Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after curative resection remains a critical challenge that significantly compromises long-term survival. This study aimed to develop a novel blood-based prognostic scoring system integrating circulating tumor cells (CTCs) and aspartate aminotransferase-to-lymphocyte ratio index (ALRI) for predicting postoperative HCC recurrence. METHODS: This retrospective study enrolled 160 HCC patients undergoing curative resection between January 2019 and July 2023. CTCs were detected using the Cyttel method with immunomagnetic bead negative enrichment combined with immunofluorescence in situ hybridization. COX regression identified independent factors for recurrence-free survival (RFS). Patients were stratified into three groups (CTC-ALRI scores 0, 1, 2) based on preoperative CTC status and ALRI levels. Prognostic performance was evaluated using Kaplan-Meier analysis, Cox regression, logistic regression, receiver operating characteristic curves and time-independent C-index. RESULTS: Multivariate Cox regression identified baseline ALRI and CTC as independent predictors of RFS and were used to develop the CTC-ALRI score. Recurrence rates increased progressively across score groups: 24.00% (score 0), 52.11% (score 1), and 84.38% (score 2) (P<0.001). Median RFS exhibited a stepwise decrease corresponding to increasing CTC-ALRI scores: not reached in the score 0 group, 39.2 months in the score 1 group, and 9.2 months in the score 2 group (log-rank P<0.001). Both Cox regression and logistic regression analyses confirmed the CTC-ALRI score as an independent predictor of RFS and HCC recurrence. The CTC-ALRI score demonstrated excellent predictive performance for both intrahepatic and extrahepatic recurrence, as well as for early and late recurrence. Furthermore, the CTC-ALRI score outperformed conventional factors (AFP, tumor size) and established models (BCLC, TNM, ERASL, SSCLIP, Korean), with areas under the curve of 0.725 and 0.729 for one- and two-year recurrence prediction. Higher scores correlated significantly with Ki-67 proliferation index (P<0.05), providing biological validation. CONCLUSIONS: The preoperative CTC-ALRI score provides superior predictive accuracy for HCC recurrence following curative resection. This accessible, cost-effective biomarker enables refined risk stratification and may guide personalized surveillance and adjuvant treatment strategies.