Background and Aims: The combination of transarterial chemoembolization (TACE) with molecular targeted therapy and/or immune checkpoint inhibitors (ICIs) has emerged as a cornerstone treatment for intermediate-to-advanced hepatocellular carcinoma (HCC). However, the risk of hepatotoxicity associated with these multimodal regimens remains inadequately characterized. This study aimed to evaluate the incidence, severity, and independent predictors of hepatotoxicity, and to develop a clinically practical prediction model. Materials and Methods: This retrospective study analyzed data from 200 HCC patients treated at Shandong First Medical University Affiliated Cancer Hospital between October 2021 and July 2024. Patients received either TACE plus tyrosine kinase inhibitors (TKIs) (n=120) or TACE plus TKIs and ICIs (n=80). Hepatotoxicity was graded according to CTCAE v5.0 criteria. Multivariate logistic regression was employed to identify independent risk factors and construct a predictive nomogram. Results: The overall hepatotoxicity incidence was 38.00%, predominantly mild-to-moderate (Grade 1: 63.16%; Grade 2: 23.68%; Grade 3: 13.16%). No Grade 4 events occurred, and no significant difference was observed between treatment groups (P=0.637). Multivariate analysis identified four independent predictors: liver cirrhosis (OR=1.684), ALBI Grade 2/3 (OR=6.436), elevated total bilirubin (OR=1.040), and decreased prothrombin activity (OR=0.968). The resulting TCAP (Total bilirubin, Cirrhosis, ALBI grade, Prothrombin activity) nomogram demonstrated robust discriminatory performance (AUC=0.855) with a sensitivity of 82.00% and specificity of 79.10% at the optimal cut-off value of 0.419. Conclusion: The TCAP nomogram provides a reliable, evidence-based tool for individualized hepatotoxicity risk stratification in HCC patients undergoing TACE-based combination therapy. Keywords: hepatocellular carcinoma, transarterial chemoembolization, tyrosine kinase inhibitors, immune checkpoint inhibitors, hepatotoxicity, nomogram
Ma et al. (Sun,) studied this question.