Using Machine Learning to Improve the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System Diagnosis of Hepatocellular Carcinoma in Indeterminate Liver Nodules

Liver cancer ranks among the most lethal cancers. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and better diagnostic tools are needed to diagnose patients at risk. The aim is to develop a machine learning algorithm that enhances the sensitivity and specificity of the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS-LIRADS) in classifying indeterminate at-risk liver nodules (LR-M, LR-3, LR-4) as HCC or non-HCC. Our study includes patients at risk for HCC with untreated indeterminate focal liver observations detected on US or contrast-enhanced CT or MRI performed as part of their clinical standard of care from January 2018 to November 2022. Recursive partitioning was used to improve HCC diagnosis in indeterminate at-risk nodules. Demographics, blood biomarkers, and CEUS imaging features were evaluated as potential predictors for the algorithm to classify nodules as HCC or non-HCC. We evaluated 244 indeterminate liver nodules from 224 patients (mean age 62.9 y). Of the nodules, 73.2% (164/224) were from males. The algorithm was trained on a random 2/3 partition of 163 liver nodules and correctly reclassified more than half of the HCC liver nodules previously categorized as indeterminate in the independent 1/3 test partition of 81 liver nodules, achieving a sensitivity of 56.3% (95% CI: 42.0%, 70.2%) and specificity of 93.9% (95% CI: 84.4%, 100.0%). Machine learning was applied to the multicenter, multinational study of CEUS LI-RADS indeterminate at-risk liver nodules and correctly diagnosed HCC in more than half of the HCC nodules.