Clinical impact of contrast-enhanced ultrasound on indeterminate or non-characterizable liver nodules on CT/MRI: sub-analysis from a prospective multicenter trial

Introduction The present retrospective study of prospectively collected cases aimed to investigate the clinical utility of CEUS for HCC diagnosis in cases where liver lesions were indeterminate at intermediate risk (corresponding to LR3 class) or non-characterizable (LR-NC class) on computed tomography (CT) or magnetic resonance imaging (MRI), conditions for which AASLD and EASL guidelines recommend CEUS despite the lack of prospective studies. Methods A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) enrolled 646 patients with at least one (<5cm) lesion at risk for HCC between January 2018 and August 2021. CEUS was performed using Sonovue/Lumason (Bracco Diagnostic) within 4 weeks of CT/MRI. Tissue histology or 12 months follow-up CT/MRI imaging results were used as the reference standard in the respective preferential order. The current study focused on the diagnostic performance of CEUS for HCC diagnosis in masses classified as LR-3 or LR-NC. Results Within the original dataset, 75 nodules were classified as LR-3 (n=54) or non-characterizable (LR-NC, n=21) on CT/MRI. Among LR-3, 25.9% (14/54) were confirmed as HCC, 72.2% (39/54) non-malignant, and 1.9% (1/54) non-hepatocellular malignancy. CEUS LR-1 and LR-2 lesions (13.0%, 7/54) were confirmed as non-malignant, while all LR-5 (13.0%, 7/54) as HCC. Accordingly, the use of CEUS LI-RADS following LR-3 CT/MRI classification resulted in a conclusive diagnosis in 30.7% of previously indeterminate cases. Of 21 nodules initially classified as LR-NC on CT/MRI, final diagnosis was 52.4% HCC (11/21), 42.8% non-malignant nodules (9/21), and 4.8% other malignancies (LR-M) (1/21). CEUS LR-1 (n=1), LR-5 (n=6) and LR-M (n=2) were confirmed as benign, HCC, and other malignancies, respectively. Accordingly, CEUS LI-RADS showed a clinical impact of 42.9% of previously indeerminate cases. Conclusion CEUS LI-RADS demonstrated high clinical impact in liver nodules with indeterminate CT/MRI characterization, validating the recommendations for its use in this setting.