm (94.2%) and subjective on-site interpretation of CEUS (90.2%). The CEUS LI-RADS algorithm yielded the highest specificity (81.8%), but poorest sensitivity (61.8%) and negative predictive value (35.3%). The algorithms showed consensus in 67.1% of cases and one-third of the HCC were correctly identified with ESCULAP alone.


Arterial phase hyperenhancement is the key diagnostic feature of HCC in CEUS. The positive predictive value of the hyper–iso pattern is similar to that of the hyper–hypo pattern. The standardised CEUS algorithms add little diagnostic benefit to conventional on-site interpretation of CEUS. Additional late-phase assessment of washout after 4–6 minutes increases the diagnostic accuracy of CEUS for HCC and should be routinely performed.

Greten TF et al. [Diagnosis of and therapy for hepatocellular carcinoma]. Z Gastroenterol. 2013;51(11):1269-326. (In German). Strobel D et al. Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-enhanced ultrasound (CEUS). Ultraschall Med. 2009;30(4):376-82. Giorgio A et al. Contrast-enhanced ultrasound: a simple and effective tool in defining a rapid diagnostic work-up for small nodules detected in cirrhotic patients during surveillance. J Gastrointestin Liver Dis. 2016;25(2):205-11. Leoni S et al. Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted? Ultraschall Med. 2013;34(3):280-7. Wildner D et al. CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients - early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med. 2015;36(2):132-9. Schellhaas B et al. Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS. Eur J Gastroenterol Hepatol. 2017;29(0):1036-44. Schellhaas B et al. Interobserver agreement for contrast-enhanced ultrasound (CEUS)-based standardized algorithms for the diagnosis of hepatocellular carcinoma in high-risk patients. Ultraschall Med. 2018;39(6):667-74. Terzi E et al. Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter retrospective study of 1,006 nodules. J Hepatol. 2018;68(3):485-92

Keep your finger on the pulse

Join Now

Elevating the Quality of Healthcare Globally