Peripheral blood CD4(+) cell ATP activity measurement to predict HCC recurrence post-DCD liver transplant

摘要

Background and Aim: Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4(+) adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post-OLT. Methods: A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6-36 months post-OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time. Results: Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post-OLT, and the average ImmuKnow assay in these patients was 190 +/- 48 ng/ml, which was less (p < 0.05) than in patients without HCC recurrence, whose average ATP level was 313 +/- 90 ng/ml. ATP levels post-OLT were found to be significantly associated with the risk of tumour recurrence. The ratio of T reg cells and the levels of TGFb and IL-10 were higher in recurrence patients than in recurrence-free patients. Conclusion: Greater suppression of cellular immunity, as measured by the ImmuKnow assay, was associated with progression of HCC recurrence post-OLT. ImmuKnow assay was helpful in determining the risk of early recurrence of HCC postliver transplant. A pathway consisting of T reg cells, TGF beta and IL-10 might be the HCC recurrence-predominant pathway.