Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation

Background/Aims: Liver transplantation is an effective treatment for highly selected patients with hepatocellular carcinoma (HCC), but tumour recurrence remains an important cause of mortality. There are few data on the relation between the recurrence of HCC and lymphocytic infiltration following liver transplantation. Methods: The tumour CD4 ⁺, CD8 ⁺, CD25 ⁺ and Foxp3 ⁺ lymphocyte infiltrate was assessed by immunohistochemistry in explant tissue of 69 patients who underwent liver transplantation for HCC between 1985 and 2001. The data were analysed according to HCC recurrence and factors known to be associated with outcome. Results: Tumour size (Hazard ratio (95% CI: 1.19 (1.02, 1.39), P = 0.03)), vascular invasion (P = 0.02), lymphocyte infiltration (P = 0.02) and CD4:CD8 ratio (P = 0.001) were identified as significant univariate predictors of tumour recurrence. On multivariate analysis CD4:8 ratio (P = 0.001), vascular invasion (P = 0.01), tumour size (P = 0.06) and reduced lymphocyte infiltration (P = 0.03) were significant independent predictors of recurrence. The presence of Foxp3 ⁺ T-lymphocytes was not predictive of recurrence, but was associated with vascular invasion (FE = 9.02, P = 0.04). Conclusions: The data support the hypothesis that immune responses are important in HCC and that the phenotype of infiltrating lymphocytes is informative regarding prognosis.