Published online Jan 15, 2026. doi: 10.4251/wjgo.v18.i1.111144
Revised: July 25, 2025
Accepted: November 18, 2025
Published online: January 15, 2026
Processing time: 198 Days and 20.7 Hours
The treatment technology of liver cancer is progressing. In addition to traditional surgical resection, combined therapies of immunotherapy based on immune checkpoint inhibitors, chemotherapy, and transcatheter arterial chemoembolization for hepatocellular carcinoma are more and more widely used. Accurate preoperative diagnosis of liver cancer will provide important information for comprehensive treatment and prognosis evaluation of liver cancer. Sonazoid-contrast-enhanced ultrasound is not only helpful for the qualitative diagnosis of liver lesions, but also has great potential in the diagnosis of histological differentiation of liver cancer.
To assess the differentiation of hepatocellular carcinoma (HCC) by utilizing the parameters and imaging features of Sonazoid-contrast-enhanced ultrasound (CEUS).
A retrospective analysis was conducted on the CEUS data of 239 lesions through case-control study. These patients received Sonazoid-CEUS within one week before surgery and were confirmed as HCC by postoperative pathology. Within the cases, patients were further categorized into well-differentiated and poorly-differentiated group. Time-intensity curves of the region of interest in both arterial and Kupffer phases were generated, allowing for the acquisition of quantitative parameters to assess the diagnostic efficacy in distinguishing lesions between these two groups and determining an appropriate cut-off value.
Univariate analysis showed that the absolute value of enhancement intensity (EIAV), intensity ratio (IR) and intensity difference (ID) in Kupffer phase were statistically different between the groups with different degree (P = 0.015, P = 0.000, P = 0.000). The sensitivity and specificity were 40.2%, 82.4%, 80.4% and 78.1%, 86.9% and 74.5%, respectively, for differentiating HCC lesions with EIAV ≥ 56.384 dB, IR ≥ 1.215 and ID ≥ 9.184 dB. The area under the receiver operating characteristic curve were 0.590, 0.877, 0.815. There was no significant difference in the parameters of arterial phase, including peak time, initial growth time, rise time and the absolute value of peak intensity of lesions between the two groups (P > 0.05). Multivariate analysis showed that the level of alpha-fetoprotein (AFP) and IR were risk factors for poor differentiation (P = 0.001).
Among the parameters of Sonazoid-CEUS, IR in Kupffer phase exhibits superior diagnostic efficacy with high sensitivity and specificity in the diagnose of pathological differentiation of HCC. Combined with preoperative AFP level, a more accurate diagnosis will be obtained. Compared with portal vein phase, Kupffer phase showed the ability to identify HCC lesions more sensitive. These findings hold significant guiding implications and reference value for clinical practice.
Core Tip: This study used quantitative parameters and imaging characteristics from Sonazoid-contrast-enhanced ultrasound using perfluorobutane microspheres to evaluate the histological differentiation of hepatocellular carcinoma (HCC). Both univariate and multivariate analyses indicated that Kupffer phase parameters, particularly the intensity ratio (IR), outperformed conventional clinical markers. IR proved to be a valuable, non-invasive predictor of tumor differentiation, supporting more informed preoperative decision-making in HCC management. It is simple to calculate, relatively unaffected by variations in hepatic perfusion or fibrosis, and well-suited for routine clinical application. Receiver operating characteristic analysis identified an optimal cut-off value of 1.215 for IR.