Kupffer-phase Sonazoid ultrasound LI-RADS for liver cancer: diagnostic performance and algorithm modification

This study aimed to enhance the noninvasive identification of hepatocellular carcinoma (HCC) by modifying the Sonazoid-based contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) through integration of Kupffer-phase (KP) imaging and optimization of washout timing criteria.

This retrospective two-center study enrolled 558 patients with solitary liver nodules who underwent Sonazoid-based CEUS between August 2022 and September 2024. CEUS features were assessed according to LI-RADS v2017 using predefined washout time windows (2, 5, and 10 minutes). A modified LI-RADS algorithm incorporating KP hypoenhancement was developed. Interobserver agreement was evaluated using the Cohen kappa. Diagnostic performance metrics (area under the curve [AUC], sensitivity, specificity, and positive predictive value) were compared between the modified CEUS LI-RADS algorithms and the Japan Society of Hepatology (JSH) and Korean Liver Cancer Association (KLCA) guidelines using the McNemar and DeLong tests.

For key CEUS features, interobserver agreement was moderate to almost perfect (κ=0.580-0.815). The modified CEUS LI-RADS-10min algorithm demonstrated superior performance over the other algorithms. By reclassifying LR-M nodules with early washout and mild KP hypoenhancement as LR-5, the modified CEUS LI-RADS-10min algorithm achieved the highest diagnostic performance for HCC (AUC, 0.782), improving sensitivity while maintaining specificity (73.7%). Its performance was comparable to that of the KLCA guideline. The JSH guidelines showed the highest sensitivity (91.7%) but the lowest specificity (53.9%).

Integrating KP hypoenhancement with a 10-minute washout window improves the sensitivity of Sonazoid-based CEUS LI-RADS for diagnosing HCC while preserving specificity, providing feasible refinement aligned with established guidelines and promoting standardization.