Liver Transplantation for Hepatocellular Carcinoma Beyond the Milan Criteria

Hepatocellular carcinoma is the most common primary liver malignancy. Liver transplantation has been a successful therapy for selected patients with hepatocellular carcinoma. Since 1996, Milan criteria have been universally recognized as the guidelines for selecting patients with hepatocellular carcinoma for orthotopic liver transplantation. However, the simple use of tumor size and number has been insufficient to indicate the biologic features of hepatocellular carcinoma and to predict the risk of tumor recurrence. The Milan criteria are quite strict because their rules can cause patients to be excluded from wait lists who could in fact benefit from transplant. Therefore, many expanded criteria are now incorporating different biologic markers, such as alpha-fetoprotein. 18F-fluorodeoxyglucose positron emission tomography-computed tomography could be a helpful diagnostic tool to decide the most suitable therapy, particularly for patients with hepatocellular carcinoma beyond the Milan criteria. Patients initially beyond Milan criteria can be downstaged to reduce tumor size to fulfill Milan criteria. Locoregional therapies are used for downstaging, including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. Good responses to downstaging therapy and then waiting at least 3 months after locoregional therapy to reevaluate the decision of liver transplantation for patients with hepatocellular carcinoma beyond Milan criteria can result in better survival rates in these patients. Sorafenib and mammalian target of rapamycin inhibitors are promising agents for reducing tumor recurrence rate after liver transplantation. With cautious patient selection criteria and the use of locoregional therapy before liver transplantation, good results can be obtained for patients beyond Milan criteria who had no better chance other than liver transplant.