Hepatocellular carcinoma and liver transplantation: an animal model

The objective of this study was to develop an animal model to evaluate the biology of hepatocellular carcinoma (HCC) recurrence after liver transplantation. HCC was induced in Brown Norway (BN) rats (n = 45) by diet-hylnitrosamine (DEN) administered continuously through the drinking water. Starting from day 14, rats were sequentially autopsied or syngeneically transplanted according to Kamada's cuff technique. After 74 days of DEN administration, neoplastic liver lesions appeared and after a mean of 102 days (SD +/- 6) the animals died of abdominal haemorrhage from liver tumours. At this time lung metastases were present in three-fifths animals. Transplantation success was dependent on the DEN consumption and thereby the tumour stadium. After 74 days of DEN administration BN rats could no longer be transplanted because of anaesthetic problems or technical problems due to tumour adhesion to surrounding tissues. No recurrence was found in the transplants. In conclusion, we believe that timing of the operation in this HCC model is essential because the physical condition of the animals prohibits orthotopic liver transplantation in an advanced tumour stage. With a different DEN dosage scheme this problem may be solved.