Purpose:
To evaluate the performance of a combined clinical-radiomics model using multiple machine learning approaches for predicting pathological differentiation in hepatocellular carcinoma (HCC).

Material and methods:
A total of 196 patients with pathologically confirmed HCC, who underwent preoperative computed tomography (CT) were retrospectively enrolled (training: n = 156; validation: n = 40). The modelling process included the folowing: (1) clinical model construction through logistic regression analysis of risk factors; (2) radio­mics model development by comparing 6 machine learning classifiers; and (3) integration of optimal clinical and radiomic features into a combined model. Model performance was assessed using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). A nomogram was constructed for clinical implementation.

Results:
Two clinical risk factors (BMI and CA153) were identified as independent predictors of differentiated HCC. The clinical model showed moderate performance (AUC: training = 0.705, validation = 0.658). The radiomics model demonstrated improved prediction capability (AUC: training = 0.840, validation = 0.716). The combined model achieved the best performance in differentiating HCC pathological grades (AUC: training = 0.878, validation = 0.747).

Conclusions:
The integration of CT radiomics features with clinical parameters through machine learning provides a promising non-invasive approach for predicting HCC pathological differentiation. This combined model could serve as a valuable tool for preoperative treatment planning.