The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with “early-stage” HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients. 1. Introduction Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of liver cells [1–3]. Disease burden owing to HCC is significantly increasing in recent years. It is currently the fifth most common cancer and the third most common reason for cancer-related mortality worldwide [1–6]. HCC mainly occurs in a damaged organ; liver cirrhosis as a result of viral hepatitis (hepatitis B virus (HBV) or/and hepatitis C virus infection (HCV)) or chronic alcohol abuse is a major risk factor for development of HCC. The incidence of viral hepatitis is markedly increasing worldwide, which will even enhance the epidemiologic importance of HCC in the near future [7–10]. Continuous clinical surveillance programs in patients with liver cirrhosis were shown to be useful in the detection of HCC at early stages. Recommended surveillance strategies are based on periodic evaluation by ultrasound imaging and determination of blood levels of the tumor marker alpha-fetoprotein (AFP) [11–14]. Suspicious intrahepatic lesions should be further evaluated by advanced imaging techniques such as contrast-enhanced ultrasound and computed
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