Prediction of Macrotrabecular-Massive Hepatocellular Carcinoma and Associated Prognosis Using Contrast-enhanced US and Clinical Features

Purpose To develop a combined contrast-enhanced US (CEUS) clinical model for the prediction of macrotrabecular-massive hepatocellular carcinoma (MTM HCC) and evaluate its diagnostic and prognostic values. Materials and Methods This secondary analysis of a prospective multicenter study (ClinicalTrials.gov: NCT04682886) included participants from three independent cohorts who underwent CEUS and surgical resection for HCC between January 2017 and December 2022. Two radiologists independently reviewed CEUS data, and the interreader agreement was evaluated. Logistic regression was performed using the training cohort to determine the predictors associated with MTM HCC, while the validation cohort was used to evaluate the diagnostic and prognostic values of the predictors. Results A total of 387 participants (mean age, 55.09 years ± 10.33 [SD]; 342 male) were included. Four clinical and CEUS features were associated with MTM HCC: early washout (before 60 seconds) (odds ratio [OR]: 8.82 [95% CI: 4.22, 18.64], <i>P</i> < .001), hypoenhancing component (OR: 4.03 [95% CI: 1.78, 9.49], <i>P</i> < .001), tumor size (OR: 1.28 [95% CI: 1.04, 1.59], <i>P</i> = .02), and serum α-fetoprotein level greater than 100 ng/mL (OR: 3.01 [95% CI: 1.41, 6.63], <i>P</i> = .004). The combined predictive model yielded an area under the receiver operating characteristic curve of 0.89 (95% CI: 0.85, 0.93) in the training cohort and 0.81 (95% CI: 0.73, 0.89) in the validation cohort. The model also achieved a negative predictive value of 94.2% (147 of 156) in the training cohort and 88.0% (66 of 75) in the validation cohort, with high prognostic accuracy for overall survival (hazard ratio: 2.26 [95% CI: 1.07, 4.79], <i>P</i> = .03). Conclusion The combined CEUS-clinical predictive model could be used to characterize the MTM HCC subtype and determine prognosis. <b>Keywords:</b> Molecular Imaging-Angiogenesis, Ultrasound-Contrast, Liver, Macrotrabecular-Massive Hepatocellular Carcinoma, Contrast-enhanced US Clinical trial registration no. NCT04682886 <i>Supplemental material is available for this article.</i> © RSNA, 2025.