Liver allocation for HCC: A moving target

With more than 1,000,000 new cases diagnosed worldwide1 and the incidence rising,2 hepatocellular carcinoma (HCC) has the potential to overwhelm the liver transplant system in very short order. Liver transplantation remains the only curative option for the majority of early stage cases, because the vast majority arise in cirrhotic livers, thereby limiting surgical resection to the few cases where functional hepatic synthetic reserve is sufficient to tolerate removal of hepatic parenchyma. Analyses of results for patients staged by retrospectively determined histologic criteria have indicated that liver transplantation for patients with stage I or stage II disease achieve excellent longterm survival rates3,4 that are equal, or superior,5 to those for patients with nonmalignant indications for transplant. For these reasons, the recent change in US liver allocation policy was designed to assign extra priority for these patients.6 Why was increased priority needed for these cases under the new plan? Many reports have documented increasing “dropout rates” for liver transplant candidates with HCC because of prolonged waiting time for organs.7 Several reports have recently addressed several temporizing treatments or strategies, which although not curative might be helpful in reducing the dropout rate, particularly for those candidates likely to wait more than 1 year on the list.8,9 However, the new allocation plan, based on the model for end-stage liver disease (MELD),10 assigns priority to waiting candidates based on their risk of death within three months. The MELD model alone would not have assigned much priority to candidates with early-stage HCC, because they were not at risk of dying from the cancer anytime soon, and many of these patients do not have severe synthetic liver failure. Therefore, without any additional adjustment in their priority, the new system would have increased the dropout rate for the HCC candidates with early-stage disease. However, using an endpoint other than the risk of death, such as the risk of progression beyond stage II HCC, one could develop an estimated risk of progression that could be equated to the MELD score for HCC candidates.11 The original US MELD-based allocation plan estimated a 15% risk for candidates with stage I disease, and a 30% risk for candidates with stage II disease of progressing beyond stage II. 6 Inherent in any system giving higher priority to a group of candidates is the need to accurately diagnose the condition for which the higher priority is to be granted. This is the beauty of the MELD system. The MELD score has been prospectively validated to accurately predict the risk of death for patients with chronic liver disease. However, no such precise scoring system exists to predict the risk of stage I or II HCC progressing beyond stage II disease. In fact, as has been noted by several authors12,13 and highlighted by the article by Hayashi et al.14 in this issue of Liver Transplantation, the diagnostic accuracy for HCC in cirrhotic patients does not have the same high degree of predictive value. The present authors noted that the rate of transplantation for candidates with HCC increased threefold in the MELD era; however, they did not mention whether they had observed a change in the dropout rate in their cohorts. They found that three of 15 candidates diagnosed as having HCC in the pre-MELD era were falsely diagnosed when the explanted liver specimens were examined after transplant, and five of 15 were falsely diagnosed after the institution of MELD. While this difference was not statistically significant, the authors suggested that more livers were “misallocated” to candidates without HCC in the MELD era at their center. This was mostly because the authors chose to exclude living donor grafts given to recipients diagnosed as having HCC pretransplant but for whom no HCC was found histologically as having the graft “misallocated. ” One could argue that misallocating a living donor organ to a candidate thought to have HCC who ultimately didn’t is just as significant as “misallocating” a deceased donor organ to such a recipient. Another difficulty with this study is the small samples sizes, a problem that limits many studies of liver