Matrix Metalloproteinase 1 as a Novel Biomarker for Monitoring Hepatocellular Carcinoma in Liver Transplant Patients.

INTRODUCTION: Orthotopic liver transplantation (LT) is considered to be one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). Alfa-fetoprotein (AFP) is the most-used biomarker for HCC despite low sensitivity and specificity. Matrix metalloproteinase 1 (MMP-1) has been considered to be involved in the process of vascular invasion of the malignant cells. The objective of this study was to assess the use of MMP-1 for the management of HCC patients for LT. METHODS: Levels in serum of MMP-1 (ng/mL) and AFP (ng/mL) were assessed in 20 HCC patients (Milan criteria) before and 1, 6, and 12 months after LT. RESULTS: There was a strong significant correlation between levels of MMP-1 and levels of AFP (ρ = .954; P ≤ .05). There were statistical differences in the levels of MMP-1 and APF between the pre-transplantation and post-transplantation groups (1 and 12 months). Increments of both markers 6 months after LT compared with the levels 1 month after LT were detected in 4 of the 20 HCC patients. The detection of recurrence by means of imaging was coincident with the increment of both markers 6 months after LT in 3 of those 4 patients. CONCLUSIONS: After 12 months of follow-up, levels of MMP-1 were comparable to AFP levels after LT. Levels of both markers increase 6 months after LT in patients showing recurrence, indicating discriminatory power to predict relapse and thus serving as valuable markers for HCC monitoring. MMP-1 could be useful in the management of HCC after LT.

Oncological Evaluation by Positron-emission Tomography, Circulating Tumor Cells and Alpha Fetoprotein in Patients With Hepatocellular Carcinoma on the Waiting List for Liver Transplantation.

INTRODUCTION: The objectives of this study are the determination of the number of circulating tumor cells (CTCs), by means of the IsoFlux enrichment system (Fluxion Biosciences Inc, San Francisco, California, United States) in patients with hepatocellular carcinoma (HCC) in compliance with the Milan criteria and on the waiting list for hepatic transplantation, as well as the study of its relation with the of α-fetoprotein levels (AFP) and positron-emission tomography-computed tomography (PET-CT) findings. PATIENTS AND METHODS: An oncologycal evaluation with PET-CT, CTCs, and AFP was conducted in 24 consecutive patients with HCC eligible for orthotopic liver transplantation according to the Milan criteria. The diagnosis of HCC was made according to clinical, biological, and radiological findings. RESULTS: We detected CTCs in peripheral blood in 21 of 24 patients (87.5%) before liver transplantation, with a mean number CTCs of 156 ± 370 (range, 2 to 1768) with statistically significant association between number of CTCs detected in peripheral blood and the time within the waiting list (P < .05), but not betwen AFP levels and standard uptake value and time to orthotopic liver transplantation (P > .05). CONCLUSIONS: PET-TC, CTCs, and AFP levels could be an essential key for the correct management of the patients with HCC on the waiting list for liver transplantation.

Comparison of Two Types of Liquid Biopsies in Patients With Hepatocellular Carcinoma Awaiting Orthotopic Liver Transplantation.

INTRODUCTION: Orthotopic liver transplantation (OLT) is considered one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). It has been shown that more than 10% of transplanted individuals suffer relapse during the first year after surgery and most of them die because of the tumor. The circulating tumor cells (CTCs) are the main source of recurrences as they disseminate from a primary or metastatic tumor lesion through peripheral blood. We aimed to determine the concentration of CTCs in peripheral blood in these patients by 2 different approaches: the CellSearch and the IsoFlux systems to assess their applicability to this disease monitoring. PATIENTS AND METHODS: A comparative study was conducted in 21 patients with HCC eligible for liver transplantation according to the Milan criteria, whose peripheral blood was processed by the CellSearch and the IsoFlux systems. RESULTS: CTCs were isolated in 1 of the 21 patients (4.7%) by the CellSearch system and in 19 of the 21 patients (90.5%) by the IsoFlux method. The comparison of both methods using Bland-Altman plot shows that there is not consistency in the determination of CTCs in our patients, finding a proportional bias between them. CONCLUSION: The results obtained by both CTCs isolation systems are not interchangeable nor transferable. The CellSearch system does not seem to be the ideal approach for studying CTCs in patients with HCC. The IsoFlux system displays greater sensitivity in the identification of CTCs and might become an important tool in patient management.