PurposeThis study evaluated the performance of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in patients without LI-RADS-defined hepatocellular carcinoma (HCC) risk factors (RF-).MethodsPatients with LI-RADS-defined HCC risk factors (RF+) and RF- were enrolled in a retrospective study. Additionally, a prospective evaluation in the same centre was performed as a validation set. The diagnostic performances of the CEUS LI-RADS criteria in RF+ and RF- patients were compared.ResultsOverall, we included 873 patients in the analyses. In the retrospective study, the LI-RADS category (LR)-5 specificities for diagnosing HCC did not differ between the RF+ and RF- groups (77.5% [158/204] vs 91.6% [196/214], P = 0.369, respectively). However, the positive predictive value (PPV) of CEUS LR-5 was 95.9% (162/169) and 89.8% (158/176) in the RF+ and RF- groups, respectively (P = 0.029). In the prospective study, the PPV of LR-5 for HCC lesions was significantly higher in the RF+ group than in the RF- group (P = 0.030). The sensitivity and specificity did not differ between the RF+ and RF- groups (P = 0.845 and P = 0.577, respectively).ConclusionsThe CEUS LR-5 criteria shows clinical value for diagnosis of HCC in patients with and without risks.