Liver transplantation for hepatocellular carcinoma: role of inflammatory and immunological state on recurrence and prognosis

Criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) and post-LT indicators of prognosis are historically based on the measurement of the tumor mass. Recently, high throughput technologies have increased the prediction of recurrence, but these tools are not yet routinely available. The interaction between HCC and the immune system has revealed an imbalance of lymphocyte phenotypes in the peritumoral tissue, and the increase of regulatory T cells with respect to cytotoxic lymphocytes has been linked to a higher rate of post-LT HCC recurrence. Moreover, some inflammatory markers have shown good reliability in predicting cancer reappearance after surgery, as a result of either a systemic inflammatory response or a decreased capacity of the organism to control the tumor growth. Among these markers, the neutrophil-to-lymphocyte ratio appears to be the most promising and easily available serum parameter able to predict HCC recurrence after LT and following other types of treatment, although the exact mechanisms determining its elevation have not been clarified. Post-LT immunosuppression may impact on cancer control, and the exposure to high levels of calcineurin inhibitors or other immunosuppressants has recently emerged as a negative prognostic factor for HCC recurrence and patient survival. Despite the absence of prospective randomized trials, inhibitors of the mammalian target of rapamycin have been shown to be associated with lower rates of tumor recurrence compared to other immunosuppressors, suggesting their use especially in patients with HCC exceeding the conventional indication criteria for LT.