Hepatocellular carcinoma (HCC) has a high recurrence rate even after curative hepatectomy. Circulating tumor cells (CTCs) have emerged as promising liquid biopsy biomarkers for minimal residual disease and early recurrence. This study evaluated longitudinal CTC dynamics and their prognostic significance in HCC patients undergoing curative resection.

We prospectively analyzed CTCs in 27 HCC patients at four time points: preoperatively, immediately postoperatively, and at 6 and 12 months after surgery. CTCs were defined as CD45⁻/CD146⁺/ASGPR⁺ using multicolor flow cytometry and immunofluorescence. Recurrence-free survival (RFS) and overall survival (OS) were assessed during a median 3.7-year follow-up. Control groups included 29 patients with non-malignant or non-HCC liver tumors and 8 healthy donors.

Preoperative CTCs were detected in 48.2% of HCC patients (mean 0.46 cells/mL). Detection rates rose to 95% at 6 months and 100% at 12 months post-surgery. Persistent or rising postoperative CTCs were strongly associated with early recurrence (51.8% overall) and reduced RFS (p = 0.02) and OS (p = 0.05). No significant correlation was observed between CTC levels and tumor size or volume, AFP, or IL-6 levels.

Longitudinal CTC monitoring provides an early and non-invasive indicator of recurrence risk and survival after curative HCC resection. Persistent CTCs may represent minimal residual disease and a potential therapeutic target for improving long-term outcomes.