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Tumor Lymphocyte Infiltration and Prognosis in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation

Background: Liver transplantation (LT) is an established treatment method in patients with hepatocellular carcinoma (HCC). However, a number of patients experience early recurrence and poor results as a consequence of aggressive tumor biology. Due to the ever increasing organ shortage, new biologic prognostic factors are necessary in order to stratify the patients regarding prognosis. Methods: 44 patients with HCC treated by LT were included in this retrospective study. Analyzed clinical and pathologic data include age, sex, number and size of tumors, tumor differentiation, presence of vascular invasion, adherence to Milan criteria, alpha-fetoprotein level. Immunostaining was used to assess the infiltration of CD3+, CD4+, CD8+ and Foxp3+ cells. Kaplan Meier curves and receiver operator characteristic (ROC) analysis were used to analyze recurrence free and overall survival. Results: Presence of microvascular invasion was found to be associated with HCC recurrence (p=0.035). Analysis of immune parameters showed that the patients with increased total lymphocyte infiltration measured by the number of tumor infiltrating CD3+ cells are less likely to experience recurrence (p=0.05). ROC curve analysis showed that patients with a CD4/CD8 ratio greater than 1 had better chances of recurrence free survival. Also, patients with lower numbers of infiltrating T reg cells were found less likely to experience HCC recurrence (p=0.025). Conclusion: Our results indicate that total lymphocyte infiltration, CD4/CD8 ratio and T reg infiltration have prognostic significance in HCC. These parameters could add valuable information to the presently used morphologic criteria in order to stratify HCC patients who benefit from liver transplantation.

lymphocyte ; hepatocellular carcinoma ; liver transplantation

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