Recurrence of Hepatocellular Carcinoma Following Liver Transplantation Within Milan Criteria

Abstract

The optimal curative options for the management of hepatocellular carcinoma (HCC) are surgical resection and/or liver transplantation (LT). Recent data suggest that ablative treatment such as radio frequency ablation (RFA) may be comparable to surgical resection for small tumors. The 5-year tumor-free survival after surgical resection (or RFA) is less than LT irrespective of the risk factor for HCC. LT is considered the best option in people with HCC and portal hypertension, or those with advanced cirrhosis because of lower surgical mortality rates. Prior to the introduction of Milan criteria, the long-term results of liver transplantation in patients with hepatocellular carcinoma have been variable and disappointing, with an overall 5-year survival rate ranging from 30 to 40 %. Application of Milan criteria has reduced tumor recurrence rates to ~10 % and has improved 5-year tumor-free survival (~70 %). The UNOS data also suggested that the survival improved after the publication of Milan criteria in the United States. There is an ongoing debate whether Milan criteria could be expanded without having an adverse effect on tumor-free survival. Published studies suggest that HCC patients transplanted outside the Milan criteria have 5-year survival rates between 46 and 60 %. One of the major criticisms of Milan criteria is that it is based on pre-LT imaging findings, and only 70 % of explant pathology findings correlate with imaging. Moreover, imaging techniques, protocols, and interpretations of images are not uniform, and additionally, Milan criteria do not take into consideration the variability of tumor biology. As we understand the variability of HCC tumor biology better and develop reliable molecular markers, we may be able to redefine the LT selection criteria for patients with HCC without any negative effects of outcomes. Until then, Milan criteria appear to be a reasonable benchmark for selecting HCC patients for LT.