Effect of Systemic Cyclosporine on Tumor Recurrence After Liver Transplantation in a Model of Hepatocellular Carcinoma

Background: Long-term results after liver transplantation for hepatocellular carcinoma have been disappointing, largely because of the high recurrence rate. It is controversial whether the immunosuppressed state of the recipient contributes to this recurrence rate. We have developed a model in the rat system to examine the effect of immunosuppression on tumor recurrence after transplantation, as well as to evaluate other treatment strategies to decrease the recurrence rate.

Methods: A 2-mm3 nodule of Morris hepatoma 3924a was implanted intrahepatically at day 0. At postimplant day 16, the animals underwent syngeneic orthotopic liver transplantation. Two treatment groups were established. Group I received saline injections subcutaneously for 2 weeks, while group II received subcutaneous cyclosporine injections at 3 mg/kg/day for 14 days. Animal survival, tumor recurrence rate, and sites of recurrence and number of pulmonary nodules were recorded.

Results: Overall survival rate was reduced in animals receiving cyclosporine. The mean survival time was 74.4 days (SEM 6.39 days) in saline-treated animals and 50.4 days (SEM 7.63 days) in the cyclosporine-treated animals. The proportion surviving in group 1 was 47% and in group 2 was 18%. This difference in survival was statistically significant (P=0.025). The incidence of pulmonary nodules was increased in the cyclosporine-treated animals, and tumor recurrence in extrapulmonary sites was seen only in the cyclosporine-treated animals.

Conclusion: Results from this study suggest that cyclosporine has an adverse effect on tumor recurrence after transplantation. This model will be useful to further examine treatment strategies to improve the outcome of transplantation for hepatocellular carcinoma.