HCC is the most studied primary tumor entity for the indication of liver transplantation. Because of the gap between the numbers of suitable donors and those of patients on the waiting list, transplantation should only be performed in patients who benefit most from organ transplantation. These patients can only be identified by clear guidelines and objective scoring systems.
The MC are widely used for the selection of patients and are also embedded in the MELD-based organ allocation programs in 1,2. Patients beyond the MC can be transplanted based on extended allocation policies 9,10. However, the limit for the exclusion of patients with advanced tumors from liver transplantation should be defined since the increase in tumor burden is related to a poor prognosis following transplantation 11,12.
The current practice to prove the LTx indication is based on radiological findings such as tumor diameter and number of hepatic nodules. However, the accuracy of pretransplant imaging in cirrhotic liver has been questioned in several studies when compared with posttransplant histopathology 13,8.
To avoid these problems and to determine the real tumor load at the time of LTx, we analyzed our patients based on histopathological results. Then, we retrospectively classified the patients into established indication criteria for patients with HCC and assessed postoperative survival.
In the same manner, Lee et al. investigated the basic histopathological features of patients with HCC in living donor liver transplantation and introduced the so-called Asan criteria. Meeting the Asan criteria (largest tumor diameter ≤5 cm, number of tumors ≤6), they could achieve a 5-year overall survival of 76.3%, which was not significantly higher than the 5-year survival if meeting the MC in their population.
In our patients, who were transplanted following deceased donation, we observed similar survival curves for the patients fulfilling the MC or UTS or Asan criteria. Current data on the outcome of patients fulfilling the MC show overall 1-, 3- and 5-year survival rates of 85-93%, 75-81%, and 68-73%, respectively 14,15. Our data were comparable to international data showing 1-, 3- and 5-year overall survival rates of 82%, 77%, and 69%, respectively, within the MC. Using extension criteria such as the AFP score, UTS and Asan, we were able to show similar results 16,8,6,17.
Interestingly, in our study, patients with an AFP score equal to or less than 2 showed a 5-year survival rate of 52%, a significantly worse long-term survival compared to patients in other groups. This difference is most likely due to the missing AFP data of 15 patients, and consequently reduced statistical power.
An independent factor influencing postoperative survival after transplantation is the recurrence of HCC. In our analysis, HCC recurrence occurred after a median follow-up period of 28 months after transplantation. All of these patients died during the follow-up period. The univariate analysis determined a significant influence of the AFP level, number of tumors, maximum diameter of the largest tumor and tumor grade on the outcome after LTx.
Whether AFP is a reliable marker is still an ongoing topic, and the cutoff AFP level as a contraindication for LTx has not been determined[i]. In our study, only 21 patients with a maximum AFP level higher than 100 ng/ml and only ten patients with an AFP level higher than 500 ng/ml were transplanted, showing no unique survival or recurrence features (data not shown). Thus, we cannot assess a cutoff AFP level for contraindication for LTx in concordance with the current guidelines 5.
In our detection of HCC recurrence, established clinical scores, such as the MC, UTS criteria, Asan criteria and AFP score, showed similar prediction for HCC recurrence following LTx. Concerning the two endpoint parameters together (overall survival and recurrence), the best performance with sensitivity and specificity was achieved when considering the UTS criteria.
Using UTS as the extension criteria for LTx, we could add 12 patients fulfilling UTS, which were beyond the MC and were theoretically excluded from regular allocation policy. Interestingly, the patients fulfilling the UTS but exceeding the MC in our population showed similar survival and recurrence rates compared to the patients fulfilling MC only. Thus, the extension of the MC using the UTS criteria for the indication for LTx must be considered in standard care.
The most important limitation of this study is its retrospective design. Secondly the preoperative imaging techniques during the entire study period (1993 until 2012) was not exactly comparable. However, the sensitivity of preoperative imaging for focal lesions in cirrhotic tissue is still limited 18. The consideration of tumor biology and the underlying disease need to be included in the indication for LTx. New strategies, such as the detection of biomarkers in tumor tissue as well as in the sera of patients with HCC, could help identify new parameters for an indication for LTx in patients with HCC 19,20.