How to characterize non‐hypervascular hepatic nodules on contrast‐enhanced computed tomography in chronic liver disease: Feasibility of contrast‐enhanced ultrasound with a microbubble contrast agent

Background and Aim:  Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. Methods:  The subject was 41 hepatic nodules (<30 mm, 18.5 ± 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. Results:  Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. Conclusion:  CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.