Role of Circulating Tumour Cells in the Management of the Liver Transplant Patient with Hepatocellular Carcinoma.

Introduction: For hepatocellular carcinoma (HCC), liver transplantation (LT) is considered a curative treatment, however, more than 10% of transplant recipients have recurrences within the first year. This suggests the existence of circulating-tumor-cells (CTC) that spread from a primary tumor and travel to peripheral blood and distant organs. Their detection and monitoring could be of great clinical value to an early prediction of recurrence as a real-time liquid biopsy. The aim of this study is to determine the relationship between CTC and clinicopathological variables and to compare the CTC-levels in patients with HCC before transplantation and at one and two years after surgery. Methods: Peripheral blood was obtained from 34 patients with HCC included in the LT list. Immunomagnetic isolation of CTC was performed by the IsoFlux® System. Cell enrichment was stained with anti-CK, Hoechst-33342 and antiCD45, performing cell counting under a fluorescence microscope. The clinicopathological variables (number of tumors, vascular invasion, tumor necrosis and recurrence) were collected. Spearman’s rho, Mann-Whitney and Wilcoxon test were used. Results: We found statistically significant differences in the CTC-levels between patients with vascular invasion and those without (U=0; p=0.005) such that patients with vascular invasion had median levels of 539 CTC/10 mL (IR: 448-1768) and those without vascular invasion had median levels of 3 CTC/10 mL (IR:0- 31.25). Also we found a statistically significant decrease in post-transplant CTC-values at one year (Z= -2.672/ p=0.008) and two years (Z= -2.218/ p=0.027). Conclusions: The median CTC-levels of the patients included in the study showed a downward trend after liver transplantation. Also, a significant difference was found in the levels of pre-transplant-CTC between patients with and without vascular invasion, these levels being significantly higher in patients with vascular invasion compared to those without vascular invasion. Detection of CTC may have a useful clinical implication in predicting the evolution of HCC after LT.